Human muscle cell denervation: the results of a 31-phosphorus magnetic resonance spectroscopy study.

The results presented here demonstrate that there is a major abnormality of high and low energy phosphate metabolism in muscle following peripheral nerve damage. Using 31-phosphorus magnetic resonance spectroscopy the changes in phosphocreatine, adenosine triphosphate, inorganic phosphate and metabolites of membrane metabolism could be observed in vivo in human subjects. The data indicate that there may be a metabolic myopathy in the muscle cells after nerve injury. Further, the metabolic changes did not always return to the control level, indicating a persistence of the abnormality. This failure of the metabolic function of the cells may be important in determining the ultimate outcome of peripheral nerve surgery.


Educating students with mild handicaps in general classrooms: essential teaching practices for general and special educators.

This study was designed to identify and validate essential teaching practices needed by both general and special educators to successfully educate students with mild handicaps in general classrooms. An interdisciplinary panel of 105 experts, evenly divided into university-based and field-based participants from 35 states, identified 96 of 125 practices in six categories as being essential for effective teaching of mainstreamed students with mild handicaps. Based on a two-round Delphi procedure, a substantial majority (82%) of these teaching practices were seen as being essential for both general and special educators across all six rated categories. Panel ratings were significantly higher for special educators than general educators on four of the six categories. No significant differences in ratings were found for university-based versus field-based panelists, or for field-based panelists who were professionals directly involved in elementary or secondary teaching roles versus administrators, supervisors, and consultants. Based on essential teaching practices validated in this study, implications for preservice teacher preparation and staff development programs for general and special educators are discussed.


Neuro-ophthalmic features of carotid cavernous fistulas and their treatment by endoarterial balloon embolisation.

The neuro-ophthalmic features of 11 traumatic carotid cavernous fistulas and their successful occlusion by endoarterial balloon embolisation is reported. Significant improvement in all neuro-ophthalmic signs and symptoms occurred following treatment, however, ocular motility deficits persisted in 7 patients. All 11 fistulas were occluded and the patency of the internal carotid artery was preserved in 9 patients. Though the internal carotid artery was sacrificed in 2 patients there were no permanent sequelae. Transient complications of the procedure occurred in 2 patients.


Influences of exposure to cigarette smoke on concentration of nicorandil in plasma of rats.

Influences of acute exposure to cigarette smoke on plasma concentrations of nicorandil administered orally and parenterally were investigated in rats by HPLC. The animals were exposed to tobacco smoke of two kinds of cigarettes using a smoking machine (i.e., the cigarette smoke contained either low or high nicotine and tar). The plasma concentration of nicorandil administered orally at a dose of 10 mg/kg had a lower absorption phase in two cigarette smoke-exposed groups, particularly in the high nicotine and tar-containing cigarette smoke-exposed group, compared with the nonsmoking control group. The AUC and MRT values in a high nicotine and tar-containing cigarette smoke-exposed group were lower and higher, respectively, than in the nonsmoking control group. However, there was no marked difference in nicorandil plasma concentrations between the cigarette smoke-exposed group and the nonsmoking control group when nicorandil was administered ip or iv at a dose of 5 mg/kg. These results suggest that cigarette smoke exposure causes the suppression or delay of absorption of nicorandil from the gastrointestinal tract.


Psychosocial factors as predictors for early retirement in patients with chronic low back pain.

The incidence of disability pensions was followed up for an approximate period of 4.5 yr in 476 patients with chronic low-back pain. Most of the psychosocial factors assessed at the beginning of the study predicted subsequent early retirement. In the final logistic regression analysis associations with early retirement were found for self-employment, free-floating anxiety, internal back pain locus of control, beliefs in control by others, and accomplishment of back exercises. An early detection of these factors is emphasized.


Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.

Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer: Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well established that the forebrain cholinergic system, whose integrity is essential for learning and memory functions, depends on the target-derived retrograde messenger nerve growth factor (NGF). Therefore, we measured NGF and choline acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in adult rats that had received a single injection of either STZ or artificial cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One week after ICV STZ treatment, NGF content was significantly decreased (-32%) in the septal region, where NGF-responsive cell bodies are located and NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels in the cortex and hippocampus, which are target regions for the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations in NGF levels were not related to changes in ChAT activity that decreased in the hippocampus by only 15%. This might be due to masking effects exerted by compensatory NGF-mediated stimulation of ChAT activity in remaining functional neurons. It is suggested that impaired behavior which has been observed after STZ-induced impairment of cerebral glucose and energy metabolism may be at least partially related to a diminished capacity of central NGF-responsive neurons to bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)


Electron microscopic study of (A)BC excinuclease. DNA is sharply bent in the UvrB-DNA complex.

Nucleotide excision repair in Escherichia coli is initiated by the UvrA, UvrB and UvrC proteins. UvrA is the damage recognition subunit, makes an A2B1 complex with the targeting subunit UvrB, and the complex binds to the lesion site; UvrA dissociates leaving behind a very stable UvrB-DNA complex that is recognized by the trigger subunit, UvrC, and the ensuing UvrB-UvrC heterodimer makes two incisions, one on either side of the lesion. Using electron microscopy, we investigated the structures of these early A, A-B intermediates on DNA containing ultraviolet light photoproducts. UvrA, which is known to bind to DNA as a dimer and produce a DNase I footprint of 33 base-pairs does not change the trajectory of DNA appreciably. The A2B1 complex clearly shows a bipartite structure and its effect on the trajectory of the DNA was not consistently straight or kinked. In contrast, the DNA in the preincision UvrB-DNA complex appears to be severely kinked; 43% of the molecules are bent by 80 degrees or more, with an average bending angle of 127 degrees. It appears that protein-induced bending is an important step on the pathway leading to excision of the damaged nucleotide by (A)BC excinuclease.


The Monfort operation for abdominal wall reconstruction in the prune belly syndrome.

We present our results in correcting the abdominal wall defect in 8 patients with the prune belly syndrome using the Monfort operation. Mean patient age at operation was 10 years. Four patients also underwent significant concomitant operative procedures. There were no early postoperative complications, and the mean postoperative stay for those 4 children undergoing abdominal wall reconstruction alone was 7.7 days. This operation preserves the umbilicus, and strengthens, flattens and thickens the abdominal wall. It produces a narrow-waisted more normal physique and provides excellent transperitoneal exposure for concomitant genitourinary reconstructive procedures.


Comparison of the host ranges and antigenicity of Cryptosporidium parvum and Cryptosporidium wrairi from guinea pigs.

Oocysts of a Cryptosporidium isolate from guinea pigs were not infectious for adult mice, but were infectious for two of three newborn calves and for suckling mice. However, oocysts isolated from calves or mice infected with guinea pig Cryptosporidium were not infectious for guinea pigs. Four isolates of C. parvum from calves were incapable of infecting weanling guinea pigs. Microscopic examination of tissue from the colon and cecum of suckling guinea pigs inoculated with C. parvum revealed sparse infection of some pups. These host range studies and previously described differences in 125I-labeled oocyst surface protein profiles between Cryptosporidium sp. from guinea pigs and C. parvum suggest they are distinct species. We propose the name Cryptosporidium wrairi be retained. Studies with monoclonal antibodies indicate that C. wrairi and C. parvum are antigenically related.


Laparoscopic general surgery: current status and future prospects.

The capability of performing major abdominal surgery while avoiding a large abdominal incision has clear benefits for patient care. Laparoscopic cholecystectomy can reduce hospital stays and the length of the recovery period, as well as decrease postoperative pain, diminish scarring, and provide significant cost savings.


Compliance and quality in residential life. Quality, organization design, and standards.

Regulations and voluntary standards within the context of organizational design and mission as well as leadership in management for quality were discussed. Rules and regulations are closely associated with the structure and mission of the organization. Altering them may require fundamental redesign of organizational structure and purpose. Likewise, alterations in organizational design can change the need for rules and regulations. In addition, standards do not automatically yield quality. Rather, they define expected levels of performance from individuals, programs, and the organization. The senior management of organizations is responsible for exercising the leadership in managing for quality.


Plasma polyunsaturated fatty acids in liver cirrhosis with or without chronic hepatic encephalopathy: a preliminary study.

Fatty acid levels (from C14:0 to C22:6n3) in plasma lipid fractions were prospectively studied in 11 cirrhotic patients with chronic hepatic encephalopathy and compared with those in 23 cirrhotic patients without chronic hepatic encephalopathy with similar age, sex distribution, and liver and nutritional status, and in 11 age- and sex-matched, healthy subjects. Plasma lipid fractions were separated by thin-layer chromatography and fatty acids were identified by capillary column gas-liquid chromatography. Total n6 polyunsaturated fatty acid plasma levels were lower in cirrhotic patients--with and without chronic hepatic encephalopathy--than in control subjects. In addition, arachidonic acid levels, both in total lipids and fractions, were lower in patients with than in those without chronic encephalopathy. On the other hand, a selective decrease of plasma docosahexaenoic acid (a major component of neuronal membranes) was observed in those patients with chronic encephalopathy as compared with both control and cirrhotic subjects without chronic encephalopathy. These findings may be due to various mechanisms. Differences in long-chain polyunsaturated fatty acid content in fish- and meat-restricted diets partly may account for these findings. However, it could be speculated that polyunsaturated fatty acid biosynthesis may be reduced further in patients with chronic hepatic encephalopathy because of either a decrease in portal essential fatty acid extraction in the postabsorptive phase due to portal-systemic shunting or to the effect of protein-restricted diets. Furthermore, the finding of low plasma docosahexaenoic acid in these patients raises the possibility that this deficiency might be an additional pathogenic factor in chronic hepatic encephalopathy.


