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pubmed_969_8868 | Excitatory amino acid stimulation of phosphatidylinositol (PI) hydrolysis has been associated with development of the CNS. Normally minimally ineffective in stimulating PI hydrolysis in the neonatal rat cerebellum, N-methyl-D-aspartate (NMDA) increased levels of PI hydrolysis 82.3 +/- 5.5% above basal values in the presence of 1 microM baclofen, a gamma-aminobutyric acidB (GABAB) receptor agonist. This effect was observed at day 7 but not in adult cerebellum. The effect of baclofen could be mimicked by low dose GABA and taurine, actions which were blocked by prior application of a specific GABAB antagonist. Therefore, the ability of NMDA to stimulate PI hydrolysis in neonatal cerebellar tissue may be regulated by the degree of GABAB receptor stimulation. | 10.1016/0304-3940(91)90433-t |
pubmed_1070_11908 | Ankylosing spondylitis (AS) is characterized by two key pathologic findings: sacroiliac joint and spinal inflammation and new bone formation with possible bone fusion, usually in the axial skeleton. Thus, structural damage in AS must be viewed differently than that in rheumatoid arthritis. Tumor necrosis factor blockers effectively inhibit inflammation, as shown by signs and symptoms, function, C-reactive protein, and MRI, and will probably prevent erosive structural damage. However, the ossification of already-damaged bone cannot be influenced by tumor necrosis factor blockade, because these drugs do not inhibit osteoblasts. It remains to be seen whether additional targeting of new bone formation is clinically meaningful in advanced AS. The most important action to prevent structural damage is probably an early diagnosis and effective anti-inflammatory treatment of AS. | 10.1007/s11926-008-0058-x |
pubmed_83_9485 | Tricellulin is a tight‑junction transmembrane protein that regulates cell‑cell interactions. Altered tricellulin expression could promote tumor cell invasions and metastasis in human cancers. The present study assessed tricellulin expression in colorectal cancer tissues for any association with clinicopathological features of colorectal cancer patients and then investigated the underlying molecular events using quantitative proteomic analysis and in vitro experiments. Tissue samples from 98 colorectal cancer patients and 15 volunteers were collected for immunohistochemistry. Colorectal cell lines were used to overexpress or knockdown tricellulin expression in various assays. The data revealed that upregulated tricellulin expression was associated with lymph node and distant metastases and poor prognosis, while tricellulin overexpression promoted colorectal cancer cell migration and invasion in vitro. In contrast, tricellulin knockdown had positive effects on the tumor cells. Furthermore, TMT‑LC‑MS/MS and bioinformatics analyses revealed that tricellulin was involved in EMT and reduction of apoptosis through the NF‑κB signaling pathway. These findings highlight for the first time the significance of tricellulin in colorectal cancer development and progression. Further study may validate tricellulin as a novel biomarker and target for colorectal cancer. | 10.3892/or.2020.7773 |
pubmed_428_14124 | Severe aplastic anemia (SAA) is an autoimmune disease characterized by severe pancytopenia and bone marrow failure. In our previous studies, we found natural killer (NK) cells were aberrant in SAA patients. T cell immunoglobulin mucin-3 (TIM-3), an important regulator of immunity, is widely detected on NK cells and may contribute as a marker of activation and maturation of NK cells. In this study, we found that SAA untreated patients had lower TIM-3 expression on NK cells and CD56dim NK subsets compared with normal controls, and were correlated with the severity of pancytopenia of SAA. After immunosuppressive therapy (IST), TIM-3 expression recovered to normal level. Moreover, the TIM-3 mRNA levels in NK cells significantly increased in SAA remission patients after IST. We inferred that low expression of TIM-3 on NK cells might lead to NK cells dysfunction and involve in the progress of bone marrow failure in SAA. | 10.1016/j.cellimm.2017.03.003 |
pubmed_901_5348 | Evidence was obtained by the use of alternate semithin-thin serial secretions for light and electron microsocpy that the I cell is the source of CCK PZ. The antibodies used were raised to a synthetic fragment of the mid part (9-20) of the (1-33) CCK-PZ molecule, and were thus free from any contamination with cross-reacting subpopulations of antibodies that might bind to gastrin. | 10.1136/gut.19.5.403 |
pubmed_862_11335 | This article provides an overview of the methods used for optical surface imaging during the last 30 years, with the primary focus on the imaging of the unsedated child. The goal is to provide the reader with an overview of the working methods behind the published articles. This will enable the reader to better interpret current data and decide if a certain approach is suitable for their particular research question. | 10.1097/SCS.0b013e31811ec20a |
pubmed_1042_17844 | Transcription-coupled repair (TCR) removes DNA lesions from the transcribed strand of active genes. Stalling of RNA polymerase II (RNAPII) at DNA lesions initiates TCR through the recruitment of the CSB and CSA proteins. The full repertoire of proteins required for human TCR - particularly in a chromatin context - remains to be determined. Studies in mice have revealed that the nucleosome-binding protein HMGN1 is required to enhance the repair of UV-induced lesions in transcribed genes. However, whether HMGN1 is required for human TCR remains unaddressed. Here, we show that knockout or knockdown of HMGN1, either alone or in combination with HMGN2, does not render human cells sensitive to UV light or Illudin S-induced transcription-blocking DNA lesions. Moreover, transcription restart after UV irradiation was not impaired in HMGN-deficient cells. In contrast, TCR-deficient cells were highly sensitive to DNA damage and failed to restart transcription. Furthermore, GFP-tagged HMGN1 was not recruited to sites of UV-induced DNA damage under conditions where GFP-CSB readily accumulated. In line with this, HMGN1 did not associate with the TCR complex, nor did TCR proteins require HMGN1 to associate with DNA damage-stalled RNAPII. Together, our findings suggest that HMGN1 and HMGN2 are not required for human TCR. | 10.1038/s41598-020-61243-4 |
pubmed_362_12277 | The full-span log-linear (FSLL) model introduced in this letter is considered an nth order Boltzmann machine, where n is the number of all variables in the target system. Let X=(X0,…,Xn-1) be finite discrete random variables that can take |X|=|X0|…|Xn-1| different values. The FSLL model has |X|-1 parameters and can represent arbitrary positive distributions of X. The FSLL model is a highest-order Boltzmann machine; nevertheless, we can compute the dual parameter of the model distribution, which plays important roles in exponential families in O(|X|log|X|) time. Furthermore, using properties of the dual parameters of the FSLL model, we can construct an efficient learning algorithm. The FSLL model is limited to small probabilistic models up to |X|≈225; however, in this problem domain, the FSLL model flexibly fits various true distributions underlying the training data without any hyperparameter tuning. The experiments showed that the FSLL successfully learned six training data sets such that |X|=220 within 1 minute with a laptop PC. | 10.1162/neco_a_01496 |
pubmed_87_8391 | BACKGROUND
Thymic stromal lymphopoietin (TSLP) controls allergic TH2 inflammatory responses through induction of distinct activation programs in dendritic cells (DCs). However, knowledge about TSLP receptor expression and functional consequences of receptor activation by DCs residing in the human respiratory tract is limited.
OBJECTIVE
We wanted to identify TSLP-responding DC populations in the human upper airway mucosa and assess the TSLP-mediated effects on such DCs in allergic airway responses.
RESULTS
We found that the TSLP receptor was constitutively and preferentially expressed by myeloid CD1c(+) DCs in the human airway mucosa and that the density of this DC subset in nasal mucosa increased significantly after in vivo allergen challenge of patients with allergic rhinitis. In vitro, TSLP strongly enhanced the capacity of CD1c(+) DCs to activate allergen-specific memory CD4(+) T cells. Moreover, TSLP rapidly induced CCR7 expression on CD1c(+) DCs. However, TH2 cytokines attenuated TSLP-mediated CCR7 induction, thus inhibiting the TSLP-induced DC migration potential to the draining lymph nodes.
CONCLUSION
Our results suggest that TSLP-mediated activation of human nasal mucosal CD1c(+) DCs triggers CCR7-dependent migration to the draining lymph nodes and enhances their capacity to initiate TH2 responses. However, the observation that TH2 cytokines abrogate the induction of CCR7 implies that during a TH2-mediated inflammatory reaction, TLSP-activated CD1c(+) DCs are retained in the inflamed tissue to further exacerbate local inflammation by activating local antigen-specific memory TH2 cells. | pubmed_87_8391 |
pubmed_810_10544 | OBJECTIVE
To investigate the safety and effectiveness of one-stage posterior correction of scoliosis associated with little symptomatic syringomyelia.
METHODS
A total of 19 cases diagnosed as scoliosis with little symptomatic syringomyelia between January 2003 and November 2010 were included in this study (study group), the patients underwent one-stage posterior correction and instrumentation without neurosurgery for the syringomyelia. At the same time, 9 cases with severe symptomatic syringomyelia were included as the control group, the patients underwent neurosurgery before scoliosis correction, including suboccipital decompression and syrinx shunting. All patients underwent posterior pedicle screw or screw-hook hybrid instrumentation. The preoperative, postoperative and the last follow-up of the Cobb angle of the coronal main curve and thoracic kyphosis were measured. Also, the preoperative and postoperative of the apical vertebra translation, apical vertebra rotation and trunk shift were measured by the same person. The perioperative and the last follow-up complications of neurological injury were recorded. The surgical outcome and postoperative complications between the 2 groups were compared with the t student and chi-square statistics methods.
RESULTS
There were no significant differences in gender, age, the location, length and diameter of the syringomyelia of the 2 groups (P > 0.05). The follow-up period ranged from 6 to 45 months, with a mean of 28.6 months. The average preoperative Cobb angles of coronal main curves of the 2 groups were 71° ± 23° and 68° ± 19°, the postoperative Cobb angles were 27° ± 20° and 25° ± 16°, and the last follow-up Cobb angles were 29° ± 17° and 32° ± 20°. The coronal correction rate was 66% ± 19% in the study group and 65% ± 21% in the control group (t = 0.136, P = 0.893). There was no significant difference at the last follow-up(t = 0.210, P = 0.837). The average preoperative Cobb angles of thoracic kyphosis of the 2 groups were 35° ± 18° and 32° ± 19°, the postoperative Cobb angles were 25° ± 10° and 23° ± 9°, and the last follow-up Cobb angles were 24° ± 4° and 28° ± 8°. The mean sagittal correction rate of the 2 groups were 50% ± 58% and 57% ± 53% (t = -0.303, P = 0.764). There was also no significant difference at the last follow-up time (t = 0.769, P = 0.490). There were no significant difference, in terms of the postoperative of the apical vertebra translation, apical vertebra rotation and trunk shift between the 2 groups (P > 0.05). One case in the study group complicated with a pedicle screw breaking the anterior cortex of the vertebra and one in the control group complicated with a hook loosening, postoperatively. At the last follow-up time, the neurological symptoms of the 2 groups got no aggravating.
CONCLUSION
One-stage posterior correction of scoliosis associated with little symptomatic syringomyelia may be effective and safe. | pubmed_810_10544 |
pubmed_111_19095 | A dichotic listening test was employed to test the hypothesis that behavior disorders might have an abnormal laterality patterns of cerebral function. Eighteen behavior disorder out-patients of the psychiatry department at an university hospital and seventeen normal subjects were requested to recall dichotically presented words. The results showed that compared with the normal controls, the subjects with behavior disorders yielded less prominent right ear advantage, lesser response ear alternations, but better overall performances. The results do not support the hypothesis of the left hemisphere dysfunction in behavior disorders but suggest the possibility of the right hemisphere dysfunction. | 10.3109/00207458509149769 |
pubmed_817_11519 | INTRODUCTION
Bladder cancer assessment with non-invasive gene expression signatures facilitates the detection of patients at risk and surveillance of their status, bypassing the discomforts given by cystoscopy. To achieve accurate cancer estimation, analysis pipelines for gene expression data (GED) may integrate a sequence of several machine learning and bio-statistical techniques to model complex characteristics of pathological patterns.
METHODS
Numerical experiments tested the combination of GED preprocessing by discretization with tree ensemble embeddings and nonlinear dimensionality reductions to categorize oncological patients comprehensively. Modeling aimed to identify tumor stage and distinguish survival outcomes in two situations: complete and partial data embedding. This latter experimental condition simulates the addition of new patients to an existing model for rapid monitoring of disease progression. Machine learning procedures were employed to identify the most relevant genes involved in patient prognosis and test the performance of preprocessed GED compared to untransformed data in predicting patient conditions.
RESULTS
Data embedding paired with dimensionality reduction produced prognostic maps with well-defined clusters of patients, suitable for medical decision support. A second experiment simulated the addition of new patients to an existing model (partial data embedding): Uniform Manifold Approximation and Projection (UMAP) methodology with uniform data discretization led to better outcomes than other analyzed pipelines. Further exploration of parameter space for UMAP and t-distributed stochastic neighbor embedding (t-SNE) underlined the importance of tuning a higher number of parameters for UMAP rather than t-SNE. Moreover, two different machine learning experiments identified a group of genes valuable for partitioning patients (gene relevance analysis) and showed the higher precision obtained by preprocessed data in predicting tumor outcomes for cancer stage and survival rate (six classes prediction).
CONCLUSIONS
The present investigation proposed new analysis pipelines for disease outcome modeling from bladder cancer-related biomarkers. Complete and partial data embedding experiments suggested that pipelines employing UMAP had a more accurate predictive ability, supporting the recent literature trends on this methodology. However, it was also found that several UMAP parameters influence experimental results, therefore deriving a recommendation for researchers to pay attention to this aspect of the UMAP technique. Machine learning procedures further demonstrated the effectiveness of the proposed preprocessing in predicting patients' conditions and determined a sub-group of biomarkers significant for forecasting bladder cancer prognosis. | 10.1186/s13040-022-00306-w |
pubmed_182_7234 | Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000-December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%-91.5%), with high heterogeneity (Q 2 test: P<0.001; I2=83.63%). All studies reported toxicity data. Acute and late toxicity (grade ≥3) rates were 3.3%-18.0% and 6.0%-8.2%, respectively. Reported gastrointestinal side effects were duodenal obstruction/ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation. SBRT achieves pain relief in most patients with pancreatic cancer with an acceptable gastrointestinal toxicity rate. Further prospective studies are needed to define optimal dose/fractionation and the best systemic therapies modality integration to reduce toxicity and improve the palliative outcome. Finally, the quality of life and, particularly, pain control should be considered as an endpoint in all future trials on this emerging treatment technique. | 10.2147/JPR.S167994 |
pubmed_333_8865 | Spontaneous gonadotrophin release and the gonadotrophin response to LH releasing factor (RF) were studied in pro-oestrus, androgenized female and male rats. The animals were either intact or gonadectomized (about 32 h previously) and treated with various steroids. The gonadotrophin response (especially LH) was much lower in intact males and androgenized females than in pro-oestrous females. Oestrogen plus progesterone increased plasma gonadotrophin concentrations and responses in ovariectomized rats, but inhibited the increase in the plasma gonadotrophin concentration and the LH response which followed castration in males. As in the normal female, ovariectomy decreased the LH response but increased the plasma FSH concentration and response in the androgenized female; oestrogen and progesterone had relatively little effect. Apart from reducing the postcastration rise in plasma FSH, testosterone had no significant effect in gonadectomized male or female animals. These results show that the effect of steroids on the gonadotrophin response to LH-RF as well as the spontaneous secretion of gonadotrophin depends upon sexual differentiation of the hypothalamo-hypophysial system. Studies with various metabolites of progesterone indicated that the facilitatory action of this steroid could be due, in part, to a 5alpha-reduced derivative. | 10.1677/joe.0.0730157 |
pubmed_332_14750 | UNLABELLED
Plum pox virus (PPV) is the causal agent of Sharka, considered to be the most detrimental viral disease of Prunus spp. worldwide. So far, several PPV strains have been recognized, three of them (PPV-D, PPV-M, and PPV-Rec) having shown serious economic impact in the European area. Infectious cDNA clones of plant RNA viruses are excellent tools for functional studies of viral genomes. Preparation and use of PPV-D and PPV-M infectious clones have been previously reported. Here we describe the construction of an infectious cDNA clone of the strain PPV-Rec (isolate BOR-3) by the strategy involving the subsequent exchanges of homologous BOR-3 genome parts in the backbone of the previously prepared PPV-D infectious construct. The infectivity of each intermediate chimeric cDNA as well as that of the final construct (pIC-PPV-Rec) was confirmed by biolistic transfection of Nicotiana benthamiana plants. Complete sequence of the cloned viral BOR-3 cDNA revealed 0.14% of difference at the nucleotide level compared to original BOR-3 sequence, resulting in four amino acid changes. This slight inequality was related to the population heterogeneity of the initial BOR-3 isolate; no difference in the amino acid sequence resulted from the cloning steps performed.
KEYWORDS
inter-strain chimera; biolistics; genome sequence. | 10.4149/av_2012_02_129 |
pubmed_597_11950 | The hydride transfer reaction catalyzed by dihydrofolate reductase (DHFR) is a model for examining how protein dynamics contribute to enzymatic function. The relationship between functional motions and enzyme evolution has attracted significant attention. Recent studies on N23PP Escherichia coli DHFR (ecDHFR) mutant, designed to resemble parts of the human enzyme, indicated a reduced single turnover rate. NMR relaxation dispersion experiments with that enzyme showed rigidification of millisecond Met-20 loop motions (Bhabha, G., Lee, J., Ekiert, D. C., Gam, J., Wilson, I. A., Dyson, H. J., Benkovic, S. J., and Wright, P. E. (2011) Science 332, 234-238). A more recent study of this mutant, however, indicated that fast motions along the reaction coordinate are actually more dispersed than for wild-type ecDHFR (WT). Furthermore, a double mutant (N23PP/G51PEKN) that better mimics the human enzyme seems to restore both the single turnover rates and narrow distribution of fast dynamics (Liu, C. T., Hanoian, P., French, T. H., Hammes-Schiffer, S., and Benkovic, S. J. (2013) Proc. Natl. Acad. Sci. U.S.A. 110, 10159-11064). Here, we measured intrinsic kinetic isotope effects for both N23PP and N23PP/G51PEKN double mutant DHFRs over a temperature range. The findings indicate that although the C-H→C transfer and dynamics along the reaction coordinate are impaired in the altered N23PP mutant, both seem to be restored in the N23PP/G51PEKN double mutant. This indicates that the evolution of G51PEKN, although remote from the Met-20 loop, alleviated the loop rigidification that would have been caused by N23PP, enabling WT-like H-tunneling. The correlation between the calculated dynamics, the nature of C-H→C transfer, and a phylogenetic analysis of DHFR sequences are consistent with evolutionary preservation of the protein dynamics to enable H-tunneling from well reorganized active sites. | 10.1074/jbc.M113.507632 |
others_239_11057 | The present study examined whether treatment of in vitro matured pig oocytes with calcium ionophore (A23187) could prevent polyspermic penetration in vitro. When oocytes cultured for maturation for 33, 36 or 44 h were subsequently treated with 50 μM A23187 in medium with fetal calf serum (FCS) for 1, 2 and 3 h and then cultured for 12 h without spermatozoa, virtually no activation occurred. In the absence of FCS, however, 31-42, 45-49 and 56-64% of oocytes were activated, respectively. When oocytes treated with 50 μM A23187 in medium with FCS for 3 h were inseminated in vitro, the penetration rates (14-57%) were lower (p<0.01) with a higher (p<0.01) incidence (35-67%) of monospermy compared with untreated oocytes (69-80% penetration and 15-17% monospermy). However, sperm penetration was completely blocked in all oocytes treated with A23187 in the absence of FCS. When oocytes matured for 33 h were treated with different concentrations of A23187 for 3 h and inseminated in vitro, the penetration rate did not change but there was an increased incidence (p<0.05) of monospermy at 10-20 μM and 2.5-5 μM A23187 in the presence and absence of FCS, respectively, compared with at 0 μM A23187. With these lower concentrations of A23187, treatment of oocytes for at least 60 and 30 min in the presence and absence of FCS, respectively, was required to increase the incidence of monospermy without reducing penetration rate. These results indicate that a high concentration (50 μM) of A23187 in medium without FCS, but not in medium with FCS, stimulated in vitro matured pig oocytes to induce parthenogenetic activation and a complete block to sperm penetration in vitro. However, treatment of oocytes with lower concentrations of A23187 (10-20 μM and 2.5-5 μM) both in the presence and absence of FCS maintained sperm penetration in vitro and increased the incidence of monospermy | 10.5713/ajas.2002.172 |
pubmed_305_17243 | BACKGROUND AND PURPOSE
Percutaneous autologous bone marrow transplantation (PABMT) is a minimally invasive therapeutic strategy for the treatment of delayed bone union in adults, which has been confirmed by many studies. However, there is no report on PABMT application in pediatric orthopedic surgery. The aim of this article was to analyze the therapeutic effect of PABMT in children with delayed union of limb bone and its influence in relation to delayed bone union therapy, transplantation period, patients' sex, fracture location, and fracture fixation.
METHODS
In this study, 53 patients (aged 3-16 years, with an average age of 6.7 years) with delayed union of long bone (20 femurs, 12 tibiae, 10 humeri, 5 radiuses, 5 ulnas, and 1 fibula) were treated using PABMT. Clinical examination and X-ray were integrated to evaluate the therapeutic effect.
RESULTS
All 53 patients were followed up for 2-6 years (average time, 3.5 years). Of the 53 patients, 47 (88.7%) were healed, whereas the other 6 (11.3%) were not, and were subsequently treated by autologous bone grafting. In 30 patients who received their first PABMT treatment 6-8 months after fixation, the clinical cure rate, operation times, and healing time were 83.3%, 5.8±0.5 months, and 2.5±0.6, respectively. In the other 23 patients, whose first PABMT treatments were started within 4 to 6 months after fixation, the clinical cure rate, operation times, and healing time were 95.7% (P=0.167), 3.2±0.3 months (P=0.001), and 1.3±0.6 (P=0.001), respectively. The patients' sex, fracture location, and fracture fixation did not have statistical influence on the clinical efficacy.
CONCLUSION
PABMT is a minimally invasive and effective strategy for the treatment of delayed union of limb bone in children. The early surgical treatment facilitates the fracture healing, reduces the number of transplantation, and shortens the course of treatment. | 10.2147/TCRM.S146426 |
pubmed_506_4656 | BACKGROUND
Intravenous racemic ketamine is commonly administered for procedural sedation, although few pharmacokinetic studies have been conducted among children. Moreover, an optimal sampling schedule has not been derived to enable the conduct of pharmacokinetic studies that minimally inconvenience study participants.
METHODS
Concentration-time data were obtained from 57 children who received 1-1.5 mg·kg(-1) of racemic ketamine as an intravenous bolus. A population pharmacokinetic analysis was conducted using nonlinear mixed effects models, and the results were used as inputs to develop a D-optimal sampling schedule.
RESULTS
The pharmacokinetics of ketamine were described using a two-compartment model. The volume of distribution in the central and peripheral compartments were 20.5 l∙70 kg(-1) and 220 l∙70 kg(-1), respectively. The intercompartmental clearance and total body clearance were 87.3 and 87.9 l·h(-1) ∙70 kg(-1), respectively. Population parameter variability ranged from 34% to 98%. Initially, blood samples were drawn on 3-6 occasions spanning a range of 14-152 min after dosing. Using these data, we determined that four optimal sampling windows occur at 1-5, 5.5-7.5, 10-20, and 90-180 min after dosing. Monte Carlo simulations indicated that these sampling windows produced precise and unbiased ketamine pharmacokinetic parameter estimates.
CONCLUSION
An optimal sampling schedule was developed that allowed assessment of the pharmacokinetic parameters of ketamine among children requiring short-term procedural sedation. | 10.1111/pan.12521 |
pubmed_988_6669 | In experiments on rabbits it has been established that the acute alcoholization causes prolonged uncompensated alterations of such physical and chemical properties of erythrocytes as the average volume, the concentration of dry substance and water, the density, the content of endoerythrocytal hemoglobin, as well as the concentration of erythrocytes and hemoglobin in blood. | pubmed_988_6669 |
pubmed_543_4283 | The present study was undertaken to investigate the effects of neonatal handling on learned helplessness (LH) model of depression in the rat. We also investigated the effect of neonatal handling on behavior in an open field test of emotionality. The handling procedure reduced helplessness behavior, with a decrease in the number of escape failures, an increase in the number of avoidance responses, and a decrease in the escape latency in the shuttle-box after induction of LH. In addition, handling during infancy decreased the number of boli in an open field test, which suggests that the level of emotivity in adulthood was reduced. It is suggested that handling in infancy improves behavioral adaptation to the environment, including enhanced adaptive response to stress. | 10.1016/0031-9384(94)e0113-i |
others_91_17268 | We evaluated a role for protein kinase C (PKC) in the regulation of rabbit tracheal epithelial Na-Cl(K) cotransport. Short-term treatment with phorbol 12-myristate 13-acetate (PMA) dose dependently increased bumetanide- sensitive Na and Cl efflux and elevated staurosporine- and bumetanide- sensitive Na, Cl, and K uptake. PMA and the α(2A)-adrenergic agonist guanabenz both induced cotransport with a stoichiometry of 2 Cl:1 Na and 2 Cl:1 Rb and elevated staurosporine-sensitive PKC activity in cytosolic and particulate fractions. Prolonged PMA treatment did not sustain bumetanide- sensitive 2 Cl:1 Na and 2 Cl:1 Rb transport but did block stimulation of bumetanide-sensitive transport by PMA or guanabenz and elevation of PKC activity by PMA and guanabenz in a particulate fraction. Cells treated with okadaic acid exhibited a staurosporine- and bumetanide-sensitive 2 Cl:1 Na and 2 Cl:1 Rb uptake. In cultured monolayers, basolateral perfusion with epinephrine, isoproterenol, or PMA increased short-circuit current (I(sc)). Basolateral application of bumetanide reduced elevated I(sc) to baseline levels, indicating a role for Cl secretory cells in a reconstituted tracheal epithelium. Pretreatment of transmonolayer cultures with PMA diminished the stimulatory response to epinephrine. These results indicate that, in rabbit tracheal epithelial cells, α-adrenergic stimulation activated Na-2Cl-K cotransport and that PKC is a critical effector in this process | 10.1152/ajpcell.1996.271.1.c338 |
pubmed_745_10183 | This report analyzes the clinical and electrophysiological results of the carpal tunnel release operation in mentally retarded children with mucopolysaccharidoses and discusses the needs for early surgical intervention. | 10.1111/j.1365-2788.1988.tb01391.x |
pubmed_412_8783 | OBJECTIVE
To compare the clinical effect of nebulized budesonide with placebo in acute pediatric asthma.
METHODS
A randomized, controlled, double-blind trial with parallel design was used in the ED of a tertiary care children's hospital. Children aged 6 months to 18 years with a moderate to severe exacerbation of asthma [Pulmonary Index Score (PIS) > or = 5 or < or = 11 after a salbutamol nebulization of 0.15 mg/kg] were eligible. All patients received prednisone 1 mg/kg orally and nebulized salbutamol (0.15 mg/kg) every 30 minutes for 3 doses and then every hour for 4 hours. The intervention was 2 mg (4 mL) of nebulized budesonide or 4 mL of nebulized normal saline.
RESULTS
Baseline characteristics were comparable in the budesonide group (n = 24) and in the placebo group (n = 20). There were no significant differences in the primary outcome measure (PIS) between the 2 groups. However, the PIS at 1 hour had a tendency to be lower in the budesonide group (median = 5) as compared with the placebo group (median = 6; p = 0.07). Survival analysis of release/discharge from the ED/hospital showed a more rapid rate in the budesonide group as compared with the placebo group (p = 0.02). No adverse effects were seen.
CONCLUSION
Although these preliminary results suggest that nebulized budesonide may be an effective adjunct to oral prednisone in the management of moderate to severe asthma exacerbations, a larger trial will be required before the widespread use of inhaled budesonide in acute asthma can be advocated. | 10.1111/j.1553-2712.1998.tb02614.x |
pubmed_171_4050 | PURPOSE
To describe the development of Fuchs' heterochromic iridocyclitis (FHI) following bilateral ocular toxoplasmosis in an Asian Indian female.