Partial protection of 1 alpha-hydroxyvitamin D3 against the development of diabetes induced by multiple low-dose streptozotocin injection in CD-1 mice.

1 alpha-Hydroxyvitamin D3 (1 alpha-OH-D3), a precursor of active vitamin D3, 1 alpha,25-dihydroxyvitamin D3, was tested in CD-1 mice for its in vivo effect against the development of diabetes induced by administering multiple low doses of streptozotocin (STZ). Daily intraperitoneal (IP) injections of 35 mg/kg body weight of STZ administered for 5 consecutive days to mice from 7 weeks of age induced a delayed-onset hyperglycemia, insulitis, and beta-cell degranulation in 26 of 28 mice. Only 12 of 29 mice developed diabetes when treated with simultaneous daily IP injections of 1 alpha-OH-D3 for 14 consecutive days, with diabetes defined as a plasma glucose level greater than 200 mg/dL. A daily dose of 0.3 micrograms/kg 1 alpha-OH-D3 also protected against the development of hyperglycemia in five of 13 mice, whereas 0.2 micrograms/kg 1 alpha-OH-D3 was ineffective, indicating a dose-related effect. Histological study showed that, among the 1 alpha-OH-D3-treated mice, the pancreatic islets of euglycemic mice showed neither massive islet infiltration nor beta-cell degranulation, whereas those of the hyperglycemic mice showed insulitis. However, when diabetes was chemically induced with a single high dose of STZ, the simultaneous administration of 1 alpha-OH-D3 to mice failed to protect against the development of hyperglycemia; all five mice so treated developed hyperglycemia. Their pancreatic islets did not show insulitis. Therefore, it is suggested that 1 alpha-OH-D3 may protect against the development of diabetes following administration of multiple low doses of STZ, probably via an immune mechanism.


The influence of dietary carbohydrate and deferoxamine on developing copper deficiency of rats.

The present investigation was conducted to follow the development of copper deficiency in male rats from weaning (day 0) to day 31 of dietary copper deprivation and to correlate changes in tissue sizes with copper and iron concentrations. Male rats were fed for 31 days from weaning copper-deficient or adequate diets containing fructose or starch. Another copper-deficient group of rats that was fed fructose was treated with deferoxamine. Rats were killed at day 0, 8, 16, 24, and 31 of the study. In general, no correlation could be found between the development of heart hypertrophy, pancreatic and thymic atrophy, and tissue copper concentrations in copper-deficient rats fed fructose. In contrast, in the heart and pancreas a negative correlation existed between tissue size and iron concentration. In addition, anemia preceded heart hypertrophy. Deferoxamine lowered hepatic iron concentrations, ameliorated the anemia, and decreased heart size compared with untreated rats. The data of the present study suggest that tissue atrophy and hypertrophy and the severity of copper deficiency are not solely due to tissue concentrations of iron and/or copper.


Plasma lipoprotein(a) concentration in familial hypercholesterolemic patients without coronary artery disease.

Familial Hypercholesterolemia (FH) is a condition characterized by markedly elevated blood cholesterol, low-density lipoproteins (LDL), and apolipoprotein B-100 (apo B). The molecular basis of this monogenic disease is the defective functioning of the cellular receptor for LDL that recognizes apo B. Lipoprotein(a) [Lp(a)] is a circulating lipoprotein that is structurally related to LDL, as it also contains apo B. To assess the impact of the LDL receptor deficiency on the plasma Lp(a) concentration, we measured Lp(a) in 28 FH patients and in 31 unaffected relatives. Because elevation of Lp(a) concentration in plasma of patients with coronary artery disease (CAD) appears to occur independently from plasma cholesterol levels, to avoid potentially confounding problems, members of the families chosen had no history for the disease. Whereas apo B clearly showed a bimodality of distribution by being significantly higher in the FH patients (166 +/- 38 mg/dL) than in the unaffected relatives (92 +/- 18 mg/dL), Lp(a) concentration did not differ in the two groups of patients (30 +/- 24 mg/dL in the FH patients v 31 +/- 23 in the normolipidemic relatives). Similar results were obtained when only siblings were further considered. We conclude that although Lp(a) is closely related to LDL structurally, its level in plasma is not significantly affected by the LDL receptor activity.


Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a).

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. LDL and apo B levels are often elevated in untreated hypothyroidism and lowered by thyroxine (T4) treatment, probably due to an increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T4 therapy. The mean concentration of LDL decreased significantly (P = .006) from 6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased significantly (P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations remained unchanged (P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during T4 treatment. In both the untreated condition and during substitution therapy, Lp(a) levels were higher in patients than in healthy controls, probably due to a relatively high frequency of the small Lp(a) phenotypes in our patients. Since Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising that Lp(a) is not reduced along with LDL and apo B. These findings suggest that the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones have little, if any, effect on Lp(a).


Alternative histochemical markers for skeletal muscle capillaries: a statistical comparison among three muscles.

Except in thin muscles, the analysis of muscle capillary depends on direct ultrastructural visualization or histochemical identification of the capillaries using stains for basement membrane or reactions for endothelial cell enzymes. The accuracy of existing histochemical methods for detecting capillaries has not been systematically tested, however. The purpose of the present study was to compare muscle capillarity determined by two methods currently in use, Griffonia simplicifolia I lectin (GSI) and ATPase, with two alternative capillary markers, Lycopersicon esculentum lectin (LEA) and MRC OX.43 antigen. Capillarity, expressed as capillaries around fibers (CAF), was determined in the soleus, extensor digitorum longus, and sternomastoid muscles from 4-month-old female rats. The GSI, LEA, and MRC OX.43 capillary markers gave identical results for each muscle, confirming their validity as cytochemical probes. In contrast, the capillary ATPase method gave significantly lower CAF determinations, with a differential effect of preincubations at pH 4.4 vs 4.0. These data suggest that capillary ATPase acid stability varies within the capillary bed. The use of one or more of the alternative capillary markers tested is suggested for studies of muscle capillarity to confirm that binding sites or enzyme activity used for a given probe is expressed under both control and experimental conditions.


Transition time control analysis of a glycolytic system under different glucose concentrations. Control of transition time versus control of flux.

Control and Response Coefficients of transition time have been determined in a rat liver glycolytic system under different glucose concentrations. Results have been compared with the Flux Control and Flux Response Coefficients measured in the same conditions, showing that transition time and flux are different responses of the system, subject to different regulation and control. Control Coefficients of flux and transition time show a very different profile in each condition of glucose concentration assayed. Ratio of Flux Control coefficients of glucokinase over phosphofructokinase at 5 and 20 mM glucose concentration changes from 3.2 to 0.5, while the same ratio in the case of Transition Time Control Coefficients moves from 0.6 to 0.93. Moreover, the absolute values of Transition Time Control Coefficients in glycolytic conditions are one order of magnitude bigger than in gluconeogenic conditions. Values of Response Coefficients also show that the transition time has a bigger sensitivity to changes in glucose concentration than the flux in all conditions assayed, but particularly in glycolytic ones.


Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG.

Type III receptors for IgG (Fc gamma RII; ref. 1), high-affinity IgE receptors (Fc epsilon RI; ref. 2), as well as the T- and B-cell antigen receptors, consist of multiple components with specialized ligand-binding and signal transduction functions. Fc gamma RII alpha (ligand-binding) and gamma (signal-transducing) subunits are expressed in macrophages, a cell type involved in the uptake of antigen, its processing and the presentation of the resulting peptides to major histocompatibility complex class II-restricted T lymphocytes. Here we show that murine Fc gamma RIII, transfected into Fc gamma R-negative antigen-presenting B-lymphoma cells, mediate rapid ligand internalization and strongly increase the efficiency of antigen presentation when antigen is complexed to IgG. Efficient internalization and antigen presentation via Fc gamma RIII did not require the cytoplasmic domain of the ligand-binding alpha-chain, but did require the gamma-subunit. Using chimaeric molecules, we show that gamma-chain contains a signal for receptor internalization and that the mutation of either of the two tyrosine residues present in its cytoplasmic domain prevents efficient internalization and antigen presentation of immune complexes. Thus, associated chains and their tyrosine-containing motif are not exclusively involved in cell activation, but also determine multimeric receptor internalization.


CD21 is a ligand for CD23 and regulates IgE production.