METHODS
Case report of a patient with bilateral ocular toxoplasmosis who developed bilateral Fuchs' heterochromic iridocyclitis.
RESULTS
Features characteristic of bilateral Fuchs' heterochromic iridocyclitis developed following several attacks of bilateral toxoplasmic retinochoroiditis in a 26-year-old Indian female patient.
CONCLUSION
Fuchs' heterochromic iridocyclitis can develop over a period of time in patients with ocular toxoplasmosis. | 10.1076/ocii.12.1.75.28065 |
pubmed_963_18167 | OBJECTIVE
To describe the use of second line protease-inhibitor (PI) regimens across Europe and to determine factors associated with virological and immunological response.
DESIGN
Analysis of data from 984 patients with a median follow-up of 21 months enrolled in EuroSIDA. Patients started their second PI-containing regimen at least 16 weeks after starting the first PI-containing regimen and with viral load > 1000 copies/ml.
METHODS
Virological response was defined as a viral load < 500 copies/ml and immunological response as an increase of 50 x 10(6)/l or more in CD4 lymphocyte count.
RESULTS
The median CD4 cell count at starting the second PI was 171 x 10(6) cells/l; viral load was 4.45 log copies/ml. As a second PI regimen, 45% were using a dual PI, while of those on one PI, indinavir (42%) and nelfinavir (34%) were most common. In multivariate Cox models, a higher viral load at starting the second PI [relative hazard (RH), 0.67 per 1 log higher; 95% confidence interval (CI), 0.58-0.77; P < 0.0001) and a lower CD4 cell count (RH, 1.15 per 50% higher; 95% CI, 1.06-1.26; P = 0.0014) were associated with a reduced probability of virological response. Those who had achieved viral suppression on the first PI-regimen were more likely to respond to the second (RH, 1.65; 95% CI, 1.30-2.10; P < 0.0001) as were those who added one or two new nucleosides to their second PI.
CONCLUSIONS
Patients who initiate a second PI regimen at lower viral load, higher CD4 cell count or who added new nucleosides tended to be more likely to achieve a viral load < 500 copies/ml. The roles of cross-resistance and adherence in response to second-line regimens needs further investigation. | 10.1097/00002030-200101260-00009 |
pubmed_417_10183 | The X-PRESS, osmotic shock, chloroform treatment, lysozyme treatment and ultrasonic disruption methods to release five different plasmid-mediated beta-lactamases from Escherichia coli and one chromosomal beta-lactamase from Enterobacter cloacae were compared. The main activities of TEM-1, SHV-1, OXA-1, OXA-2, PSE-4 and chromosomal P99 beta-lactamases were found at the same isoelectric point irrespective of the method used. However, additional satellite bands were found with TEM-1, OXA-1, OXA-2 and PSE-4 beta-lactamases released by the lysozyme method. In addition, beta-lactamase released by osmotic shock treatment was found to be unstable during storage at -20 degrees C or during the 18 h period of iso-electric focusing at +4 degrees C. Chloroform treatment produced similar band patterns and at least as good an enzyme yield as ultrasonic disintegration and was equally simple and fast to perform. | 10.1093/jac/32.6.809 |
pubmed_617_18159 | OBJECTIVES
To determine which staff behaviours and interventions were helpful to a family who had a child die in the intensive care unit (ICU) and which behaviours could be improved.
METHODS
Families whose child died six to 18 months earlier were invited to participate. Families whose child's death involved a coroner's inquiry were excluded. Family members were interviewed by a grief counselor, and completed the Grief Experience Inventory Profile and an empirically designed questionnaire.
RESULTS
No family refused to participate. All family members (13 families, 24 individuals) reported that they wanted, were offered and had: time to be alone with their child, time to hold the child, chances to discuss their feelings, and an opportunity to cry and express their emotions openly. Tangible mementos of the child were appreciated. Support provided by nursing staff was rated as excellent. Some physicians appeared to be abrupt, cold and unfeeling. Hospital social workers and chaplains, when available, were appreciated. Parents valued access to private space and holding their child, but these options needed to be suggested, as they did not know to ask for them. Some families wanted more information about funeral arrangements; most wanted more timely information about autopsy results and feedback on organ donations. Follow-up contact from the hospital about four weeks after the death was valued. Families saw the study as an opportunity to provide feedback that may help others.
CONCLUSIONS
Many acute bereavement interventions need to be initiated by staff because families do not know to request them. Physicians do not always meet individual family's needs for support. Contact initiated by staff following a death is appreciated. | 10.1093/pch/8.6.357 |
pubmed_576_5184 | Glucocorticoids (GCs), important regulators of epidermal growth, differentiation, and homeostasis, are used extensively in the treatment of skin diseases. Using keratin gene expression as a paradigm of epidermal physiology and pathology, we have developed a model system to study the molecular mechanism of GCs action in skin. Here we describe a novel mechanism of suppression of transcription by the glucocorticoid receptor (GR) that represents an example of customizing a device for transcriptional regulation to target a specific group of genes within the target tissue, in our case, epidermis. We have shown that GCs repress the expression of the basal-cell-specific keratins K5 and K14 and disease-associated keratins K6, K16, and K17 but not the differentiation-specific keratins K3 and K10 or the simple epithelium-specific keratins K8, K18, and K19. We have identified the negative recognition elements (nGREs) in all five regulated keratin gene promoters. Detailed footprinting revealed that the function of nGREs is to instruct the GR to bind as four monomers. Furthermore, using cotransfection and antisense technology we have found that, unlike SRC-1 and GRIP-1, which are not involved in the GR complex that suppresses keratin genes, histone acetyltransferase and CBP are. In addition, we have found that GR, independently from GREs, blocks the induction of keratin gene expression by AP1. We conclude that GR suppresses keratin gene expression through two independent mechanisms: directly, through interactions of keratin nGREs with four GR monomers, as well as indirectly, by blocking the AP1 induction of keratin gene expression. | 10.1128/MCB.20.12.4328-4339.2000 |
pubmed_615_22658 | Exposure and sensitivity to ubiquitous airborne fungi such as Alternaria alternata have long been implicated in the development, onset, and exacerbation of chronic allergic airway disorders. This present study is the first to investigate global changes in host gene expression during the interaction of cultured human bronchial epithelial cells and live Alternaria spores. In in vitro experiments human bronchial epithelial cells (BEAS-2B) were exposed to spores or media alone for 24 h. RNA was collected from three biological replicates per treatment and was used to assess changes in gene expression patterns using Affymetrix Human Genome U133 Plus 2.0 Arrays. In cells treated with Alternaria spores compared to controls, 613 probe sets representing 460 individual genes were found differentially expressed (p ≤ 0.05). In this set of 460 statistically significant, differentially expressed genes, 397 genes were found to be up-regulated and 63 were down-regulated. Of these 397 up-regulated genes, 156 genes were found to be up-regulated ≥2 fold. Interestingly, none of the 63 down-regulated genes were found differentially expressed at ≤-2 fold. Differentially expressed genes were identified following statistical analysis and subsequently used for pathway and network evaluation. Interestingly, many cytokine and chemokine immune response genes were up-regulated with a particular emphasis on interferon-inducible genes. Genes involved in cell death, retinoic acid signaling, and TLR3 response pathways were also significantly up-regulated. Many of the differentially up-regulated genes have been shown in other systems to be associated with innate immunity, inflammation and/or allergic airway diseases. This study now provides substantial information for further investigating specific genes and innate immune system pathways activated by Alternaria in the context of allergic airway diseases. | 10.3389/fmicb.2013.00196 |
pubmed_405_15837 | The structures of ternary systems with water, nonane, and an ionic liquid, with the ionic liquid placed between water and nonane, have been studied using atomistic molecular dynamics simulations. Three different ionic liquids with 1-n-butyl-3-methylimidazolium cation and bromide, tetrafluoroborate, and trifluoromethanesulfonate anions have been studied. The ionic liquids disperse into the aqueous phase quickly and are solubilized in water within 15 ns to form two equivalent nonane-aqueous ionic liquid interfaces. The interfacial region is enriched with ionic liquids due to the amphiphilicity of the cations. The presence of ionic liquids at the interface reduces the interfacial tension between the nonane and water, thus facilitating the mixing of aqueous and nonane phases. The reduction in the interfacial tension is found to be inversely related to the solubility of the corresponding ionic liquid in water. The butyl chains of the cations and the trifluoromethanesulfonate anions present in the interfacial region are found to be preferentially oriented parallel to the interface normal. | 10.1021/jp508950k |
pubmed_899_24187 | We obtained a novel glucose de-repressed mutant of Trichoderma reesei using disparity mutagenesis. A plasmid containing DNA polymerase δ lacking proofreading activity, and AMAI, an autonomously replicating sequence was introduced into T. reesei ATCC66589. The rate of mutation evaluated with 5-fluoroorotic acid resistance was approximately 30-fold higher than that obtained by UV irradiation. The transformants harboring incompetent DNA polymerase δ were then selected on 2-deoxyglucose agar plates with hygromycin B. The pNP-lactoside hydrolyzing activities of mutants were 2 to 5-fold higher than the parent in liquid medium containing glucose. Notably, the amino acid sequence of cre1, a key gene involved in glucose repression, was identical in the mutant and parent strains, and further, the cre1 expression levels was not abolished in the mutant. Taken together, these results demonstrate that the strains of T. reesei generated by disparity mutagenesis are glucose de-repressed variants that contain mutations in yet-unidentified factors other than cre1. | 10.1080/09168451.2015.1104236 |
pubmed_259_19631 | Since 1980 when Sibley and coworkers first described a nodal neoplasm of unknown histogenesis with striking surface microvilli for which they introduced the term "anemone cell," a series of reports have appeared in the literature illustrating tumors with similar ultrastructural features. While most reported cases showed differentiation along a particular line, rare cases remained histogenetically unclear. In this report a case is described of epithelioid gastric gastrointestinal stromal tumor metastatic to the liver, showing conspicuous long microvillus-type cell processes partially or circumferentially coating the cell surfaces, thus qualifying as yet another tumor type with anemone cell features. | 10.1080/01913120309931 |
pubmed_333_1593 | Persistent refractory alopecia areata in 26 patients was treated topically with dinitrochlorobenzene (DNCB). Sixteen patients have had excellent regrowth of hair; three patients could either not be initially sensitized or an adequate allergic contact dermatitis on the scalp did not develop. Two patients discontinued therapy within two months; hair growth did not develop in five patients despite an adequate trial. Augmentation of the T-lymphocyte pool via DNCB sensitization and challenge may become effective therapy for some patients with severe alopecia areata. | pubmed_333_1593 |
pubmed_263_15226 | NAC transcription factors are plant-specific and play important roles in many processes including plant development, response to biotic and abiotic stresses and hormone signaling. So far, only a few NAC genes have been identified to mediate cell death. In this study, we identified a novel NAC gene from canola (Brassica napus L.), BnaNAC103 which induces reactive oxygen species (ROS) accumulation and cell death in Nicotianabenthamiana leaves. We found that BnaNAC103 responded to multiple signalings, including cold, salicylic acid (SA) and a fungal pathogen Sclerotinia sclerotiorum. BnaNAC103 is located in the nucleus. Expression of full-length BnaNAC103, but not either the N-terminal NAC domain or C-terminal regulatory domain, was identified to induce hypersensitive response (HR)-like cell death when expressed in N. benthamiana. The cell death triggered by BnaNAC103 is preceded by accumulation of ROS, with diaminobenzidine (DAB) staining supporting this. Moreover, quantification of ion leakage and malondialdehyde (MDA) of leaf discs indicates significant cell membrane breakage and lipid peroxidation induced by BnaNAC103 expression. Taken together, our work has identified a novel NAC transcription factor gene modulating ROS level and cell death in plants. | pubmed_263_15226 |
pubmed_943_22036 | Cytochromes P450 (P450s) are involved in the oxidative metabolism of a plethora of structurally unrelated compounds, including therapeutic drugs. Two orphan members of the nuclear receptor superfamily, the pregnane X receptor (PXR; NR1I2) and constitutive androstane receptor (CAR; NR1I3) have been implicated in this phenomenon. In the present study, we examined the transcriptional regulation of the human CYP2B6 gene. In primary cultures of human hepatocytes, CYP2B6 was highly inducible by a number of compounds known to be human PXR ligands, including rifampicin and hyperforin. PXR was shown to be capable of activating the phenobarbital-responsive enhancer module (PBREM) region of the CYP2B6 gene, a 51-base-pair enhancer element that mediates induction of CYP2B6 expression by CAR. The two nuclear receptor-binding motifs within the PBREM effectively bound PXR as a heterodimer with the 9-cis retinoic acid receptor alpha (NR2B1). Taken together, these observations demonstrate that the CYP2B6 gene is directly regulated by PXR and further establish this receptor as a key regulator of drug-metabolizing P450s. | pubmed_943_22036 |
pubmed_28_18960 | Stainless steel, widely present in the food industry, is frequently exposed to bacterial colonization with possible consequences on consumers' health. 288 stainless steel disks with different roughness (0.25, 0.5 and 1 μm) were challenged with four Gram-negative (Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 1402, Yersinia enterocolitica ATCC 9610 and Pseudomonas aeruginosa ATCC 27588) and four Gram-positive bacteria (Staphylococcus aureus ATCC 6538, Enterococcus faecalis ATCC 29212, Bacillus cereus ATCC 14579 and Listeria monocytogenes NCTT 10888) and underwent three different sanitizing treatments (UVC, alcohol 70% v/v and Gold lotion). Moreover, the same procedure was carried out onto the same surfaces after a nanotechnological surface coating (nanoXHAM® D). A significant bactericidal effect was exerted by all of the sanitizing treatments against all bacterial strains regardless of roughness and surface coating. The nanoXHAM® D coating itself induced an overall bactericidal effect as well as in synergy with all sanitizing treatments regardless of roughness. Stainless steel surface roughness is poorly correlated with bacterial adhesion and only sanitizing treatments can exert significant bactericidal effects. Most of sanitizing treatments are toxic and corrosive causing the onset of crevices that are able to facilitate bacterial nesting and growth. This nanotechnological coating can reduce surface adhesion with consequent reduction of bacterial adhesion, nesting, and growth. | 10.3390/microorganisms9020248 |
pubmed_737_14217 | Laboratory observations of electromagnetic ion-cyclotron waves generated by a localized transverse dc electric field are reported. Experiments indicate that these waves result from a strong E×B flow inhomogeneity in a mildly collisional plasma with subcritical magnetic field-aligned current. The wave amplitude scales with the magnitude of the applied radial dc electric field. The electromagnetic signatures become stronger with increasing plasma β, and the radial extent of the power is larger than that of the electrostatic counterpart. Near-Earth space weather implications of the results are discussed. | 10.1103/PhysRevLett.106.185001 |
pubmed_112_795 | Alternate explanations of loneliness proposed by Weiss (1973)--the situational theory and the characterological theory--were tested in samples of early (N = 113), middle (N = 106), and late (N = 106) adolescents. In addition to completing the Revised UCLA Loneliness Scale, participants completed instruments linked to either the situational or characterological explanation of loneliness. Data were analyzed using hierarchical analysis of sets. For early adolescents, the results indicated that the characterological set of variables explained somewhat more variance in loneliness than did the situational set of variables. These findings did not replicate those of the original study (Mahon & Yarcheski, 1988). For middle and late adolescents, the results indicated that the situational set of variables explained more variance in loneliness than did the characterological set. | pubmed_112_795 |
pubmed_720_20307 | PURPOSE
This study is the first description of hospital-wide anti-infective use according to clinical indication for a pediatric hospital. Children's Hospital Colorado (CHCO) is uniquely poised to examine its anti-infective use after the implementation of provider-selected order indications (PSOIs), which are distinct from Diagnosis Related Group classifications in that they are used for clinical treatment as opposed to final diagnosis codes for billing and thus are more granular.