The molecule CD23, a low-affinity receptor for IgE (Fc epsilon R2), is a type II transmembrane molecule expressed on many haemopoietic cell types. CD23 has pleiotropic roles in the control of lymphocyte behaviour, suggesting that CD23 may interact with another ligand in addition to IgE. To identify such a CD23 ligand, we expressed and purified full-length recombinant CD23, incorporated it into fluorescent liposomes and used these as a probe. We report here that fluorescent liposomes carrying CD23 interact specifically with the cell-surface protein CD21, identified as the receptor for Epstein-Barr virus and the complement receptor-2 on B cells, some T cells and follicular dendritic cells. In addition, fluorescent CD23-liposomes were shown to bind to hamster kidney cells (BHK-21) transfected with CD21 complementary DNA. The interaction between fluorescent CD23-liposomes and B cells or CD21-transfected BHK-21 cells was specifically inhibited by anti-CD21 and anti-CD23 monoclonal antibodies. Western blotting analysis revealed that 14C-labelled liposomes carrying CD23, in contrast to anti-CD21 antibodies, reacted with a subtype of CD21 molecules. Triggering of CD21 either with an anti-CD21 antibody or with recombinant soluble CD23 was shown to increase specifically interleukin-4-induced IgE production from blood mononuclear cells. These results demonstrate that the cell-surface protein CD21 is a ligand for CD23 and that the pairing of these molecules may participate in the control of IgE production.


Evidence for a viral superantigen in humans.

Superantigens bind class II major histocompatibility proteins and stimulate powerful proliferative responses of T lymphocytes bearing particular V beta sequences as part of their alpha beta antigen receptor. Exogenous bacterial superantigens are responsible for food poisoning and toxic shock syndrome. Murine virus-encoded self-superantigens induce clonal deletion of T lymphocytes. Although superantigen-like properties have been suggested for human immunodeficiency virus-1, no viral superantigen has been identified in humans. Here we report that the nucleocapsid of the rabies virus is an exogenous superantigen specific for V beta 8 human T lymphocytes which binds to HLA class II alpha-chains.


Atrial and brain natriuretic peptides enhance dopamine accumulation in cultured rat hypothalamic cells including dopaminergic neurons.

Dopamine accumulation in hypothalamic cells by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was analyzed using newborn rat hypothalamic cells in culture. Both ANP and BNP caused a dose-dependent increase in [3H]-dopamine accumulation in the cells. ANP increased [3H]-dopamine accumulation significantly within 20 min. The effects of ANP and BNP on dopamine accumulation paralleled an increase in intracellular cGMP concentration. (Bu)2-cGMP and sodium nitroprusside, a stimulator of the soluble form of guanylate cyclase, also enhanced [3H]-dopamine accumulation. ANP had no effect on efflux of [3H] radioactivity after [3H]-dopamine uptake. These results suggest that a change in cGMP is one of the intermediate steps in dopamine accumulation in hypothalamic cells by ANP and BNP.


Distribution of type I interleukin-1 receptor messenger RNA in testis: an in situ histochemical study in the mouse.

The cytokine interleukin-1 (IL-1) has been reported to inhibit the hypothalamic-pituitary-gonadal axis, both through actions in brain and at the gonadal level. Recently, high affinity binding sites for 125I-recombinant human IL-1 alpha have been identified in the mouse testis with characteristics similar to those of type I IL-1 receptors on T lymphocytes and fibroblasts. The present study employed in situ hybridization histochemistry with 35S-labeled antisense cRNA probes derived from a murine type I IL-1 receptor cDNA to identify type I IL-1 receptor mRNA in the mouse testis. An intense signal was observed over interstitial cells, and over the cytoplasm of the epithelium of epididymal ducts, most prominently in the head region. The signal over seminiferous tubules, and over sperm cells within tubules and epididymal ducts, was comparable to background. This distribution of type I IL-1 receptor mRNA was similar to that recently reported for 125(I)I-IL-1-alpha binding sites, and supports evidence implicating IL-1 as a direct regulator of gonadal function.


Expression of Fc gamma receptors on astroglial cell lines and their role in the central nervous system.

Astrocytes have been regarded as the matrix of the central nervous system and as nutritional, metabolic support to neurons. Recently, immunological roles of astrocytes have been reported, especially in multiple sclerosis and experimental allergic encephalitis. One observation shows that human glioma cells, which lack CD4 molecules, can be infected with human immunodeficiency virus in vitro. Another report described that human macrophages can be infected with human immunodeficiency virus through Fc gamma receptors expressed on their cell surfaces. These results prompted us to examine the functioning molecules, especially Fc gamma receptor for immunoglobulin G, expressed on the astroglial cell line. From erythrocyte-antibody rosette assays, redirected cytolysis and flow cytometric analysis, we have shown that human astrocytoma cell lines possess Fc gamma receptors on their cell surfaces. Furthermore, primary cultured murine astrocytes express Fc gamma II receptors, reacting with 2.4G2 monoclonal antibody. Surprisingly, murine astrocytes prepared from newborn BALB/c mice demonstrate killing activity against allogeneic T cell leukemia by antibody-dependent cellular cytotoxicity. After treatment with the macrophage activating factor, interferon-gamma, expression of Fc gamma receptors and killer activity of astrocytes were augmented. From these results, it is suspected that the astroglial cell lines play an important immunological role in the brain.


Haloperidol-induced increase in neuropeptide Y immunoreactivity in the locus coeruleus of the rat brain.

The effect of haloperidol, a dopamine (preferably D2) receptor blocking agent on neuropeptide Y immunoreactivity was studied immunohistochemically in neurons of the locus coeruleus and striatum of rat brain. It was found that haloperidol given four times (5 and 2.5 mg/kg, i.p.) induced, after 24 h, a significant increase in the level of neuropeptide Y immunoreactivity in the locus coeruleus but not in the striatum. No changes in neuropeptide Y immunoreactivity in studied structures were observed after alpha-adrenergic receptor blocking agent phenoxybenzamine or serotonin-synthesis inhibitor D,L-p-chlorophenylalanine. The results suggest that the content of neuropeptide Y-immunoreactive material in nerve cell bodies of the locus coeruleus is inhibitorally controlled by monoaminergic (may be dopaminergic D2) receptors.


A dopamine D1 receptor antagonist, SCH 23390, selectively blocks vasopressin release after noxious stimuli in the rat.

Effects of a dopamine D1 receptor antagonist, SCH 23390, were investigated on plasma level of vasopressin after stressful stimuli in rats. The antagonist markedly attenuated the increase in plasma level of vasopressin after electric footshocks but not after s.c. injected hypertonic saline. The antagonist, however, did not significantly change the suppressive vasopressin response to fear-related emotional stress, though the drug suppressed motor behavior of the rat during testing period. These data suggest that dopamine D1 receptors play an important role selectively in the facilitatory vasopressin response to noxious stimuli in rats.


Variation in susceptibility of inbred lines of chickens to seven species of Eimeria.

The pattern of oocyst production of 8 inbred lines of chickens was compared for each of the 7 species of Eimeria which infect this host. Both the overall numbers and the pattern of oocyst production differed in the inbred lines, but there was no evidence of prolonged cycling of schizogenic developmental stages. Comparison of the numbers of oocysts produced by the different lines indicates that there may be common genetic factors affecting susceptibility to 6 of the 7 species. Surprisingly there appears to be an inverse relationship between susceptibility to E. tenella and susceptibility to the other species: lines which produced most oocysts of E. tenella produced least oocysts of the other species and vice-versa.


Pulmonary dysfunction after primary closure of an abdominal wall defect and its improvement with bronchodilators.

To determine the extent of pulmonary dysfunction following primary closure of an abdominal wall defect, we obtained pulmonary function tests (PFT) in 11 newborn infants with gastroschisis and 6 with large omphaloceles admitted to a newborn ICU in a children's hospital. Patients were 1 to 30 days of age at the time of the PFT; all required endotracheal intubation and mechanical ventilation for operative procedures or for postoperative ventilatory support. Full-term infants (n = 21) undergoing minor surgical procedures provided comparative measurements. Flow-volume curves were obtained with manual inflation of the lungs followed by forced deflation using negative pressure, or by passive expiration, under sedation and pharmacologic paralysis. Deflation flow-volume curves gave measurements of forced vital capacity (FVC) and maximal expiratory flow at 25% of vital capacity from residual volume (MEF25). Modified passive mechanics technique gave passive expiratory curves that provided measurements of respiratory system compliance (Crs) and resistance (Rrs). Tests were done: within 48 h (period A), 3-7 days (period B), and 8-30 days after surgical repair (period C). Pulmonary function testing after nebulized 0.1% isoetharine (a bronchodilator), to test for bronchial reactivity, began midway during the study period in 15 patients. Preoperative and postoperative tests were obtained in 5 patients. Closure of an abdominal wall defect decreased FVC, Crs, and MEF25 by up to 50% of normal, reference values after surgery (P less than 0.05). FVC and MEF25 approached values of normal infants by 4 weeks, whereas Crs remained 50% lower.(ABSTRACT TRUNCATED AT 250 WORDS)


Atomic force microscopy of single- and double-stranded DNA.