METHODS
This study used our institution's mandatory PSOIs to describe overall clinical indications for anti-infective use. For 2016, all anti-infective orders were extracted from the electronic medical record (Epic), including drug name, route, prescribing unit, and PSOI. We calculated the number of times each drug was associated with each indication and the number of times an indication was attributed to each drug, and then analyzed these data in Excel.
FINDINGS
There were 29,258 orders at CHCO in 2016 with at least 1 indication. The most common clinical indication was "prophylaxis-medical/surgical," accounting for 23% of all orders and commonly associated with cefazolin (42% of prophylaxis-medical/surgical orders). This was followed by the indications of "sepsis/bacteremia" and "pneumonia/sinusitis." The most commonly prescribed anti-infectives for nonprophylactic clinical indications were IV vancomycin (14%), ceftriaxone (11%), and ampicillin (6%).
IMPLICATIONS
Knowledge of the clinical reasons for hospital-wide anti-infective use enables hospitals to identify targets for improved use through education and guideline and policy development. This description provides better details than billing codes about the clinical reasons anti-infectives are used and offers a useful template for implementation at other hospitals. | 10.1016/j.clinthera.2019.05.008 |
pubmed_238_21011 | OBJECTIVES
Few case reports have demonstrated promising results of drug-coated balloons (DCBs) as an emerging management for carotid artery in-stent restenosis (CAISR). Herein, we report 6 cases of CAISR which were treated with a DCB with or without new stent deployment.
BACKGROUND
Carotid artery in-stent restenosis is a high-risk condition with an estimated incidence rate that varies widely from 6% to 40%. Several strategies are available now for the management of the CAISR including conventional balloon angioplasty, plaque modification balloon angioplasty, and new stent placement.
METHODS
A retrospective review of consecutive patients with a diagnosis of severe CAISR at Baylor Scott & White The Heart Hospital Plano from 2011 to 2021 was performed. This study was approved by the Baylor Scott & White Research Institute institutional review board.
RESULTS
Six patients underwent DCB angioplasty with or without stent placement under an embolic protection device. Resolution of CAISR was achieved in all cases with 0% to 10% residual stenosis in all cases. Following the procedure, 1 patient had a brief episode of syncope with balloon inflation with immediate recovery on deflation of the balloon. There were otherwise no significant neurological or cardiac events prior to discharge. All patients were asymptomatic at their follow-up visit with no neurological or cardiac events reported at 12, 24, and 36 months following the procedure.
CONCLUSION
While CAISR treatment remains a challenging condition, our study shows that the use of DCB with or without stent placement is a feasible and promising treatment option when compared with other conventional treatment options.
CLINICAL IMPACT
Carotid artery in-stent restenosis treatment remains a challenging condition. Our study shows that the use of drug coated balloon with or without stent placement is a feasible and promising treatment option when compared with current conventional treatment options. | 10.1177/15266028221120763 |
pubmed_22_3779 | The millipede genus Trichopeltis Pocock, 1894 contains 12 described species including a new species from southern China described here. Trichopeltis sutcharitisp. n. can be distinguished from congeners by its gonopods that are strongly caudolaterally curved and have a prominent, high, curved, densely setose process on each coxa. An updated checklist and a distribution map are provided for all species of the genus. | 10.3897/zookeys.725.22014 |
pubmed_799_16573 | The objective of this study was to quantify and assess for the first time the variability of total mercury in urban soils at a European level, using a systematic sampling strategy and a common methodology. We report results from a comparison between soil samples from Aveiro (Portugal), Glasgow (Scotland), Ljubljana (Slovenia), Sevilla (Spain), Torino (Italy) and Uppsala (Sweden). At least 25 sampling points (in about 4-5 ha) from a park in each city were sampled at two depths (0-10 and 10-20 cm). Total mercury was determined by pyrolysis atomic absorption spectrometry with gold amalgamation. The quality of results was monitored using certified reference materials (BCR 142R and BCR 141R). Measured total mercury contents varied from 0.015 to 6.3 mg kg(-1). The lowest median values were found in Aveiro, for both surface (0-10 cm) and sub-surface (10-20 cm) samples (0.055 and 0.054 mg kg(-1), respectively). The highest median mercury contents in soil samples were found in samples from Glasgow (1.2 and 1.3 mg kg(-1), for surface and sub-surface samples, respectively). High variability of mercury concentrations was observed, both within each park and between cities. This variability reflecting contributions from natural background, previous anthropogenic activities and differences in the ages of cities and land use, local environmental conditions as well as the influence of their location within the urban area. Short-range variability of mercury concentrations was found to be up to an order of magnitude over the distance of only a few 10 m. | 10.1016/j.scitotenv.2006.04.008 |
pubmed_249_12334 | We applied a differential display PCR technique to isolate molecules that are area-specific in expression in the primate neocortex, and found that growth/differentiation factor 7 (GDF7), a member of the bone morphogenetic protein (BMP)/transforming growth factor (TGF) beta super-family, is preferentially expressed in the primary motor area of African green monkeys (Cercopithecus aethiops). We proved that GDF7 is 10 times more abundant in the motor cortex than in the visual cortex by northern blotting and quantitative RT-PCR. When we examined the neocortex of closely related rhesus monkeys (Macaca mulatta), GDF7 was also most abundant in the motor cortex, although the regional difference was reduced to 3-fold. This differential expression pattern was observed in both newborn and infant rhesus monkeys. We found that several type I/II receptors of BMP, candidates of the receptors for GDF7, are uniformly expressed in the mature neocortex. The unique expression pattern of GDF7 suggests that it may play an active role in the motor area of the primate neocortex. | 10.1046/j.1471-4159.2001.00177.x |
others_161_3106 | Methanolic extract of root parts of Achyranthes aspera L. (Amaranthaceae) as tested for its effect on aflotoxicosis rats at five dose levels. Aflotoxin intoxication in rats significantly (p < 0.001) elevated the levels of SGPT, SGOT, ALKP, and total bilirubin, which indicated acute hepatocellular, damage and biliary obstruction. Methanol extract showed dose dependent decrease in the levels of SGPT, SGOT, ALKP and total bilirubin. Minimum effective dose of extract was found to be 100 mg/kg body weight. Results obtained from histopathological studies also supported hepatoprotective activity against aflotoxin induced hepatotoxicity. Thus the study demonstrates that A. aspera possess anti-hepatotoxic effect against aflotoxin. © Global Science Publications | others_161_3106 |
pubmed_6_19877 | Exposure to the stressful environment results in excessive generation of reactive oxygen species (ROS) or reactive nitrogen species (RNS) in anaerobes, which causes deterioration of microbial activities in biological wastewater treatment systems. Although the genes involved in oxidative stress defense have been primarily identified in the genome of Candidatus Kuenenia stuttgartiensis (a typical anammox species), their function is still not verified. Therefore, the expression of putative antioxidation genes kat, sor, and sod in anammox bacteria was studied by in situ transcription and function validated by heterologous expression under the typical ROS (H2O2) and RNS (NO) stress. After H2O2 and NO additions, the genes involved in the anammox central metabolism (nirS, hzsB, and hdh) were immediately down expressed consistent with the decreased anammox activity. However, the expression of putative antioxidation gene kat did not rise when exposed to H2O2; whereas, its encoding protein KAT enhanced the antioxidant actively of anammox bacteria by H2O2 decomposition like the oxidoreductase enzyme catalase. The sod and sor gene were upregulated with NO treatment, and SOD and SOR can combine with NO and decrease its concentration efficiently. These confirmed the important role of kat, sod, and sor as ROS/RNS scavengers in anammox bacteria, with which anammox bacteria protect themselves when they are exposed to the stressful environment. These verified functional enzymes provide directions for the future regulation of anammox systems, which helps to mitigate the inhibitory effect of the stressful environment on anammox bacteria. | 10.1016/j.chemosphere.2021.131008 |
pubmed_1033_1240 | Cytomegalovirus (CMV) serological status of transplant donors and recipients has important implications on antiviral prophylaxis, morbidity/mortality, donor selection and hospital stay. We evaluated CMV prevalence in our islet transplant candidates (ITC) in comparison with organ donors. We correlated the CMV serological status of our ITC with serology for Epstein-Barr virus and Parvovirus B19, auto-antibodies, patient's age, age at DM onset, duration of DM, gender, race, ABO group, HLA haplotype and C-peptide levels. Cytomegalovirus transmission after islet transplant using the Edmonton regimen was also evaluated. Cytomegalovirus seropositivity varied according to patient group, age, gender and race. Type 1 DM patients had reduced odds of CMV seropositivity when compared with organ donors. In all groups studied, older patients, females, and non-Caucasians were more likely to be CMV seropositive. In addition, no CMV reactivation, infection or disease was observed among our transplanted patients using this steroid-free regimen even after donor/recipient CMV mismatch. | 10.1111/j.1600-6143.2004.00557.x |
pubmed_851_1028 | Increased use of biofuels raises concerns about health effects of new emissions. We analyzed relative lung health effects, on Fisher 344 rats, of diesel engine exhausts emissions (DEE) from a Euro 5-classified diesel engine running on petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without diesel particulate filter (DPF). One group of animals was exposed to DEE for 7 days (6 h/day), and another group for 28 days (6 h/day, 5 days/week), both with and without DPF. The animals (n = 7/treatment) were exposed in whole body exposure chambers. Animals breathing clean air were used as controls. Genotoxic effects of the lungs by the Comet assay, histological examination of lung tissue, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury, and mRNA markers of inflammation and oxidative stress were analyzed. Our results showed that a minor number of genes related to inflammation were slightly differently expressed in the exposed animals compared to control. Histological analysis also revealed only minor effects on inflammatory tissue markers in the lungs, and this was supported by flow cytometry and ELISA analysis of cytokines in BALF. No exposure-related indications of genotoxicity were observed. Overall, exposure to DEE with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF. Overall, exposure to DEE from a modern Euro 5 light vehicle engine run on B20 fuel with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF. | 10.1080/08958378.2017.1339149 |
pubmed_744_21685 | INTRODUCTION
We investigated the status of erectile function and urinary continence after radical prostatectomy to investigate a possible relation between them and then determined whether the status of postoperative urinary continence affected erectile function.
PATIENTS AND METHODS
Seventy-six patients who had no symptoms of erectile dysfunction or urinary incontinence preoperatively were included in this study. The postoperative status of erectile function and urinary continence was investigated using a self-reported patient questionnaire.
RESULTS
Thirteen of 27 patients (48.1%) who underwent nerve-sparing procedures maintained erectile function, while 7 of 49 patients (14.2%) who underwent non-nerve-sparing procedures maintained it postoperatively. None of the 27 patients in the nerve-sparing procedure group reported incontinence, whereas 3 of the 49 patients (6.1%) who underwent non-nerve-sparing procedures reported moderate incontinence. However, no significant correlation between the International Index of Erectile Function-5 score and the Incontinence Impact Questionnaire score was seen.
CONCLUSION
No relation between the status of urinary continence and erectile function was shown, regardless of the nerve-sparing nature of the prostatectomy. | 10.1159/000078801 |
pubmed_434_6981 | Small-molecule target identification is a vital and daunting task for the chemical biology community as well as for researchers interested in applying the power of chemical genetics to impact biology and medicine. To overcome this "target ID" bottleneck, new technologies are being developed that analyze protein-drug interactions, such as drug affinity responsive target stability (DARTS), which aims to discover the direct binding targets (and off targets) of small molecules on a proteome scale without requiring chemical modification of the compound. Here, we review the DARTS method, discuss why it works, and provide new perspectives for future development in this area. | 10.1021/cb100294v |
pubmed_769_19577 | BACKGROUND
Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. High-throughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes.
METHOD
We applied exome sequencing to identify potential variants causing syndromic intellectual disability in six Sudanese patients from four unrelated families. Data sharing through the Varsome portal corroborated the diagnosis of one of these patients and a Tunisian patient investigated through exome sequencing. Sanger sequencing validated the identified variants and their segregation with the phenotypes in the five studied families.
RESULT
We identified three pathogenic/likely pathogenic variants in CCDC82, ADAT3, and HUWE1 and variants of uncertain significance in HERC2 and ATP2B3. The patients with the CCDC82 variants had microcephaly and spasticity, two signs absent in the two previously reported families with CCDC82-related intellectual disability.