A method has been developed for imaging single-stranded DNA with the atomic force microscope (AFM). phi X174 single-stranded DNA in formaldehyde on mica can be imaged in the AFM under propanol or butanol or in air. Measured lengths of most molecules are on the order of 1 mu, although occasionally more extended molecules with lengths of 1.7 to 1.9 mu are seen. Single-stranded DNA in the AFM generally appears lumpier than double-stranded DNA, even when extended. Images of double-stranded lambda DNA in the AFM show more sharp kinks and bends than are typically observed in the electron microscope. Dense, aggregated fields of double-stranded plasmids can be converted by gentle rinsing with hot water to well spread fields.


U1-U2 snRNPs interaction induced by an RNA complementary to the 5' end sequence of U1 snRNA.

Several lines of evidences indicate that U1 and U2 snRNPs become interacting during pre-mRNA splicing. Here we present data showing that an U1-U2 snRNPs interaction can be mediated by an RNA only containing the consensus 5' splice site of all of the sequences characteristic of pre-mRNAs. Using monospecific antibodies (anti-(U1) RNP and anti-(U2) RNP), we have found that a tripartite complex comprising U1 and U2 snRNPs is immunoprecipitated in the presence of a consensus 5' splice site containing RNA, either from a crude extract or from an artificial mixture enriched in U1 and U2 snRNPs. This complex does not appear in the presence of an RNA lacking the sequence complementary to the 5' terminus of U1 snRNA. Moreover, RNAse T1 protection coupled to immunoprecipitation experiments have demonstrated that only the 5' end sequence of U1 snRNA contacts the consensus 5' splice site containing RNA, arguing that U2 snRNP binding in the tripartite complex is mediated by U1 snRNP.


RNA binding specificity of a Drosophila snRNP protein that shares sequence homology with mammalian U1-A and U2-B" proteins.

We have characterized a recombinant Drosophila melanogaster RNA binding protein, D25, by virtue of its antigenic relationship to mammalian U1 and U2 small nuclear ribonucleoprotein (U snRNP) proteins. Sequence analysis revealed that D25 bears strong similarity to both the human U1 snRNP-A (U1-A) and U2 snRNP-B" (U2-B") proteins. However, at residues known to be critical for the RNA binding specificities of U1-A and U2-B" D25 sequence is more similar to U2-B". Using direct RNA binding assays D25 selected U1 RNA from either HeLa or Drosophila Kc cell total RNA. Furthermore, D25 bound U1 RNA when transfected into mammalian cells. Thus, D25 appears to be a Drosophila homolog of the mammalian U1-A protein, despite its sequence similarity to U2-B".


A new strategy useful for rapid identification of microsatellites from DNA libraries with large size inserts.

Microsatellites are new powerful polymorphic markers used for gene mapping. Their characterization requires that all the sequence surrounding the repeat be known in order to be able to design primers for PCR amplification. However, when using DNA libraries with large cloned inserts, this sequence characterization is not immediately practicable. In this paper, we describe a new strategy, based both on the use of a microsatellite specific probing and on the creation of nested deleted clones with the Exonuclease III, in order to position microsatellites in a range allowing direct sequencing. This method was applied to the screening of a mouse chromosome 19 DNA specific library. In this way, thirteen clones were identified by specific probing and seven were submitted to the nested deletion strategy. Five of them presented microsatellite sequences in specific deleted subclones which were selected and sequenced. Primers were designed for each of them and polymorphism between the genomes of several inbred strain of mouse have been determined. These microsatellites were mapped, three of them to chromosome 19 and two to chromosome 11.


Kinetics of 99mTc-labelled antibodies against CD4 (T-helper) lymphocytes in man.

The availability of radiolabeled anti-CD4 antibodies permitted the study of their kinetic behaviour. Four patients suffering from rheumatoid arthritis were investigated prospectively. Three of them received 250 micrograms of 99mTc-labelled anti-CD4 antibody (MAX.16H5). One patient received in vitro 99mTc-antibody-labelled lymphocytes. 4% of the activity was excreted by the kidneys. From 4 to 24 h the splenic uptake decreased from 7.5 to 4%, the liver uptake increased from 25 to 30% the bone marrow uptake remained about the same 50% and the uptake of a single diseased joint (2%) increased slightly to 2.5%. 15 to 30 min after injection of the antibody a redistribution of labelled cells or antibody from liver and spleen to the circulating blood seemed to occur. The recovery rate (0-1 h) of in vivo labelled cells amounted to 30%, that of in vitro labelled cells to 19%. One patient was examined with in vitro labelled CD4-expressing lymphocytes. There was no difference in the antibody kinetics between in vitro and in vivo labelled cells. The authors suggest that circulating CD4-lymphocytes can be labelled with monoclonal antibodies. The kinetics of these in vitro labelled cells and the injected labelled antibody itself resembles that of recirculating lymphocytes.


[Effect of thermal dehydration on blood levels of volume- regulating hormones and sweat electrolytes in patients with essential hypertension treated with propranolol].

The present study aims to answer the following questions: 1. do secretion of volume related hormones in patients with EH pre- and post treatment with propranolol differ from normotensive subjects if examined in thermal dehydration conditions; 2. is the electrolyte composition of thermal sweat related to the plasma profile of volume related hormones? and 3. does treatment by propranolol influence sweat electrolytes in EH patients. In 15 patients with EH and in 20 healthy subjects a thermal dehydration test was performed. In patients with EH this test was done twice: before treatment and after 6 weeks of propranolol therapy. In all subjects the plasma renin activity (PRA), aldosterone (Ald), AVP and ANP were measured before and after thermal dehydration. In sweat samples collected after 15' and 45' of thermal dehydration (the concentration of Na, K and Cl was assessed). In hypertensive patients before propranolol treatment significantly higher values of PRA, Ald and ANP were found, while sweat concentrations of Na and Cl were significantly lower than in controls. After propranolol treatment sweat electrolytes concentrations showed a tendency to normalize. No significant correlation was found between the plasma hormonal profile and sweat Na, K and Cl concentrations respectively both in controls and patients with EH pretreatment. A significant positive correlation was noticed only in hypertensive patients posttreatment between ANP and sweat potassium concentration respectively, and significant negative correlation between PRA and sweat sodium and chloride concentration. From results obtained in this paper it seemed, that volume related hormones (Ald, AVP, ANP) do not seem to influence markedly the electrolyte composition of thermal sweat both in healthy subjects and in hypertensive patients.


[The role of calmodulin and calcium ions in the immunosuppressive mechanism of the action of cyclosporin A].

The calcium pathway of Cyclosporine A (CyA) action on peripheral blood lymphocytes was assessed with regard to the literature data and self observations of kidney graft recipients. A significant relation between the immunosuppressive action of the drug and intracellular concentrations of Ca2+ is intimately linked with the regulatory potential of calmodulin. Because of the widespread clinical use of calcium channel blockers also considered influence of these drugs on immunosuppression by CyA and their importance in reducing its nephrotoxicity.


[Renovascular arterial hypertension. Evaluation of ultrasonographic measurement of kidney length].

In order to evaluate the ultrasonographic measurement of kidney length, 32 hypertensive patients with renal arterial stenosis treated by intraluminal angioplasty were examined by several ultrasonographies performed by the same observer before and after dilatation. The lack of variation in the contralateral kidney length ascertained the intra-observer reproducibility of the method. We found that ischaemic kidneys were smaller and that this diminution in size depended on the renal arterial lesion (kidneys below atheromatous lesions were of smaller size than those below fibrodysplastic lesions). The increase in size of kidneys treated by angioplasty was most probably due to an increase in perfusion pressure and was to be compared with the results of a separate evaluation of renal function. However, this method has no individual applications in view of the important kidney length distribution at cross-checkings.


[Malaria and hemoglobin S: interactions in African children].

Among 300 cases of Plasmodium falciparum malaria attacks explored in Gabon, the proportion of homozygous (SS) or heterozygous (AS) sickle-cell patients was 6.2 percent in 206 ordinary attacks and 3.2 percent in 94 cerebral malaria attacks, and 23.2 percent in the general population. On the other hand, asymptomatic carriage, as detected in 98 children by thin blood films in school screening, was as frequent in the SS or AS infantile population as in the general population. These data show that haemoglobin S protects effectively, although not entirely, against severe attacks of P. falciparum malaria. The incidence of anaemia and vaso-obstructive crisis in malaria-infested sickle-cell patients suggests that subclinical carriage of haematozoa may worsen the course of sickle-cell disease, and this must be taken into account when planning treatment.


["Spontaneous" ischemic colitis: infectious or medicamentous colitis? 25 cases].

The diagnosis of non-gangrenous ischaemic colitis is difficult to assert when histological findings are not specific and when no precipitating cardiovascular event can be found. The constant absence of relapse after the initial episode suggests that an extraneous triggering event is involved. We have studied retrospectively 25 cases of spontaneous ischaemic colitis, looking for a non-haemodynamic triggering event. At the onset of colitis 9 patients had been taking non-steroidal anti-inflammatory drugs or antibiotics for 2 weeks or less. In 3 other patients colitis was associated with Escherichia coli O157:H7 infection. Striking clinical, endoscopic and histological similarities exist between ischaemic colitis on the one hand and colitis caused by absorption of non-steroidal anti-inflammatory drugs or ampicillin and the colitis reported in E. coli O157:H7 infection on the other hand. Non-steroidal anti-inflammatory drugs and E. coli O157:H7 intestinal infection, possibly facilitated by an antibiotic treatment with e.g. ampicillin, could be either non-haemodynamic triggering factors for ischaemic colitis, or responsible per se for a transient acute colitis with the same characteristics as ischaemic colitis.