CONCLUSION
In conclusion, we report new patients with pathogenic mutations in the genes CCDC82, ADAT3, and HUWE1. We also highlight the possibility of extending the CCDC82-linked phenotype to include spastic paraplegia and microcephaly. | 10.1111/ahg.12460 |
pubmed_80_16680 | INTRODUCTION
Big-data-driven drug development resources and methodologies have been evolving with ever-expanding data from large-scale biological experiments, clinical trials, and medical records from participants in data collection initiatives. The enrichment of biological- and clinical-context-specific large-scale data has enabled computational inference more relevant to real-world biomedical research, particularly identification of therapeutic targets and drugs for specific diseases and clinical scenarios.
AREAS COVERED
Here we overview recent progresses made in the fields: new big-data-driven approach to therapeutic target discovery, candidate drug prioritization, inference of clinical toxicity, and machine-learning methods in drug discovery.
EXPERT OPINION
In the near future, much larger volumes and complex datasets for precision medicine will be generated, e.g., individual and longitudinal multi-omic, and direct-to-consumer datasets. Closer collaborations between experts with different backgrounds would also be required to better translate analytic results into prognosis and treatment in the clinical practice. Meanwhile, cloud computing with protected patient privacy would become more routine analytic practice to fill the gaps within data integration along with the advent of big-data. To conclude, integration of multitudes of data generated for each individual along with techniques tailored for big-data analytics may eventually enable us to achieve precision medicine. | 10.1080/23808993.2019.1617632 |
pubmed_1049_534 | OBJECTIVE
To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications.
METHODS
A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status.
RESULTS
For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%).
CONCLUSION
Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted. | 10.1002/(SICI)1098-0997(1998)6:6<237::AID-IDOG3>3.0.CO;2-E |
pubmed_341_18849 | INTRODUCTION
Visualization of the retroplacental clear space (RPCS) may provide critical insight into the development of abnormally invasive placenta (AIP). In this pre-clinical study, we characterized the appearance of the RPCS on magnetic resonance imaging (MRI) during the second half of gestation using a liposomal gadolinium contrast agent (liposomal-Gd).
MATERIALS AND METHODS
Studies were performed in fifteen pregnant C57BL/6 mice at 10, 12, 14, 16, and 18 days of gestation. MRI was performed on a 1T permanent magnet scanner. Pre-contrast and post-contrast images were acquired using T1-weighted gradient-recalled echo (T1w-GRE) and T2-weighted fast spin echo (T2w-FSE) sequences. Animals were euthanized after imaging and feto-placental units harvested for histological examination. Visualization of the RPCS was scored by a maternal-fetal radiologist and quantified by measuring the contrast-to-noise ratio (CNR) on T1w images. Feto-placental features were segmented for analysis of volumetric changes during gestation.
RESULTS
Contrast-enhanced T1w images enabled the visualization of structural changes in placental development between days 10-18 of gestation. Although the placental margin on the fetal side was clearly visible at all time points, the RPCS was partially visible at day 10 of gestation, and clearly visible by day 12. Hematoxylin and eosin (H&E) staining of the placental tissue corroborated MRI findings of structural and morphological changes in the placenta.
CONCLUSIONS
Contrast-enhanced MR imaging using liposomal-Gd enabled adequate visualization of the retroplacental clear space starting at day 12 of gestation. The agent also enabled characterization of placental structure and morphological changes through gestation. | 10.1016/j.placenta.2019.01.017 |
pubmed_75_5576 | Subcutaneous insertion of a wire bow functioning as an antenna around the cartilage of the outer ear canal keeps the signal transmission free from artefacts for the electrical stimulation of a deaf ear. With this method it is not necessary to drill a bony inlet in the area of the temporal bone by inserting the cochlear implant in the fossa infratemporalis. The energy transmission is facilitated, and energy transfer to the cochlear implant is reduced. The ceramic implant is not visible. The patient is able to swim and can switch on the speech processor if required, similar to a hearing aid. | pubmed_75_5576 |
pubmed_1057_23102 | Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disorder. Here, we performed a bioinformatics analysis using the GSE102660 dataset from the Gene Expression Omnibus database to identify differentially expressed circRNAs (DEcircRNAs) in tissues from IPF patients and healthy controls. The results identified 45 DEcircRNAs, among which expression of hsa_circ_0044226 was markedly higher in lung tissues from IPF patients than from healthy controls. Knocking down hsa_circ_0044226 expression using a targeted shRNA inhibited TGF-β1-induced fibrosis in RLE-6TN cells and in a bleomycin-induced mouse model of IPA. The diminished TGF-β1-induced fibrosis was associated with upregulated expression of E-cadherin and downregulated expression of α-SMA, collagen III and fibronectin 1, as well as with reduced expression of CDC27, suggesting inhibition of epithelial-to-mesenchymal transition (EMT). All of those effects were reversed by overexpression of CDC27. This suggests CDC27 overexpression abolishes the antifibrotic effect of hsa_circ_0044226 knockdown through activation of EMT. Furthermore, hsa_circ_0044226 knockdown decreased the expression of CDC27 in BLM-induced pulmonary fibrosis mouse model. Collectively then, these findings indicate that downregulation of hsa_circ_0044226 attenuates pulmonary fibrosis in vitro and in vivo by inhibiting CDC27, which in turn suppresses EMT. This suggests hsa_circ_0044226 may be a useful therapeutic target for the treatment of IPF. | 10.18632/aging.103543 |
pubmed_448_2559 | Species interactions shape the evolution of traits, life histories and the pattern of speciation. What is less clear is whether certain types of species interaction are more or less likely to lead to phenotypic divergence among species. We used the brood pollination mutualism between yuccas and yucca moths to test how mutualistic (pollination) and antagonistic (oviposition) traits differ in the propensity to increase phenotypic divergence among pollinator moths. We measured traits of the tentacular mouthparts, structures used by females to actively pollinate flowers, as well as ovipositor traits to examine differences in the rate of evolution of these two suites of traits among pollinator species. Morphological analyses revealed two distinct groups of moths based on ovipositor morphology, but no such groupings were identified for tentacle morphology, even for moths that pollinated distantly related yuccas. In addition, ovipositor traits evolved at significantly faster rates than tentacular traits. These results support theoretical work suggesting that antagonism is more likely than mutualism to lead to phenotypic divergence. | 10.1111/jeb.13967 |
pubmed_98_20769 | PURPOSE
To study the correlation between choroidal thickness (CT) and IOP control in primary angle-closure glaucoma (PACG).
METHODS
In total, 61 patients (102 eyes) with PACG underwent subfoveal CT (SFCT) scanning using enhanced depth imaging-optical coherence tomography. The subjects with PACG were further grouped as controlled IOP (≤21 mm Hg on maximal medical therapy) and uncontrolled IOP (>21 mm Hg on maximal medical therapy). The average CT of the PACG eyes was calculated and compared between both groups. A correlation analysis was done between CT and intereye difference in CT with the disease parameters.
RESULTS
The mean CT was 274.38 ± 42.10 μm in 102 PACG eyes. SFCT was significantly increased in the uncontrolled IOP group as compared with the controlled IOP group. The mean SFCT was 245.57 ± 62.10 μm in the controlled group and 294.46 ± 51.05 μm in the uncontrolled group (P < 0.01). Factors associated with a thicker choroid were younger age, high IOP, and higher optic nerve head cupping (P < 0.001). Neither the visual field-mean deviation (VF-MD) nor pattern standard deviation (PSD) was found to be associated with overall CT. The intereye asymmetry between CT was significantly associated with poor VF-MD and PSD.
CONCLUSION
PACG eyes with thicker choroid may be a risk factor for poor IOP control on medical anti-glaucoma therapy. Thicker choroid as compared to the fellow eye is a poor prognostic sign and these eyes should be monitored closely. | 10.4103/ijo.IJO_824_21 |
pubmed_125_12774 | OBJECTIVE
To compare the detection rate of clinically significant cancer (CSCa) by magnetic resonance imaging-targeted biopsy (MRI-TB) with that by standard systematic biopsy (SB) and to evaluate the role of MRI-TB as a replacement from SB in men at clinical risk of prostate cancer.
METHODS
The non-systematic literature was searched for peer-reviewed English-language articles using PubMed, including the prospective paired studies, where the index test was MRI-TB and the comparator text was SB. Also the randomized clinical trials (RCTs) are included if one arm was MRI-TB and another arm was SB.
RESULTS
Eighteen prospective studies used both MRI-TB and TRUS-SB, and eight RCT received one of the tests for prostate cancer detection. In most prospective trials to compare MRI-TB vs. SB, there was no significant difference in any cancer detection rate; however, MRI-TB detected more men with CSCa and fewer men with CISCa than SB.
CONCLUSION
MRI-TB is superior to SB in detection of CSCa. Since some significant cancer was detected by SB only, a combination of SB with the TB technique would avoid the underdiagnosis of CSCa. | 10.1007/s00345-020-03366-x |
pubmed_761_24375 | The heterogeneity of prostate cancer has made imaging modalities of crucial importance in this disease. Accurate diagnosis and staging of the volume and extent of disease, especially in advanced and metastatic prostate cancer, can help to tailor the timing and modalities of treatment. While MRI has been effective in the detection of significant prostate cancer, its use in the identification and quantification of extraprostatic disease is limited. This gap is now being filled by PSMA PET. PSMA PET scans have now been shown to have a role in all stages in the prostate cancer journey. Emerging evidence has shown its promise in primary staging, restaging and theranostics. In this paper, we review the evidence for the use of PSMA PET in the various stages of prostate cancer, from initial diagnosis to advanced metastatic disease where other systemic treatments have failed. | 10.1007/s00345-018-2524-z |
pubmed_477_8353 | Erythrocyte membranes obtained from patients with severe megaloblastic anemia contain spectrin as indicated by double immunodiffusion against anti-spectrin raised in rabbits. These membranes have normal protein patterns determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate after solubilization at 100 degrees C for 3 min in SDS. When incubation is carried out at 37 degrees C for 3 hours, however, the membrane protein patterns become grossly abnormal, lacking spectrin, band 3 and having several diffuse smaller bands. Cross-linking of these membranes with SH oxidizing agents, such as diamide prevented this dissociation phenomenon. The SH group content of megaloblastic membranes, both from severe and mild megaloblastic anemia, was significantly higher than that of control membranes. This was also confirmed by the greater incorporation of 3H-N-ethylmalemide into red cell membranes from mild and severe megaloblastic anemia than controls. Incorporation of this probe was greatest into the band 3 region. These findings indicate that the erythrocyte membrane proteins in megaloblastic anemia have an intrinsic abnormality which renders them more susceptible to degradation by their endogenous proteases. | pubmed_477_8353 |
pubmed_752_9990 | A set of mesoporous delaminated montmorillonites containing iron(III)-titanium oxide species was synthesized using two minerals: a bentonite as support and an ilmenite as source of Fe-TiO2 species. Several values of both sulphuric acid concentration and temperature were employed to extract Fe-TiO2 species from an ilmenite. Analyses by X-ray fluorescence, X-ray diffraction, scanning electron microscopy and nitrogen adsorption-desorption confirmed the successful formation of delaminated (or exfoliated) mesoporous structures. Optical properties of solids were determined by UV-Vis diffuse reflectance spectroscopy, and their band gap energy values were also calculated. A small UV-shift of band gap values regarding that of commercial photo-active TiO2 was detected as consequence of the quantum size effect, suggesting that photocatalytic experiments should be performed under UV-radiation assistance. The synthesized solids showed good activity in the photocatalytic oxidation of a textile dye (reactive yellow 145: RY 145), achieving conversions higher than 70% and chemical oxygen demand removal between 60% and 80%. | 10.1080/09593330.2015.1114031 |
pubmed_227_2576 | BACKGROUND AND AIMS
Statins are considered contraindicated in patients with chronic liver disease. Our objective was to determine the risk of developing hepatotoxicity from statin therapy in hyperlipidemic patients with hepatitis C.
METHODS
Changes in liver biochemistry values within 12 months compared with baseline were determined in 3 cohorts matched for age, sex, and body mass index: (I) 166 anti-hepatitis C virus (HCV)-positive hyperlipidemic veterans who were initiated on statin therapy; (II) 332 anti-HCV-positive veterans who had not received statin therapy; and (III) 332 anti-HCV-negative hyperlipidemic veterans who were initiated on statin therapy. An increase in liver biochemistry values was defined as mild-moderate or severe as proposed in a previous study on statin hepatotoxicity in a non-hepatitis C population.
RESULTS
In patients with hepatitis C, statin therapy (cohort I) was associated with a higher incidence of mild-moderate liver biochemistry value increases compared with those not on statin therapy (cohort II) (22.9% vs 13.3%, respectively, P = .009), but a lower incidence of severe increases (1.2% vs 6.6%, respectively, P = .015). Among patients started on statin therapy (cohorts I and III), the incidence of mild-moderate liver biochemistry value increases (22.9% vs 16.3%, respectively, P = .094), severe increases (1.2% vs 1%, respectively, P = .874), or discontinuation of statin therapy as a result of hepatotoxicity (21.6% vs 9.2%, respectively, P = .147) were similar in hepatitis C-positive and hepatitis C-negative patients.
CONCLUSIONS
Statin therapy was not associated with a higher risk of severe hepatotoxicity in patients with chronic hepatitis C and appeared safe. | 10.1016/j.cgh.2006.03.014 |
pubmed_814_15887 | BACKGROUND
Early referral forms a crucial part in early inflammatory/rheumatoid arthritis (EI/RA) recovery. Delayed decisions to refer can lead to severe incapacity and emotional distress for individuals and family and feelings of lost time. How patients with EI/RA experience early referral decisions in Primary Care is an under explored area and warrants further investigation.
AIM
To explore how patients newly diagnosed with EI/RA experienced their early contacts with Primary Care as they negotiated their journey through the referral process into secondary care.
DESIGN AND SETTING
Qualitative face-to-face interviews with newly diagnosed EI/RA patients.
METHODS
In-depth semi-structured interviews were conducted to explore patients' experiences of referral from first symptoms to General Practitioner referral. All participants were interviewed within 2 weeks of being diagnosed in Secondary Care. Data analysis was conducted using interpretative phenomenological analysis.