[Postmenopausal bone loss. Role of estrogens].

Menopause is attended by an increase in bone remodelling, predominantly resorption, resulting in a trabecular and cortical bone loss which can be prevented by administration of oestrogens. This indicates that oestrogen deficiency is one of the major physiopathological elements of postmenopausal osteoporosis. The mechanism of action of oestrogens has not yet been fully elucidated. The recent finding of functional oestrogen receptors in osteoblasts suggests that oestrogens might have a direct action on bone cells, side by side with their action on the activity or production of calcitropic hormones. The antiresorptive effect of oestrogens might be due to the osteoblasts producing one or several local factors that modulate the differentiation and/or recruitment of osteoclasts. Moreover, animal studies have provided arguments in favour of a direct action of oestrogens on bone formation.


[Painful sequelae of Wallenberg's syndrome].

Twenty-seven out of 45 patients who had Wallenberg's syndrome were re-examined as out-patients. Nineteen were complaining of pain on the side opposite to that with loss or temperature and pain sensations or trigeminal deficit. The follow-up showed that pain was both intense and disabling and its treatment was disappointing. The most striking finding was the high frequency of painful sequelae to Wallenberg's syndrome, since they affected almost one out of two patients. The occurrence of these painful symptoms, usually after lesion of the spinothalamic tract, is difficult to explain.


[Mental disorders in elderly hospitalized patients. Epidemiological study in an internal medicine department].

This epidemiological transversal study conducted on 100 patients older than 65 years hospitalized in the Internal Medicine department of a University hospital demonstrates the frequency of psychiatric pathology in these patients: dementia 19 percent; other psycho-organic disorders 17 percent; affective disorders 23 percent and other psychological disturbances 4 percent. Thus, 63 percent of this patient population had a mental disorder as defined by the DSM III criteria. These disorders are generally not or imperfectly identified by the internists in charge of these patients.


[Castleman's disease. An intrapulmonary isolated form with fissural exteriorization].

We report a well-documented case of Castleman's disease which embodied all the main features of its localized forms, those most frequently described in the literature. This case was particular by its unusual intrapulmonary location and its intra-fissural development, which explains why the diagnosis was not considered preoperatively. A review of the literature showed that beside the localized forms of Castleman's disease multifocal forms have recently been reported; these have a much poorer prognosis, and their treatment has not yet been established.


[Myocardial thallium scintigraphy after administration of dipyridamole. Application to the diagnosis and evaluation of coronary insufficiency].

Myocardial thallium scintigraphy performed after intravenous injection of dipyridamole is a non-invasive method to diagnose and evaluate coronary disease. It can be used as an alternative to postexercise scintigraphy, both methods having similar sensitivity and specificity. The dipyridamole test is contraindicated in patients with a history of bronchospasm and uncontrolled angina pectoris. Close clinical and electrocardiographic monitoring is required. The wide use of tomographic techniques has notably improved this examination.


[Visceral leishmaniasis. Diagnosis by western blotting].

Using Western blotting, antibodies directed against a 94 kiloDalton Leishmania antigen are detectable in the sera of patients with visceral leishmaniasis. The absence of these antibodies in the sera of patients with other leishmaniasis, protozoiases, helminthiases, and fungal or bacterial diseases, makes it a biological marker of visceral leishmaniasis, and gives this method its value in immunodiagnosis.


[Silent exercise-induced enzymatic myopathies at rest in adults. A cause of confusion with fibromyalgia].

Exercise-induced enzymatic myopathies include carnitine palmityl transferase deficiency and, among muscular glycogenoses, Mac Ardle's and Tarui diseases. These diseases are usually recognized when exercise-induced myalgias, myoglobinuria and raised creatinine kinase (CK) levels are present. However, myoglobinuria may be absent in 10 to 50 percent of the cases, and CK levels are often normal at rest; thus, the diagnosis is often delayed for several years, with a risk of acute renal failure in 10 to 30 percent of the patients. We report 6 cases of exercise-induced enzymatic myopathies with normal CK levels and with electromyographic studies at rest. The main clinical features of these cases and those of similar conditions reported in the literature are male sex, onset of the disease before the age of 15 years, episodes of severe exercise-induced myalgias, cramps and muscle weakness and myogenic hyperuricaemia at rest in muscular glycogenosis.


[Ischemic cerebral vascular stroke after heroin sniffing. A new case].

Three hours after sniffing a dose of heroin, a 30-year old man developed right hemiplegia with aphasia. Magnetic resonance imaging of the brain showed an infarct in the territory of the left anterior choroid artery. Cerebral vascular accidents occurring as complications of heroin addiction are rare: a review of the literature yielded only 13 documented cases. The main characteristics of these strokes are analysed and their pathogenetic mechanisms (immuno-allergic vasculitis, vascular spasm) are discussed.


[Apolipoprotein C-III in nephrology].

Apolipoprotein C-III is synthesized by the liver and the small intestine. It inhibits the actions of lipoprotein lipase and hepatic triglyceride lipase. An increase of plasma apolipoprotein C-III levels has been found in patients with renal failure, in those under haemodialysis and in renal transplant recipients. The consequences of this increase correlate with the hypertriglyceridaemia observed in these patients. The responsibility of hormonal or non-hormonal factors that modulate the metabolism of apolipoprotein C-III is discussed in order to help in the understanding of the physiopathological mechanisms of lipid disorders in these renal diseases.


[Postmenopausal bone loss. Role of progesterone and androgens].

Oestrogen deficiency is the main physiopathological factor of postmenopausal osteoporosis. The repercussions on bone metabolism of decrease in other sex steroid levels (progesterone, androgens) remains imperfectly known. Several studies on both animals and man have demonstrated that androgens and progestogens derived from testosterone have an anabolic effect on bone tissue. The latest data from studies conducted in non-menopausal women treated with progesterone suggest that this hormone might prevent bone loss. The mechanism of action of this effect on cells remain to be determined, even though progesterone has been shown to exert a mitogenic activity in vitro. Altogether, these data suggest that side by side with oestrogen deficiency the decrease of other sex steroid levels might also play a role in the physiopathology of postmenopausal bone loss.


Prevention of hyperglycemia improves the long-term result of islet transplantation in streptozotocin-diabetic rats.

We examined the hypothesis that prevention of hyperglycemia during the critical period immediately following islet transplantation will improve the outcome of the transplantation in streptozotocin-diabetic rats. Two days after intravenous injection of streptozotocin (70 mg/kg), 400 or 1,000 islets were transplanted into the left kidney subcapsular space. A group of rats transplanted with 400 islets was treated with insulin from 1 day before transplantation and for 7 days. Intravenous glucose infusion was performed at 10 days and 3 months after transplantation. In addition, at 3 months, the grafts were examined by light and electron microscopy. We found that rats transplanted with 400 islets without any concomitant insulin administration remained diabetic throughout the 3-month period and no plasma insulin response was induced by glucose infusion in these rats. In contrast, diabetic rats transplanted with 400 islets and treated with insulin for 7 days remained normoglycemic throughout the 3-month period, as did rats transplanted with 1,000 islets. Furthermore, these rats had normal glucose-stimulated insulin secretion both at 10 days and at 3 months after transplantation. Moreover, islet grafts from rats transplanted with 400 islets and administered insulin as well as from rats transplanted with 1,000 islets were morphologically normal, and following removal of the graft, hyperglycemia developed rapidly. In contrast, the islet grafts from rats transplanted with 400 islets without concomitant insulin administration had only few insulin cells. Thus, by preventing hyperglycemia at the time of islet transplantation, the long-term result of islet transplantation was improved. Therefore, the ambient glucose level initially following islet transplantation is critical for the long-term result.


Intracerebroventricular administration of a specific IL-1 receptor antagonist blocks food and water intake suppression induced by interleukin-1 beta.

Intracerebroventricular (ICV) microinfusion of recombinant human interleukin-1 beta (rhIL-1 beta, 1.0 ng/rat) suppressed the short-term (2 h) food and water intakes in rats. ICV infusion of recombinant human IL-1 receptor antagonist (rhIL-1ra) had no effect on food or water intake. Concomitant ICV infusion of rhIL-1 beta (1.0 ng/rat) and increasing concentrations of rhIL-1ra (25 to 1000 ng/rat) resulted in a dose-dependent inhibition of the short-term food and water intake suppression induced by rhIL-1 beta. The highest doses of rhIL-1ra (500 and 1000 ng/rat) completely blocked the food and water intake suppression induced by rhIL-1 beta. This suggests specificity of IL-1 beta suppression of short-term feeding and drinking by a direct action in the central nervous system (CNS). This ability of rhIL-1ra may have potential therapeutic implications in acute and chronic pathological processes associated with increased levels of IL-1 and appetite suppression.


Effects of dexamethasone on the development of radiation nephropathy in the rat.

Low-dose, chronic administration of the synthetic glucocorticoid, dexamethasone, to male CD-I rats in the drinking water or by osmotic minipumps implanted subcutaneously after supralethal irradiation of the kidneys (20 Gy) was studied. The effectiveness of treatment with dexamethasone in the drinking water at concentrations of 23 micrograms/l to 188 micrograms/l and treatment times varying from 33 to 166 days was evaluated. At monthly intervals kidney function was assayed by measuring the clearance of 51Cr-ethylenediaminetetraacetic acid. All dexamethasone treatment regimens increased survival times significantly and delayed the development of kidney dysfunction. The most effective combination of concentration of dexamethasone in drinking water and treatment interval after irradiation with respect to survival was 94 micrograms/l and 88 days. However, a slightly longer survival and a better functional result was obtained if an equivalent amount of dexamethasone was administered by minipumps. Shielding the adrenal glands during kidney irradiation did not prolong survival. This shows that the beneficial effect of dexamethasone is not due to compensation for reduced adrenal glucocorticoid production resulting from concomitant exposures of these glands during kidney irradiation.


Vascular response to fractionated irradiation in the rat lung.

The effects of fractionated hemithorax irradiation on normal lung tissue were examined by measuring changes in the vascular permeability surface area product (PS) and relative lung blood flow in Sprague-Dawley rats. The rats received five daily fractions per week of either 3.0 or 4.0 Gy for 4 weeks to the left lung. Between 3 and 5 weeks after the start of irradiation, the average PS was approximately 50% above normal for the group of rats that received 3.0 Gy/day and 200-300% above normal in the group of rats that received 4.0 Gy/day. Treatment with cyproheptadine, indomethacin, or theophylline had no effect, but treatment with dexamethasone significantly reduced PS to near normal levels. Left-to-right blood flow ratios in the group of rats that received 3.0 Gy/day decreased to 66% of normal levels by 4 weeks. In the group of rats that received 4.0 Gy/day, blood flow decreased to 46% of normal levels by 4 weeks. Treatment with dexamethasone maintained normal blood flow until the drug dose was reduced. These results agree with earlier studies using single-dose irradiation and indicate that the methods used to measure PS and blood flow are sensitive at low doses.


Impact of chronic illness in children on parental living conditions. A population-based study in a Swedish primary care district.

In a geographically defined child population aged 0-15, every twelfth child suffered from chronic illness. Their parents and randomly selected control children's parents were asked about their living conditions using questionnaires. Non-responders (30%) had the same sociodemographic profile as responders. The socioeconomic level in index families (n = 95) was lower than in control families (n = 166). Both parents worked fewer hours in index than in control families. Index mothers had more health problems and sick days than control mothers. The parents' social relations were most hampered by having children with allergic disorders or mental retardation. Despite reduced hours, more absence from work to care for sick children, and reduced leisure activities, two thirds of the parents of moderately/severely disabled children found it difficult to cater adequately to the needs of their child. A family approach is recommended to provide comprehensive care of children with chronic illness, in which both specialized and primary care are needed.


The relationship between verbal ability and sentence-based speechreading.

Eighteen hearing-impaired subjects participated in the present study. The purpose was to investigate one general question: The nature of the relationship between verbal ability and speechreading. Verbal ability was assessed by two types of measure: a test of vocabulary size, and four tests of lexical access speed. The results demonstrated that lexical access speed was related to speechreading performance. Vocabulary size was not found to be directly related to the speechreading criterion; rather, its influence was in an indirect fashion via its relation to lexical access speed. It was concluded that lexical access speed could be used as a diagnostic tool, such that when an individual demonstrates lexical access that is unreasonably slow, it could be taken as an indication to suggest that rehabilitation programs should emphasize alternatives to speechreading. A general implication of the present results is that absence of relation between a predictor variable and the speechreading criterion does not necessarily imply absence of relation between the two. There is still a possibility that the predictor variable might be indirectly related to the speechreading criterion.


White blood cells in infants with congenital toxoplasmosis: transient appearance of cALL antigen on reactive marrow lymphocytes.

Existing serological methods for diagnosing congenital toxoplasmosis are inadequate. We have therefore characterized the features of peripheral blood cell counts and smears in a prospective study of 8 affected infants during their first year of life. Enlarged, vacuolated lymphocytes were observed in all patients. Six patients had periods of neutropenia; in 1 patient the neutropenia was severe and prolonged. A bone marrow aspirate from this patient showed enhanced myelopoiesis, and after stimulation with hydrocortisone, but not with adrenaline, his neutrophil count normalized. Phenotyping of his bone marrow cells revealed that approximately 55% of both the immature and mature B lymphocytes were positive for the cALL antigen. Of the 8 patients, 6 had mild eosinophilia, 4 had mild monocytosis and 3 had increased numbers of plasma cells in the peripheral blood. These findings may reflect the activity of the congenital toxoplasma infection and may thus contribute to the diagnosis, particularly in patients with silent serology.


[Peak flow profile and expert testimony. The significance of peakflow self assessment for pneumological expert testimony].

Quantitative assessment of pulmonary obstructive diseases, such as asthma, may be difficult because of variability of obstruction. This is particularly true with regard to expert evidence pulmonary physicians deliver to insurances. Severity of obstruction, degree of impairment by an obstructive ventilatory defect, and temporal relationship of bronchial obstruction to exposure, may not be detected by physiological measurements in the pulmonary function laboratory. Much of the expert's opinion on these matters will depend on the credibility he assigns to the insured individual. The insured individual, in the other hand, has no other proof available than the description of his complaints, which puts him at a disadvantage. Serial peak flow measurements can be instrumental in clarifying such issues. They add an objective dimension to the case history. Six cases in which expert evidence was commissioned by insurances are described in detail, to exemplify how the thinking of the experts was modified by peak flow profiles. The greater usefulness of serial peak flow measurements in occupational asthma is emphasized and problems that may arise with peak flow measurements are discussed.


Photodynamic therapy for thoracic malignancies.

Photodynamic therapy (PDT) is an experimental form of cancer therapy which employs photoactivation of a sensitizing chemical by light of a given wavelength via the production of toxic oxygen species. PDT causes local destruction of cancer, and relies on a therapeutic index between normal and malignant tissue since the latter seems to selectively retain the sensitizer. PDT has both direct tumoricidal effects as well as indirect effects on tumor vasculature causing an early hemorrhagic necrosis of tissue. The treatment has been used for the treatment of endobronchial obstruction by primary and metastatic tumors. Most recently, trials are being performed to evaluate this therapy as a surgical adjunct in the treatment of pleural malignancies such as mesothelioma.


Access to ambulatory care among noninstitutionalized, activity-limited persons 65 and over.

This study examined the impact of income and insurance type on ambulatory care contact use by persons 65 and over who expressed a limitation in their activity. This large group (39% of noninstitutionalized older persons in 1984) had significantly more health problems and ambulatory care contacts than persons not activity-limited. The only previous study on equity in use of physician services among elderly in poorer than average health found relatively little inequality of use due to income and insurance. This study came to the opposite conclusion. Activity-limited persons without Medicare private supplementary insurance, as well as those with supplementary insurance in the bottom and middle of the income distribution, had 15-32% fewer ambulatory care contacts than activity-limited persons with higher income and private supplementary insurance. Particularly striking were the declines in consumption among middle income persons relative to the reference group, indicating that the issue of equity in consumption of health services among older disabled persons affects a much broader group than only the poor and near-poor.


Preactivation: a new concept for generation of photoproducts for potential therapeutic applications.

Controlled exposure of photoactive compounds to light prior to their use in biological targets results in the formation of heretofore unknown photoproducts. This process of photoproduct generation, termed preactivation, renders the photoactive compound capable of systemic use without further dependence on light. We have demonstrated that preactivated Merocyanine and preactivated Photofrin-II possess significant antitumor and antiviral activity against certain tumor cells and viruses, while under identical conditions normal cells and tissues are minimally affected. Thus, the preactivation procedure may represent a promising therapeutic modality for controlling systemic malignancies and viral infections.


Recombinant interleukin-1 receptor antagonist (IL-1ra): effective therapy against gram-negative sepsis in rats.

Morbidity and mortality from bacterial sepsis remain high despite aggressive diagnostic and therapeutic intervention. Interleukin-1 has been implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis. The current experiments were designed to evaluate the therapeutic efficacy of a human recombinant interleukin-1 receptor antagonist (IL-1ra) against polymicrobial gram-negative septicemia in rats. Male rats underwent placement of indwelling carotid arterial and superior vena caval catheters followed by cecal ligation and puncture (CLP). After 3 hours rats received either IL-1ra (10 mg/kg intravenous bolus followed by 5 mg/kg/hr) or an equal volume of vehicle intravenously for 24 hours. Heart rate, respirations, mean arterial blood pressure, and temperature were recorded at frequent intervals, and survival was assessed for 30 hours after CLP. There were no differences in vital signs between groups at baseline or before treatment, and all animals appeared ill with huddled posture, piloerection, and hyperventilation. Twenty-four hours after CLP, IL-1ra significantly ameliorated bradycardia (p = 0.01), hypothermia (p = 0.001), and hypotension (p = 0.05), and 30-hour survival was significantly improved (71% vs 20%, p less than 0.05). IL-1ra lessens the acute hemodynamic, hypothermic, and mortal effects of gram-negative sepsis induced by CLP in rats. These data suggest that IL-1 receptor blockade may be an important new treatment strategy against overwhelming bacterial sepsis.