FINDINGS
All participants in this study described having experienced struggles with their navigation through Primary Care towards diagnosis and specialist EI/RA services. This struggle comprised five key elements: 'family persuasion', 'lack of continuity in care', 'pushing for referral', 'strained relations' and 'lost time'.
CONCLUSION
The delays experienced by patients when attempting to reach an early referral decision in Primary Care cause frustration for those presenting with EI/RA, partly because they do not feel heard. There is a significant impact on patients and their families when referral to specialist care is delayed. | 10.1002/msc.1546 |
pubmed_275_16382 | It has been recommended that adult patients with a serum creatinine above 150 mumol/l should be referred to a nephrologist for specialist assessment. This study ascertained all patients in Northern Ireland with creatinine above this concentration in 2001 (n = 19 286 ) to see if this triggered referral within the subsequent year. After exclusion of those who were already known to a nephrologist and those who had acute renal failure, it was found that younger patients and diabetic patients were more likely to be referred. There was no difference in referral rates between male and female patients. However, only 6.5% of all non-diabetic subjects and 19% of diabetic patients were referred within 12 months after a first increased serum creatinine test. | 10.1136/jech.2004.026658 |
pubmed_78_2526 | OBJECTIVES
To study the relationship between the expression level of DLC-1 mRNA (located in 8p) and the invasion/metastasis of human hepatocellular carcinoma (HCC).
METHODS
Fifty-one surgical specimens of human HCC were divided into high-invasive and low invasive groups according to their clinicopathological features. DLC-1 mRNA expression was studied in the 51 HCC specimens as well as 5 different metastasis potential cell lines using real-time quantitative PCR (RQ-PCR).
RESULTS
The expression level of DLC-1 mRNA in HCC specimens with high invasiveness was significantly lower than that with low invasiveness (P < 0.05). The expression levels of DLC-1 mRNA were significantly different between non-metastatic (Hep3B and HepG2) and metastatic (MHCC97-H, MHCC97-L and HCCLM3) cell lines (P < 0.05). From MHCC97-L to HCCLM3, with an increase of invasiveness and metastatic potentials, the expression level of DLC-1 decreased correspondingly, and its expression level in HCCLM3 was significantly lower than that in MHCC97-L (P < 0.01).
CONCLUSION
The expression of DLC-1 mRNA may play an important role in inhibiting the invasiveness and metastasis of HCC. | pubmed_78_2526 |
pubmed_30_19583 | An assay for the N-oxide metabolite of a benzazepine drug by fast atom bombardment ionization with tandem mass spectrometric analysis on a triple quadrupole mass spectrometer has been developed and validated for urine and plasma samples. This methodology allows analysis of this metabolite directly in crude sample extracts, without the need for extensive chromatography or sample derivatization. Quantification was accomplished with the use of a stable isotope analog of the analyte as an internal standard, using the selected reaction monitoring mode of operation. | 10.1002/bms.1200120705 |
others_314_112187 | Teeth exert fundamental functions related to mastication and speech. Despite their great biomedical importance, an overall picture of their cellular and molecular composition is still missing. In this study, we have mapped the transcriptional landscape of the various cell populations that compose human teeth at single-cell resolution, and we analyzed in deeper detail their stem cell populations and their microenvironment. Our study identified great cellular heterogeneity in the dental pulp and the periodontium. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar, and that their distinctive behavior could be due to substantial differences between their microenvironments. Our findings suggest that the microenvironmental specificity is the potential source for the major functional differences of the stem cells located in the various tooth compartments and open new perspectives towards cell-based dental therapeutic approaches | 10.1101/2021.02.19.431962 |
pubmed_665_11374 | Optical density of MAP2 immunoreactivity (OD), the ratio between the MAP2 stained area/total test area (area fraction: AF), the total length of MAP2 labeled profiles (TL) and the ratio perimeter/area of the immunostained profiles (pleomorphism index [PI]) were measured by quantitative immunohistochemistry in the brain of rats of different ages. In old rats versus young and adult animals, OD and AF were significantly lower, whereas PI was significantly higher, in dentate gyrus molecular layer, CA1 stratum radiatum and olfactory bulb. These findings lend support to the many converging results on the higher vulnerability to aging of the CNS areas featuring higher plasticity. | 10.1089/rej.2006.9.94 |
pubmed_296_451 | Is a conditioned aversive stimulus necessary in avoidance conditioning? Or is a reduction in the rate of aversive stimulation alone sufficient to generate and maintain an avoidance response? Rats were subjected to an avoidance procedure in which shocks occurred randomly in time, but a response could reduce the overall rate of shock. Fifteen acquisition curves, obtained from 16 animals, showed both immediate and delayed, rapid and gradual increases in response rate; there was no representative acquisition curve. Response rates were directly related to the amount by which the response reduced shock frequency. In extinction, when shock rates were not affected by responding, the response total was inversely related to the amount by which the response had reduced shock frequency during prior conditioning, with as many as 20,000 extinction responses when the shock frequency reduction had been relatively small. Responding on this procedure shows that avoidance conditioning can occur without benefit of either classical exteroceptive stimuli or covert stimuli inferred from the temporal constancies of a procedure. It also shows that reduction in shock rate is alone sufficient to maintain avoidance. | 10.1901/jeab.1966.9-421 |
pubmed_365_15900 | 1. In order to resolve the extent to which presynaptic noradrenergic mechanisms contribute to the anaesthetic-sparing effects of alpha2-adrenoceptor agonists in vivo microdialysis was used to investigate the combined effects of sodium pentobarbitone and imidazol(in)e alpha2-adrenoceptor agonists on extracellular levels of noradrenaline (NA) in the rat frontal cortex. 2. Dialysate levels of NA were markedly reduced by the addition of TTX (2 microM) or by the removal of calcium in the perfusate. These data imply that dialysate NA levels are ultimately dependent on exocytotic release mechanisms from afferent coeruleo-cortical neurones. 3. Systemic administration of sodium pentobarbitone (85 mg kg(-1), i.p.) induced general anaesthesia and reduced NA levels by 92% after 30 min. The restoration of basal levels 90 min later was closely associated with a return of the corneal blink reflex. 4. Basal NA levels in conscious animals were not affected by an intravenous infusion of equally radioactive solutions of either imidazoline (clonidine) or imidazole (mivazerol) alpha2-adrenoceptor agonists. The dose rate employed for each compound was 2 microg kg(-1) h(-1) over 2 h. 5. The co-administration of intravenous clonidine or mivazerol, each at 2 microg kg(-1) h(-1) for 2 h, with sodium pentobarbitone (85 mg kg(-1), i.p.), produced a marked and prolonged reduction in NA efflux. After 2 h, NA levels remained suppressed by 95% (clonidine) and 80% (mivazerol) and animals remained deeply anaesthetized. 6. The accumulation of tritium in brain tissue was 42-73% lower across all brain regions examined after [3H]-mivazerol administration than after [3H]-clonidine administration. Sodium pentobarbitone did not alter the accumulation of tritium in brain tissue after the administration of either alpha2-adrenoceptor agonist. 7. These data demonstrate that alpha2-adrenoceptor agonists potentiate the inhibitory effects of sodium pentobarbitone on extracellular levels of NA in the frontal cortex. Further studies will be necessary to establish a causal role of noradrenergic mechanisms in the potentiation of anaesthesia by selective alpha2-adrenoceptor agonists. | 10.1038/sj.bjp.0702091 |
pubmed_527_22558 | A method based on solid phase extraction followed by derivatization and gas chromatography-mass spectrometry analysis was validated for the determination of bisphenol A (BPA) in canned food products. This method was used to analyze 78 canned food products for BPA. Concentrations of BPA in canned food products differed considerably among food types, but all were below the specific migration limit of 0.6 mg/kg set by the European Commission Directive for BPA in food or food simulants. Canned tuna products had the highest BPA concentrations in general, with mean and maximum values of 137 and 534 ng/g, respectively. BPA concentrations in the condensed soup products were considerably higher than those in the ready-to-serve soup products, with mean and maximum values of 105 and 189 ng/g, respectively, for the condensed soups and 15 and 34 ng/g, respectively, for the ready-to-serve soups. BPA concentrations in canned vegetable products were relatively low; about 60% of the products had BPA concentrations of less than 10 ng/g. Canned tomato paste products had lower BPA concentrations than did canned pure tomato products. The mean and maximum BPA concentrations were 1.1 and 2.1 ng/g, respectively, for tomato paste products and 9.3 and 23 ng/g, respectively, for the pure tomato products. | 10.4315/0362-028x-73.6.1085 |
pubmed_131_6808 | Yeast cell wall, plasma membrane, total spheroplast, and total soluble protein fractions were isolated from exponentially growing Saccharomyces cerevisiae batch cultures. The cell wall, plasma membrane, and soluble protein fractions were obtained by mechanical disruption of intact yeast cells under identical osmotic conditions. Electron micrographs of purified wall fractions appeared free of vesicular membrane contamination and micrographs of plasma membrane vesicles were free of cell wall contamination. Various stages of cell wall purification were monitored by electron microscopy and comparative two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This resulted in the identification of a glycopeptide designated 16w in the cell wall fraction, with an apparent isoelectric point of 5.0 and an apparent molecular weight of 25 000. Protein analyses of soluble and plasma membrane protein fractions failed to detect component 16w. Two-dimensional protein analyses of total cellular homogenates were capable of resolving the cell wall glycopeptide 16w. However, protein separations of spheroplasts formed by glusulase degradation of the cell wall complex did not detect 16w. These observations suggest that component 16w is unique to the cell wall fraction. In addition, comparison of two-dimensional gels of soluble and plasma membrane proteins, with a total cellular homogenate, tentatively identified several polypeptides unique to each of the soluble and plasma membrane fractions. | 10.1139/o80-077 |
others_413_20413 | An unequitable vaccine allocation and continuously emerging SARS-CoV-2 variants pose challenges to contain the pandemic, which underscores the need for licensing more vaccine candidates, increasing manufacturing capacity and implementing better immunization strategy. Here, we report data from a proof-of-concept investigation in two healthy individuals who received two doses of inactivated whole-virus COVID-19 vaccines, followed by a single heterologous boost vaccination after 7 months with an mRNA vaccine candidate (LPP-Spike-mRNA) developed by Stemirna Therapeutics. Following the boost, Spike-specific antibody (Ab), memory B cell and T cell responses were significantly increased. These findings indicate that a heterologous immunization strategy combining inactivated and mRNA vaccines can generate robust vaccine responses and therefore provide a rational and effective vaccination regim | 10.1101/2021.05.17.21257134 |
pubmed_995_2120 | Thirteen patients with interstitial cystitis (detrusor mastocytosis) and 12 other patients with painful bladder disease without mastocytosis collected 24-h urine specimens that were analysed for the major metabolite of histamine, 1,4-methyl-imidazole-acetic-acid (1,4-MIAA), by reversed phase ion-pair high performance liquid chromatography. The median urinary excretion of 1,4-MIAA was 3.34 mg/24 h (range 1.47-4.66) in the patients with detrusor mastocytosis and 1.75 mg/24 h (range 0.18-4.30) in the other patients with a painful bladder (P less than 0.01). It was concluded from this study that patients with a painful bladder and detrusor mastocytosis had a significantly elevated urinary excretion of 1,4-MIAA compared with other painful bladder patients without mastocytosis, whose urinary excretion of 1,4-MIAA was within the normal range (0.72-2.34 mg/24 h). We suggest that the urinary excretion of 1,4-MIAA might be useful in the diagnosis of interstitial cystitis. | 10.1111/j.1464-410x.1987.tb04612.x |
pubmed_573_18386 | In recent years, nanoparticles (NPs) and related applications have become an intensive area of research, especially in the biotechnological and biomedical fields, with magnetic NPs being one of the promising tools for tumor treatment and as MRI-contrast enhancers. Several internalization and cytotoxicity studies have been performed, but there are still many unanswered questions concerning NP interactions with cells and NP stability. In this study, we prepared functionalized magnetic NPs coated with polyacrylic acid, which were stable in physiological conditions and which were also nontoxic short-term. Using fluorescence, scanning, and transmission electron microscopy, we were able to observe and determine the internalization pathways of polyacrylic acid-coated NPs in Chinese hamster ovary cells. With scanning electron microscopy we captured what might be the first step of NPs internalization - an endocytic vesicle in the process of formation enclosing NPs bound to the membrane. With fluorescence microscopy we observed that NP aggregates were rapidly internalized, in a time-dependent manner, via macropinocytosis and clathrin-mediated endocytosis. Inside the cytoplasm, aggregated NPs were found enclosed in acidified vesicles accumulated in the perinuclear region 1 hour after exposure, where they stayed for up to 24 hours. High intracellular loading of NPs in the Chinese hamster ovary cells was obtained after 24 hours, with no observable toxic effects. Thus polyacrylic acid-coated NPs have potential for use in biotechnological and biomedical applications. | 10.2147/IJN.S38749 |
pubmed_55_12530 | Klaus Hierholzer (1929-2007) dissected various functions influenced by steroids in the distal tubule and showed that aldosterone in low doses reversed the sodium and potassium transport defect in adrenalectomized rats, through a rapid activation of Na+,K+-ATPase. Subsequent studies addressed the role of 11-beta-hydroxysteroid oxidoreductase (11-HSD) and showed that the undisturbed functioning of 11-HSD is a prerequisite for selective mineralocorticosteroid regulation of epithelial transport. Another set of original experiments showed that 11-HSD was equally important in the distal colon, thus establishing that the large intestine acts in parallel with the distal nephron. Hierholzer, born in Konstanz on June 8, 1929, was laureated in medicine on May 25, 1954. Subsequently he worked at the Department of Pharmacology of the University of Freiburg, Cornell University with J. F. Pitts, the Department of Medicine of the University of Frankfurt-am-Main, the University of Copenhagen with H. H. Ussing, and the Institute of Physiology of the Freie Universitaet in Berlin where he became full professor and head of the Institute of Clinical Physiology in 1968. He held that position until 1998. He died in Allensbach in the family house on February 27, 2007. Hierholzer was a member of the Naturforscher Leopoldina Academy and of many other scientific societies, including the Academy of Science and Technology in Berlin, and received various awards including an honorary professorship at the University of Naples, the Bezold Medal, the Volhard Medal, the Schoeller/Junkman Award, and the Malpighi Medal (in memoriam). He published nearly 300 papers including various seminal books. Noteworthy also are his papers on the history of physiology of the kidney and acid-base balance. A total of 26 scientists who trained in his laboratory became professors. | pubmed_55_12530 |
pubmed_521_13106 | Ontogenetic changes in the morphology of the mandibular symphysis are described in Archaeolemur so as to infer the functional significance of symphyseal fusion in this subfossil Malagasy lemur. The first regions of the symphysis to show a more complex morphology were the lower and anterior borders of the joint and, to a lesser extent, the lingual borders of the superior and inferior transverse tori. During growth, these regions became increasingly rugose and encroached upon a centrally located, smooth, "oval" region, which may have been a principal pathway for neurovascular structures communicating with the unfused joint. In subadults, the symphysis was completely fused except for the lingual surface of the inferior transverse torus, where a patent suture and potential space were present between dentaries. Thus, in Archaeolemur there was an age- and size-related pattern of increased symphyseal ossification or fusion that was complete by adulthood. The morphology of the interlocking bony processes and the sequence of ossification in the symphysis suggest that increased dorsoventral shear stress during mastication was the most likely determinant of symphyseal fusion in Archaeolemur. The allometric pattern of greater symphyseal fusion may be linked to the presence of relatively greater dorsoventral shear in adults due to an increased recruitment of balancing-side jaw-muscle force. There is little indication that the symphysis of juvenile Archaeolemur was buttressed to resist forces associated with "wishboning" during mastication or vertical bending during incision. Our observations, as well as those of others, suggest that symphyseal fusion in primates occurs initially as a response to increased dorsoventral shear during mastication. Therefore, wishboning stress might only become a major determinant of symphyseal form and function in those taxa that develop a fused symphysis to counter increased dorsoventral shear. | 10.1002/ajpa.1330950106 |