Up-regulation of prolactin gene expression and feedback modulation of lymphocyte proliferation during acute allograft rejection.

Although recent evidence suggests that prolactin is important in the immune response, bidirectional communication between prolactin and the immune system has not been demonstrated previously. We examined our hypothesis that this communication exists during mouse skin allograft rejection. Serum prolactin levels were measured by bioassay, and pituitary prolactin mRNA was examined by use of Northern blots, in BALB/c mice receiving skin allografts from C57BL mice, on days 2, 4, and 6 after grafting. The feedback effects of prolactin on splenic lymphocytes were assessed in one-way mixed lymphocyte reactions, with or without added interleukin-2 (IL-2) or IL-4. Prolactin mRNA was increased significantly in grafted animals compared with sham animals (2.4-fold by day 4). Serum prolactin bioactivity was also elevated on all days tested. Prolactin treatment resulted in dose-dependent modulation of the mixed lymphocyte reaction with lymphocytes from grafted animals but not from sham animals. These effects depended on the time points and the presence of IL-2 or IL-4; the maximal enhancement occurred with day-4 lymphocytes cultured with IL-4 (80%). This report is the first to implicate in vivo immune regulation of prolactin gene expression. Our observations indicate that bidirectional interaction exists between prolactin and the immune system and provide a rationale for altering prolactin levels to treat allograft rejection.


Effects of microsomal enzyme inducers upon UDP-glucuronic acid concentration and UDP-glucuronosyltransferase activity in the rat intestine and liver.

This study was conducted to evaluate UDP-glucuronosyl-transferase (UDP-GT) activity, UDP-glucuronic acid (UDP-GA) concentration, and UDP-glucose (UDPG) concentration in the rat intestine and liver following oral administration of butylated hydroxyanisole (BHA), benzo[a]pyrene (BaP), 3-methylcholanthrene (3MC), phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or trans-stilbene oxide (TSO). Microsomal UDP-GT activity was assayed in vitro with acetaminophen (AA), harmol (HA), and 1-naphthol (NA) as the aglycones. Intestinal HA and AA glucuronidation were enhanced by BHA, BaP, and TSO, whereas 3MC, PB, PCN, and TCDD augmented hepatic HA-glucuronide formation and BHA, PB, PCN, TCDD, and TSO significantly increased hepatic AA glucuronidation. All inducing agents except PB and PCN markedly increased both intestinal and hepatic NA glucuronidation. PB, PCN, and TCDD paradoxically decreased intestinal glucuronidation of AA and HA. A similar effect upon hepatic glucuronidation was not observed with any of the agents studied. Hepatic UDP-GA concentration was increased significantly by all inducers studied except PCN and TCDD, whereas hepatic UDPG concentration was increased only by BHA. In the intestine, significant increases in UDP-GA concentration were produced only by BHA and BaP, which also elevated intestinal UDPG. These results demonstrate that microsomal enzyme inducers evoke different effects upon intestinal and hepatic glucuronidation. These differences are manifested with regard to induced changes in UDP-GT activity as well as treatment-induced alterations in UDP-GA content. Thus, the present study further underscores the marked variance of intestinal and hepatic xenobiotic glucuronidation.


[Atrial natriuretic peptide. Mechanisms of its action].

A survey of the mechanisms of stimulation of secretion and of atrial natriuretic peptide (ANP) and its action is presented. Action of this hormone is particularly important on the kidney, the cardiovascular system and on some endocrine tissues. Major secretory organs are atrial myocytes, with an increased intra-atrial pressure as the stimulus. Under the action of ANP occurs dilatation of arterial blood vessels, often masked in vivo by a secondary increase in the sympathetic tone. ANP decreases the venous return with consecutive lowering of cardiac output. In a kidney an increase in diuresis and natriuresis occurs. Among the actions on the endocrine tissues inhibition of aldosterone secretion and, most probably, inhibition of renin secretion, are the most important.


Evaluation of a monoclonal blocking ELISA and IHA for antibodies to Mycoplasma hyopneumoniae in SPF-pig herds.

A monoclonal blocking enzyme-linked immunosorbent assay (ELISA) and an indirect haemagglutination assay (IHA) were applied to serum samples from 124 specific pathogen-free (SPF) breeding and multiplying herds, which participate in the routine serological surveillance of the Danish SPF programme. Clinical and pathological observations of the herds and microbiological culturing of Mycoplasma hyopneumoniae were used to calculate herd sensitivity, herd specificity and herd predictive values for the two serological assays. The ELISA was superior to the IHA in herd sensitivity and herd specificity, with values of 93 per cent and 96 per cent, respectively, for the ELISA, and 61 per cent and 92 per cent for the IHA. During the six month period of evaluation 2.5 per cent of the herds were infected with M hyopneumoniae each month. At this level the IHA was found to have a positive herd predictive value of 16 per cent, compared with 39 per cent for the ELISA. The negative herd-predictive value on the same level was 99.8 per cent for the ELISA and 98.9 per cent for the IHA. If the assays were applied to a group of herds with a herd prevalence of M hyopneumoniae infection of 30 per cent (as is the case with the production herds in the Danish SPF programme) the predictive value of a positive herd diagnosis would be 91 per cent for the ELISA and 76 per cent for the IHA, and the predictive value of a negative herd diagnosis would be 97 per cent with the ELISA and 85 per cent with the IHA.(ABSTRACT TRUNCATED AT 250 WORDS)


Nuclear and nucleolar targeting signals of Semliki Forest virus nonstructural protein nsP2.

Semliki Forest virus nonstructural protein nsP2, when expressed in the absence of other viral proteins, is transported into the nucleus, with a specific enrichment in nucleoli. This implies that information for its nuclear targeting must be in nsP2 itself. To define the nuclear and nucleolar targeting signals of nsP2, a series of in-frame deletions were made in its coding sequence. We have identified one amino-terminal (residues 25-110) and another carboxy-terminal (residues 634-661) deletion, both of which rendered nsP2 cytoplasmic. The carboxy-terminal region had a pentapeptide sequence P 648R RRV, which resembles some of the known nuclear localization signals. When the three arginines were substituted with aspartic acids, the mutant nsP2 was localized in the cytoplasm. Especially arginines 648-649 were shown to be critical. The carboxy-terminal 232 amino acid residues of nsP2 were able to translocate beta-galactosidase to the nucleus as a fusion protein, whereas the amino-terminal 110 residues failed to do so. Studies with different beta-galactosidase-nsP2 fusions showed that the pentapeptide is necessary for nuclear transport but that its activity is strongly affected by the context. The deletion analysis indicated also that the nuclear localization signal was not sufficient for nucleolar targeting of nsP2. The nucleolar targeting sequence of nsP2 was tentatively mapped between residues 470 and 539, and at least residues 470-489 are an essential part of it.


Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus.

To determine the factors governing inactivation and neutralization, physical, chemical, and biological assays were performed on a molecular clone of human immunodeficiency type 1 (HIV-1HXB3). This included quantitative electron microscopy, gp120 and p24 enzyme-linked immunosorbent assays, reverse, transcriptase assays, and quantitative infectivity assays. For freshly harvested stocks, the ratio of infectious to noninfectious viral particles ranged from 10(-4) to 10(-7) in viral stocks containing 10(9) to 10(10) physical particles per milliliter. There were relatively few gp120 knobs per HIV particle, mean approximately 10 when averaged over the total particle count. Each HIV particle contained a mean approximately 5 x 10(-17) g of p24 and approximately 2 x 10(-16) g of RNA polymerase, corresponding to about 1200 and 80 molecules, respectively. The spontaneous shedding of gp120 envelope proteins from virions was exponential, with a half-life approximately 30 hr. The loss of RNA polymerase activity in virons was also exponential, with a half-life approximately 40 hr. The physical breakup of virions and the dissolution of p24 core proteins were slow (half-life greater than 100 hr) compared to the gp120 shedding and polymerase loss rates. The decay of HIV-1 infectivity was found to obey superimposed single- and multihit kinetics. At short preincubation times, the loss of infectivity correlated with spontaneous shedding of gp120 from virions. At longer times, an accelerating decay rate indicated that HIV requires a minimal number of gp120 molecules for efficient infection of CD4+ cells. The blocking activity of recombinant soluble CD4 (sCD4) and phosphonoformate (foscarnet) varied with the number of gp120 molecules and number of active RNA polymerase molecules per virion, respectively. These results demonstrate that the physical state of virions greatly influences infectivity and neutralization. The knowledge gained from these findings will improve the reliability of in vitro assays, enhance the study of wild-type strains, and facilitate the evaluation of potential HIV therapeutics and vaccines.


The effects of medroxyprogesterone acetate and ethinylestradiol on hemogram, prostate, testes, and semen quality in normal dogs.