pubmed_121_1626 | This study investigates the relationship between environmental pollution and economic growth in the context of renewable energy in OECD countries using the panel smooth transition regression (PSTR) model for 1995-2018. The study finds the value of the threshold variable, calculated as the share of renewable energy use in total energy consumption, to be 7.825%. In this context, economic growth affects the environment negatively and increases environmental pollution when the share of renewable energy use in energy consumption is below the threshold. When this share is above the threshold, it reduces environmental pollution by affecting the environment positively. In addition, the findings reveal a non-linear inverted U-shaped relationship between the environment and economic growth in the context of renewable energy, and the Environmental Kuznets Curve (EKC) hypothesis is valid. Therefore, the widespread use of renewable energy is a solution to reducing environmental pollution. Accordingly, it is very important for policymakers to both highlight and encourage renewable energy use. Furthermore, countries need to both invest in this area and focus on R&D to increase renewable energy production. | 10.1007/s11356-022-21516-z |
pubmed_472_18927 | Understanding body size-dependent metal accumulation in aquatic organisms (i.e., metal allometry) is critical in interpreting biomonitoring data. While growth has received the most attention, little is known about controls of metal exposure routes on metal allometry. Here, size-dependent Cd accumulation in zebra mussels (Dreissena polymorpha) from different routes were investigated by exposing mussels to A.(111Cd spiked algae+113Cd spiked river water) or B.(111Cd spiked sediments+113Cd spiked river water). After exposure, 111Cd or 113Cd levels in mussel tissue were found to be negatively correlated with tissue weight, while Cd allometry coefficients (b values) were dependent on Cd exposure routes: -0.664 for algae, -0.241 for sediments and -0.379 for river water, compared to -0.582 in un-exposed mussels. By comparing different Cd exposure routes, we found that size-dependent Cd bioaccumulation from algae or river water could be more responsible for the overall size-dependent Cd accumulation in mussels, and the relative importance of the two sources was dependent on mussel size ranges: Cadmium obtained from algae (algae-Cd) was more important in size-dependent Cd accumulation in smaller mussels (tissue dry weight < 5 mg), while river water-Cd became more important in larger individuals (tissue dry weight > 5 mg). In contrast, sediment-Cd contributed only a small amount to Cd accumulation in zebra mussels and may have little effect on size-dependent Cd bioaccumulation. Our results suggest that size-dependent Cd accumulation in mussels could be largely affected by exposure routes, which should be considered when trying to interpret Cd biomonitoring data of zebra mussels. | 10.1016/j.chemosphere.2016.10.128 |
pubmed_688_14220 | The distribution of radioactivity in pallidal tissue blocks incubated in the presence of either a tritiated enkephalin analogue or [3H]-naloxone, was examined using EM autoradiography. The quantitative evaluation was based on the principle of proportional grain counting. The results showed a preferential accumulating of silver grains over dendrites in the enkephalin-labelled tissue. Following naloxone-labelling, a slight enrichment of grains over axonal elements was found. The findings provide ultrastructural support for previous biochemical data which suggested that different types of opiate binding sites have different tissue localizations. | pubmed_688_14220 |
pubmed_762_16832 | The role of regulation as a mediator of the relations between maternal emotional expressivity and children's adjustment and social competence was examined when children (N = 208) were 4.5 to just 8 years old (Time 1, T1) and 2 years later (Time 2, T2). At T2, as at T1, regulation mediated the relation between positive maternal emotional expressivity and children's functioning. When T1 relations and the stability of variables over time were controlled for in a structural equation model, T2 relations generally were nonsignificant, although parents' dominant negative expressivity predicted high regulation. In contrast, in regressions, the findings for parent positive expressivity, but not negative expressivity, held at T2 when T1 variables were controlled. Thus, relations for negative expressivity, but not positive expressivity, changed with age. | 10.1037//0012-1649.39.1.3 |
pubmed_471_21293 | OBJECTIVES
Familial Mediterranean Fever (FMF) is one of the most prevalent periodic fever syndromes; MEFV, the responsible gene for the disease, is in the short arm of chromosome16. In the considerable count of the FMF patients, only one mutation is found in the MEFV and parents, who were the obligatory carriers for that mutation, were asymptomatic. The aim of this study was to evaluate these asymptomatic parents in regard to mutation in MEFV gene and similarity between parents and offspring patients.
METHODS
In this cross-sectional study, asymptomatic parents of FMF patients enrolled the study were referred to periodic fever clinic or pediatric rheumatology clinic of Tehran University of Medical Sciences. The patients should have at least one mutation in MEFV gene and none of them had any family history of autoinflammatory disease. Twelve mutations in MEFV gene were assessed in the parents by Vienna Lab FMF Strip Assay kit by MAS PCR/Reverse hybridization.
RESULTS
Forty-three patients and their parents participated in the study. Sixty-three percent (27) of patients were male. Onset of disease symptoms in 31 patients (72%) was before 4 years of old. Nine (21%) of the patients had homozygote, 16 (37%) compound heterozygote, and 17(40%) heterozygote for MEFV mutation; there was a case of complex alleles mutations (2%). M694V/M694V in 4 patients (9%) was the most homozygote genotype, and M694V/R761H in 4 (9%) and E148Q in 7 (16%) were the most compound heterozygote and heterozygote genotype, respectively. M694V, M680I, and E148Q were the most mutation in the parents. Overall, 41 patients had mutations similar to their parents' mutation, except 2 whose parents had no mutation, but a patient did.
CONCLUSION
It seems that occurrence of new mutations in offspring is not prevalent among FMF patients and there are other reasons for different clinical presentation in similar mutation carriers. On the other hand, in ethnicities with high prevalence of FMF, new mutation in descendant may occur, infrequently. | 10.1155/2018/1902791 |
pubmed_105_3791 | In the present work, the performance of ultra-high molecular weight polyethylene (UHMWPE) barrier nets in marine environments is investigated by Fourier transform infrared spectroscopy, thermogravimetry, scanning electron microscopy, and tensile experiments. The chemical, morphological, thermal stability, and strength changes after aging in salt spray, hygrothermal, and ultraviolet (UV) environments are characterized. An environmental spectrum is designed to simulate a real service environment and predict the service life of UHMWPE. The results show that UV energy can activate UHMWPE molecules and lead to chain breaking, which lowers the breaking strength more efficiently than salt spray. In a hygrothermal environment, the UHMPE fibers bond into clumps, which causes a slight increase in breaking strength after the initial rapid decrease with aging time. The acceleration ratio of the environmental spectrum increases with increasing aging time, which may be caused by the cross-linking and degradation of macromolecular chains in the material. The environmental spectrum given by this work can be used to evaluate performance and predict the service life of UHMWPE barrier nets in marine environments. | 10.3390/ma15165599 |
pubmed_130_2835 | Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown of PLP2 inhibited the growth and metastasis of melanoma cells. In the present work, we studied the antitumor activity of peptide Rb4 derived from protein PLP2. In vitro, Rb4 induced F-actin polymerization, prevented F-actin depolymerization and increased the ER-derived cytosolic calcium. Such effects were associated with necrosis of murine melanoma B16F10-Nex2 cells and with inhibition of the viability of human cancer cell lines. Loss of plasma membrane integrity, dilation of mitochondria, cytoplasm vacuolation and absence of chromatin condensation characterized tumor cell necrosis. Cleavage of PARP-1 and inhibition of RIP1 expression were also observed. In vivo, peptide Rb4 reduced the lung metastasis of tumor cells and delayed the subcutaneous melanoma growth in a syngeneic model. Rb4 induced the expression of two DAMPs molecules, HMGB1 and calreticulin, in B16F10-Nex2. Our results suggest that peptide Rb4 acts directly on tumor cells inducing the expression of DAMPs, which trigger the immunoprotective effect in vivo against melanoma cells. We suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug. | 10.1038/s41598-022-06429-8 |
pubmed_379_19294 | The goal of this study was to establish the exposure parameters that will generate predictable thermally induced lesions in brain. In addition, the accuracy of a theoretical model for prediction of the lesion size was tested. To do this, 160 adult rabbits were sonicated (frequency 0.936 and 1.72 MHz) and then sacrificed at various intervals after the sonications. The results showed that predictable thermal lesions could be induced if the exposure durations were between 0.5 and 2 s. Dimensions of the necrosed tissue volume were roughly predictable by the theoretical calculations based on purely thermal effects. Shorter sonications required higher intensities (above 3700 W cm-2 at 1.72 MHz) resulting in mechanical effects with extensive vascular damage. Lesion size varied more at longer exposures (5 and 10 s), perhaps due to the increased effect of tissue perfusion. As a conclusion, focused ultrasound can be used for destruction of tissues deep in brain without causing undesirable mechanical effects, if the exposure parameters are selected properly. | 10.1016/0301-5629(94)90058-2 |
pubmed_27_21425 | The expression of one member of the bZip superfamily of transcription factors, c-Jun, is known to be induced by axotomy in retinal ganglion cells (RGCs) and is associated with axonal regrowth. This study used immunohistochemistry combined with retrograde labeling to examine the expression of two additional bZip transcription factors (ATF-2 and Fra-2) in identified adult rat RGCs under favorable and unfavorable conditions for axonal regrowth. For unfavorable regrowth conditions, ganlgion cell axons within the optic nerve were cut close to the eye. For favorable conditions, the optic nerve was replaced with an autologous peripheral nerve graft to allow axonal regrowth. At regular intervals, after axotomy alone or in conjunction with graft placement, the expression of these transcription factors was examined in retinal wholemounts using protein-specific antibodies. The strong cytoplasmic expression of Fra-2 seen in unaxotomized RGCs was reduced beginning 24 h after axotomy. Similarly, the strong nuclear expression of ATF-2 seen prior to axotomy was also reduced after axotomy. These reduction persisted in surviving ganglion cells throughout the 3 week study period. One to 6 months after axotomy and peripheral nerve graft placement, identified RGCs with regrown axons showed strong ATF-2 and Fra-2 expression, suggesting a return to basal conditions. These findings support roles for ATF-2 and Fra-2 in the survival and regeneration process of these central nervous system neurons after axotomy. | 10.1016/0169-328x(96)00070-8 |
pubmed_918_99 | Nanostructured coatings of dental implants have shown great potential in overcoming many challenges responsible for implant failure. In this study, nano spray drying technology was utilized to produce novel biocompatible nanocoatings with antibacterial activity. The experiments were applied on titanium discs, which were used as a model material for dental implants. The produced nanocoatings consisted of poly(lactic-co-glycolic acid) as a biodegradable polymer and norfloxacin as a model antibiotic. Scanning electron microscopy results revealed an average particle size ranging between 400 and 600 nm. In vitro release studies showed a biphasic drug release profile with a burst release within the first 48 h, followed by a sustained release phase until the end of the experiment. The antibacterial activity of the nanocoatings was evaluated against Escherichia coli where the norfloxacin loaded nanocoatings achieved up to 99.83% reduction in the number of viable bacterial colonies. Finally, in vitro biocompatibility of the nanocoatings was investigated using mouse fibroblasts (L929) as a standard sensitive cell line for cytotoxicity assessment. Cell proliferation on the surface of the titanium discs was studied using fluorescence microscopy followed by cell counting assay. Both methods confirmed the biocompatibility of the examined nanocoatings. In conclusion, nano spray drying is a promising technique for preparing tailor-made nanocoatings, thereby representing an innovative approach for the surface modification of dental implants. | 10.1016/j.ejpb.2019.03.003 |
pubmed_891_23285 | Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional coregulator that has an important role in the regulation of the immune response. IRF2BP2 has been associated with the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, but its exact role remains elusive. Here, we identified a novel clinical variant, IRF2BP2 c.625_665del, from two members of a family with inflammatory conditions and investigated the function of IRF2BP2 and c.625_665del mutation in JAK-STAT pathway activation and inflammatory signaling. The levels of constitutive and cytokine-induced phosphorylation of STATs and total STAT1 in peripheral blood monocytes, T cells, and B cells from the patients and four healthy controls were measured by flow cytometry. Inflammation-related gene expression was studied in peripheral blood mononuclear cells using direct digital detection of mRNA (NanoString). Finally, we studied the relationship between IRF2BP2 and STAT1 activation using a luciferase reporter system in a cell model. Our results show that patients having the IRF2BP2 c.625_665del mutation presented overexpression of STAT1 protein and increased constitutive activation of STAT1. In addition, interferon-induced JAK-STAT signaling was upregulated, and several interferon-inducible genes were overexpressed. Constitutive phosphorylation of STAT5 was also found to be upregulated in CD4+ T cells from the patients. Using a cell model, we show that IRF2BP2 was needed to attenuate STAT1 transcriptional activity and that IRF2BP2 c.625_665del mutation failed in this. We conclude that IRF2BP2 has an important role in suppressing immune responses elicited by STAT1 and STAT5 and suggest that aberrations in IRF2BP2 can lead to abnormal function of intrinsic immunity. | 10.3390/ph14080797 |
pubmed_855_1617 | Fanconi-Bickel syndrome (FBS), or glycogen storage disease type XI, is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Recently, this disease was elucidated to link mutations in the glucose transporter 2 (GLUT2) gene. Only three mutations in three FBS families have been reported. Therefore, it is important to elucidate mutations in the GLUT2 gene in FBS by answering the question of whether the syndrome is a single gene disease. In this report, we describe two patients in two unrelated families clinically diagnosed with FBS. No mutation in the entire protein coding region of the GLUT2 gene was detected in patient 1, which suggested that no mutation existed in the GLUT2 gene, or that some mutations had affected the expression of the GLUT2 gene. In patient 2, a novel homozygous nonsense mutation (W420X, Trp at codon 420 to stop codon) was detected. These results support the correlation between GLUT2 gene mutation and FBS syndrome. However, many patients must be analyzed to determine whether other genes are involved in FBS. | 10.1007/s100380050013 |
pubmed_993_10204 | The paper provides a general method for estimating age-reporting errors from two consecutive census populations along the lines suggested by Demeny and Shorter (1968). When the true age structures in the two censuses are the same, the general method and the Demeny-Shorter method give identical results. However, the latter method faces increasingly the problem of inconsistency of the results with the underlying sssumptions as the disparity between the age structures becomes more and more significant. The present method is more general in the sense that it always gives consitent results irrespective of the populations under consideration. | pubmed_993_10204 |
pubmed_483_21379 | The changes introduced with Council Directive 2013/59/Euratom will require European Member States adapt their regulations, procedures and equipment to the new high standards of radiation safety. These new requirements will have an impact, in particular, on the radiology community (including medical physics experts) and on industry. Relevant changes include new definitions, a new dose limit for the eye lens, non-medical imaging exposures, procedures in asymptomatic individuals, the use and regular review of diagnostic reference levels (including interventional procedures), dosimetric information in imaging systems and its transfer to the examination report, new requirements on responsibilities, the registry and analysis of accidental or unintended exposure and population dose evaluation (based on age and gender distribution). Furthermore, the Directive emphasises the need for justification of medical exposure (including asymptomatic individuals), introduces requirements concerning patient information and strengthens those for recording and reporting doses from radiological procedures, the use of diagnostic reference levels, the availability of dose-indicating devices and the improved role and support of the medical physics experts in imaging. | 10.1007/s11547-019-01031-x |
pubmed_625_14530 | BACKGROUND AND AIMS
Diet appears to play a pivotal role in symptom generation in Irritable Bowel Syndrome (IBS). First line dietary therapy for IBS has focused on advice concerning healthy eating and lifestyle management. Research recently has focused on the role of a diet low in fermentable oligo-, di-, and mono-saccharides and polyols (FODMAPs), gluten free (GFD) and wheat free (WFD) diets for the relief of symptoms in IBS.
METHODS
A round table discussion with gastroenterologists and dietitians with a specialist interest in dietary therapies in IBS was held in Sheffield, United Kingdom in May 2017. Existing literature was reviewed. PubMed and EMBASE were searched with the MeSH terms irritable bowel syndrome/diet/diet therapy/gluten/low FODMAP in different combinations to identify relevant articles. A consensus on the application of these dietary therapies into day-to-day practice was developed.
RESULTS
Fourteen randomized trials in IBS evaluating the low FODMAP diet (n studies = 9), GFD (n = 4) and WFD (n = 1) were included in this review. The total number of patients recruited from randomized trials reviewed was: n=580 low FODMAP diet (female, n=430), n=203 GFD (female, n=139), n=276 WFD (female, n=215). There was no significant difference in the gender of patients recruited for both the low FODMAP and GFD randomized studies (p=0.12). The response rate in the literature to a low FODMAP diet ranged between 50-76%, and to GFD ranged between 34-71%. Percentage of IBS patients identified as wheat sensitive was reported as 30% in the literature.
CONCLUSION
There are no head-to-head trials to date utilizing the low FODMAP diet, GFD and WFD for dietary treatment of IBS and still a number of concerns for diets, including nutritional inadequacy and alteration of the gut microbiota. The consensus suggests that there is evidence for the use of the low FODMAP diet, GFD and WFD as dietary therapies for IBS; the decision-making process for using each individual therapy should be directed by a detailed history by the dietitian, involving the patient in the process. | 10.15403/jgld.2014.1121.273.avy |
pubmed_920_22632 | Discrimination is a fundamental determinant of health and health inequities. However, despite the high prevalence of discrimination exposure, there is limited evidence specific to Indigenous populations on the link between discrimination and health. This study employs a validated measure to quantify experiences of everyday discrimination in a national sample of Aboriginal and Torres Strait Islander (Australia's Indigenous peoples) adults surveyed from 2018 to 2020 (≥16 years, n = 8108). It quantifies Prevalence Ratios (PRs) and 95% Confidence Intervals (CIs) for wellbeing outcomes by level of discrimination exposure, and tests if associations vary by attribution of discrimination to Indigeneity. Of the participants, 41.5% reported no discrimination, 47.5% low, and 11.0% moderate-high. Discrimination was more commonly reported by younger versus older participants, females versus males, and those living in remote versus urban or regional areas. Discrimination was significantly associated in a dose-response manner, with measures of social and emotional wellbeing, culture and identity, health behaviour, and health outcomes. The strength of the association varied across outcomes, from a 10-20% increased prevalence for some outcomes (e.g., disconnection from culture (PR = 1.08; 95% CI: 1.03, 1.14), and high blood pressure (1.20; 1.09, 1.32)), to a five-fold prevalence of alcohol dependence (4.96; 3.64, 6.76), for those with moderate-high versus no discrimination exposure. The association was of consistent strength and direction whether attributed to Indigeneity or not-with three exceptions. Discrimination is associated with a broad range of poor wellbeing outcomes in this large-scale, national, diverse cohort of Aboriginal and Torres Strait Islander adults. These findings support the vast potential to improve Aboriginal and Torres Strait Islander peoples' wellbeing, and to reduce Indigenous-non-Indigenous inequities, by reducing exposure to discrimination. | 10.3390/ijerph18126577 |
pubmed_765_19368 | OBJECTIVE
This post hoc analysis evaluated long-term efficacy and safety in patients with focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who entered open-label extension (OLEx) studies to receive long-term adjunctive perampanel.
METHODS
Patients aged 12 years and older who completed phase II or III randomized, double-blind, placebo-controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open-label maintenance period (32-424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed.
RESULTS
Baseline characteristics were generally balanced between patients with FBTCS (n = 720) and GTCS (n = 138). Mean (standard deviation) cumulative duration of perampanel exposure was 102.3 (70.3) weeks (FBTCS) and 83.9 (38.4) weeks (GTCS). Retention rates were 50.0% for up to 4 years (FBTCS) and 49.2% for up to 2 years (GTCS). Across OLEx treatment durations, median reductions in seizure frequency per 28 days were 66.7% (FBTCS) and 80.6% (GTCS). Fifty percent and 75% responder and seizure-freedom rates were 59.5%, 45.3%, and 18.4%, respectively (FBTCS), and 72.5%, 51.5%, and 16.7%, respectively (GTCS). Efficacy was sustained for up to 4 years (FBTCS) and up to 3 years (GTCS), even when accounting for early dropouts. TEAE incidence was highest during Year 1 (FBTCS, 85.3%; GTCS, 86.2%); most common were dizziness and somnolence. During Year 1, serious TEAEs were reported in 81 (11.3%; FBTCS) and 10 (7.2%; GTCS) patients. TEAEs were consistent with the known safety profile of perampanel; no new safety signals were identified with long-term treatment.
SIGNIFICANCE
This post hoc analysis suggests long-term (up to 4 years) adjunctive perampanel (up to 12 mg/d) is efficacious and well tolerated in patients (aged 12 years and older) with FBTCS or GTCS. | 10.1111/epi.16573 |
others_31_813 | CIRCADIAN CLOCK-ASSOCIATED1 (CCA1), a well-known central circadian clock regulator, coordinates plant responses to environmental challenges. Its daily rhythmic expression in Arabidopsis (Arabidopsis thaliana) confers host resistance to the caterpillar Trichoplusia ni. However, it is unclear whether CCA1 plays a role in defense against phloem sap-feeding aphids. In this study, we showed that green peach aphid (Myzus persicae) displayed an intrinsic circadian feeding rhythm. Under constant light, wild-type Columbia-0 (Col-0) Arabidopsis plants coentrained with aphids in the same light/dark cycles exhibited greater antixenotic activity than plants preentrained in the opposite cycle from the aphids. Consistently, circadian mutants cca1-1, cca1-11, lhy-21, ztl-1, ztl-4, and lux-2 suffered more severe damage than Col-0 plants when infested by aphids, suggesting that the Arabidopsis circadian clock plays a defensive role. However, the arrhythmic CCA1 overexpression line (CCA1-OX) displayed strong antixenotic and antibiotic activities despite its loss of circadian regulation. Aphids feeding on CCA1-OX plants exhibited lower reproduction and smaller body size and weight than those on Col-0. Apparently, CCA1 regulates both clock-dependent and -independent defense responses. Systematic investigation based on bioinformatics analyses indicated that resistance to aphids in CCA1-OX plants was due primarily to heightened basal indole glucosinolate levels. Interestingly, aphid feeding induced alternatively spliced intron-retaining CCA1a/b transcripts, which are normally expressed at low levels, whereas expression of the major fully spliced CCA1 transcript remained largely unchanged. We hypothesize that posttranscriptional modulation of CCA1 expression upon aphid infestation maximizes the potential of circadian-mediated defense and stress tolerance while ensuring normal plant development. © 2019 American Society of Plant Biologists | 10.1104/pp.19.00676 |
pubmed_663_15927 | D-xylose is a necessary sugar for animals. The xylanase from a mollusk, Ampullaria crossean, was previously reported by our laboratory. This xylanase can degrade the xylan into D-xylose. But there is still a gap in our knowledge on its metabolic pathway. The question is how does the xylose enter the pentose pathway? With the help of genomic databases and bioinformatic tools, we found that some animals, such as bacteria, have a highly conserved D-xylose isomerase (EC 5.3.1.5). The xylose isomerase from a sea squirt, Ciona intestinali, was heterogeneously expressed in Escherichia coli and purified to confirm its function. The recombinant enzyme had good thermal stability in the presence of Mg(2+). At the optimum temperature and optimum pH environment, its specific activity on D-xylose was 0.331 micromol/mg/min. This enzyme exists broadly in many animals, but it disappeared in the genome of Amphibia-like Xenopus laevis. Its sequence was highly conserved. The xylose isomerases from animals are very interesting proteins for the study of evolution. | 10.1093/abbs/gmn013 |
pubmed_217_12472 | To assess HIV disclosure discussions and related sexual behaviors among men who have sex with men (MSM) who meet sex partners online, 28 qualitative interviews with Seattle-area MSM were analyzed using grounded theory methods and themes and behavior patterns were identified. MSM found a greater ease in communicating and could prescreen partners through the Internet. However, no consistent relationship was found between HIV disclosure and subsequent behaviors: some were safer based on disclosure while perceived HIV status led others to risky behaviors. Interventions need to promote accurate disclosure while acknowledging its limitations and the need for men to self-protect. | 10.1080/00918369.2012.665704 |
pubmed_4_2353 | PURPOSE
Acute diverticulitis (AD) is a highly prevalent disease in Spain. Its chronic-recurrent appearance and high rate of relapse mean that it has a major epidemiological and economic impact on our health system. In spite of this, it has not been studied in any great depth. Reassessing its etiopathology, recent studies have observed that it is an inflammatory disease-not, as classic theories had postulated, an infectious one. In the light of these findings, the suitability of antibiotics for its treatment has been reconsidered. At present, however, the evidence for incorporating these findings into clinical practice guidelines remains insufficient.
METHODS
This study was designed to analyse the safety and efficacy of a non-antibiotic treatment for mild AD. Patients with mild AD (grade 0 in the modified Neff classification) who meet the inclusion criteria will be randomly assigned to one of two outpatient treatment strategies: (a) classical treatment (antibiotics, anti-inflammatories and low-fibre diet) or (b) experimental treatment (anti-inflammatories and low-fibre diet). Clinical controls will be performed at 2, 7, 30, and 90 days. We will determine whether there are any differences in the clinical outcome between groups. The main objective is to demonstrate that antibiotics neither accelerate the resolution of the disease nor decrease the number of complications and/or recurrences in these patients, suggesting that their use may be unnecessary.
CONCLUSIONS
The results of this trial will help to optimize and homogenize the treatment of this highly prevalent disease. However, more studies are required before firm changes can be introduced in international clinical practice guidelines.
TRIAL REGISTRATION
The trial has been registered at the ClinicalTrials.gov database (ID: NCT02785549) and the EU Clinical Trials Register database (EudraCT number: 2016-001596-75). | 10.1007/s00384-017-2879-4 |
pubmed_653_3342 | When you see a person's face, how do you go about combining his or her facial features to make a decision about who that person is? Most current theories of face perception assert that the ability to recognize a human face is not simply the result of an independent analysis of individual features, but instead involves a holistic coding of the relationships among features. This coding is thought to enhance people's ability to recognize a face beyond what would be expected if each feature were shown in isolation. In the study reported here, we explicitly tested this idea by comparing human performance on facial-feature integration with that of an optimal Bayesian integrator. Contrary to the predictions of most current notions of face perception, our findings showed that human observers integrate facial features in a manner that is no better than would be predicted by their ability to use each individual feature when shown in isolation. That is, a face is perceived no better than the sum of its individual parts. | 10.1177/0956797611427407 |
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