Three dogs were treated with medroxyprogesterone acetate (MPA) and three were treated with ethinylestradiol. The results indicate that at a dosage of 3-4.8 mg/kg b.w. MPA does not have any detrimental effects on hemogram, testicles or semen quality, whereas ethinylestradiol (2 micrograms/kg b.w./day) can negatively affect both testes and semen quality. Both drugs can cause a decrease in prostatic size in clinically healthy dogs. Measurements of peripheral serum testosterone levels indicate that at the dosages used, testosterone levels are depressed considerably more by ethinylestradiol than by MPA.


Spontaneous in vitro megakaryocyte colony formation in primary thrombocythemia: relation to platelet factor 4 plasma level and beta-thromboglobulin/platelet factor 4 ratio.

Seventeen patients with primary thrombocythemia (PT) were evaluated for in vitro bone marrow megakaryocyte progenitors (CFU-MK) using a plasma clot system. The aim of this study was to find out whether spontaneous growth of CFU-MK could be used in the diagnosis of PT. The number of CFU-MK was normal in 7 patients and reduced in 10 patients. In the absence of stimulating factor, CFU-MK grew spontaneously in 12 patients, while in 5 patients no spontaneous CFU-MK were observed. The mean plasma level of platelet factor 4 (PF4) was significantly higher (p less than 0.05) in patients without spontaneous CFU-MK (59.8 +/- 59.6 IU/ml; mean +/- SD) compared to patients with (18.1 +/- 20.7 UI/ml). The mean plasma level of beta-thromboglobulin did not differ between patients with or without spontaneous CFU-MK. The beta-thromboglobulin/PF4 ratio was significantly higher (p less than 0.01) in patients with spontaneous CFU-MK (9.9 +/- 7.1) compared to patients without (3.1 +/- 1.4). These results suggest that PF4 could inhibit in vitro spontaneous growth of CFU-MK.


Establishment of the primary structure of the major lipid-dependent Ca2+ binding proteins of chicken growth plate cartilage matrix vesicles: identity with anchorin CII (annexin V) and annexin II.

Electron microscopic studies of calcifying vertebrate tissues reveal the locus of de novo mineral formation within matrix vesicles (MV). The direct involvement of MV in the initiation of mineral formation is supported by the fact that MV isolated from avian growth plate cartilage rapidly accumulate large amounts of Ca2+ and P(i) and induce mineral formation. Exploration of the constituents of MV has revealed two major protein components, a 33 and a 36 kD protein, the former of which binds to cartilage-specific collagens. These annexin-like proteins bind to acidic phospholipids in the presence of submicromolar levels of Ca2+. Antibodies raised against both the purified 33 and the 36 kD MV annexin do not cross-react with the other, indicating that they are distinct proteins. Reported here are studies elucidating the primary structure of both MV proteins using both conventional protein and molecular biologic methods. These studies establish that the 33 kD protein is nearly identical to anchorin CII (annexin V) and that the 36 kD protein is identical to avian annexin II. Immunolocalization studies show that hypertrophic chondrocytes at the calcification front of avian growth plate contain the highest level of these annexins. Further, immunogold labeling indicates that the annexins are localized within MV isolated from the growth plate. Recent studies indicate that annexin V is a new type of ion-selective Ca2+ channel protein that possesses selective collagen binding properties. Since MV are tightly associated with the collagen- and proteoglycan-rich matrix, it is tempting to speculate that this MV protein may be a component of stretch-activated ion channels that enhance Ca2+ uptake during mechanical stress.


Results of directional atherectomy of primary atheromatous and restenosis lesions in coronary arteries and saphenous vein grafts.

Directional coronary atherectomy (DCA) was performed in 158 patients over a 2-year period at the Mayo Clinic. Primary atheromatous lesions were treated in 92 patients (group 1) and restenosis lesions were treated in 66 (group 2). Technical success (recovery of tissue and greater than or equal to 40% luminal enlargement with a residual stenosis of less than 50%) was achieved in 152 lesions (92%); clinical success (technical success and no in-hospital death, Q-wave myocardial infarction or coronary bypass surgery) was achieved in 143 patients (91%). Adjunctive balloon angioplasty was used in 41 patients. DCA was successful less often in group 1 than in group 2 (86 vs 97%; p = 0.038). A major complication occurred in 7% of patients; in-hospital death, Q-wave myocardial infarction and emergency coronary bypass surgery occurred in 3, 1 and 4% of patients, respectively. Major complications were more frequent in group 1 than in group 2 (10 vs 1; p = 0.02). During a follow-up period of 14 +/- 8 months, no difference between the groups was found in the incidence of late death (4%), Q-wave myocardial infarction (1%), recurrent severe angina (29%), bypass surgery (15%) or repeat interventional procedure of the same vascular segment (24%). Vein graft and restenosis lesions tended to have greater success and fewer complications. Angiographic restenosis (increase of greater than or equal to 30% in stenosis severity by visual assessment) occurred in 62% of patients and 58% of lesions with successful DCA, and was similar in the 2 groups; a tendency toward higher restenosis rates was seen in patients with vein graft DCA.(ABSTRACT TRUNCATED AT 250 WORDS)


Relation of regression of left ventricular hypertrophy to changes in ambulatory blood pressure after long-term therapy with perindopril versus nifedipine.

Casual as well as ambulatory 24-hour blood pressure (BP) and echocardiographic parameters were studied in 40 patients with untreated or insufficiently treated mild to moderate essential hypertension. Left ventricular (LV) hypertrophy was assessed before and after 24 weeks of therapy with either the converting enzyme inhibitor perindopril or the calcium antagonist nifedipine. The design was a double-blind parallel study with a placebo run-in period. Patients received a daily oral dosage of either 4 to 8 mg of perindopril or 40 to 80 mg of nifedipine in slow-release form. A diuretic (25 mg/day of hydrochlorothiazide) was added in nonresponders (greater than 90 mm Hg casual diastolic BP). Once-daily perindopril and twice-daily nifedipine comparably reduced both casual and ambulatory BP throughout 24 hours (p less than 0.01) without affecting 24-hour heart rate. Six subjects withdrew from the nifedipine group and 4 from the perindopril group. After 12 and 24 weeks of therapy, LV hypertrophy was significantly reduced by both agents. Before active treatment was begun, LV mass index was more closely correlated to 24-hour (p less than 0.001) than to casual BP. This correlation disappeared after treatment with both agents. The correlation between ambulatory systolic day-time BP and LV mass was only still present (r = 0.54; p less than 0.05) after 24 weeks of treatment with nifedipine. It is concluded that regression of LV hypertrophy during converting enzyme inhibition or calcium antagonism may be partly independent of dosage and magnitude of 24-hour BP decrease.


Effectiveness of endopeptidase inhibition (candoxatril) in congestive heart failure.

Candoxatril is a novel, orally active inhibitor of neutral endopeptidase EC 3.4.24.11, the enzyme that degrades atrial natriuretic peptide (ANP). The acute and chronic (10 days treatment) hemodynamic and hormonal effects of candoxatril (150 mg twice daily) in 12 patients with moderately severe congestive heart failure were investigated in a randomized, placebo-controlled, double-blind study. On study day 1, candoxatril acutely increased plasma ANP levels, suppressed aldosterone and decreased right atrial and pulmonary capillary wedge pressures. After 10 days of treatment, basal ANP was increased and basal aldosterone was decreased. Body weight was reduced, most likely reflecting chronic natriuretic or diuretic effects, or both, and there was a trend toward increased cardiac index and reduced preload values. On study day 10, the acute effects of candoxatril were similar to those on day 1 (i.e., ANP was further increased, aldosterone was suppressed, and right and left ventricular filling pressures were decreased). Thus, candoxatril may offer a new and effective therapeutic approach in the treatment of heart failure.


Immunohistochemical study of T cell receptor gamma delta cells in chronic liver disease.

The distribution and phenotypic characterization of T cell receptor (TCR) gamma delta cells in human liver tissue was investigated immunohistochemically at light and electron microscopic levels. In chronic liver disease, there was a significant increase in the number of TCR gamma delta cells and in the percentage of TCR gamma delta cells to CD3+ cells in the portal areas and hepatic sinusoids. Hepatic TCR gamma delta cells were classified as small or large gamma delta cells. Large gamma delta cells were increased in chronic liver disease, whereas both small and large gamma delta cells were increased in the portal areas and hepatic sinusoids in liver cirrhosis. The increased TCR gamma delta cells were of the BB3+ (peripheral) type, indicating that TCR gamma delta cells in the liver were of the same lineage as those in the peripheral blood. In addition, the majority of the TCR gamma delta cells in the portal areas of liver cirrhosis patients were CD4- and CD8- (double negative). Immunoelectron microscopy showed that the large gamma delta cells were lymphoblastoid and contained multivesicles. The present study clearly demonstrated that there are two types of TCR gamma delta cells, and that these cells were significantly increased in the livers of patients with chronic liver disease. This suggests that they may be involved in regulation of the immune response and hepatocellular damage in chronic liver disease.


A recombination event that redefines the Huntington disease region.

We report both a recombination event that places the Huntington disease gene proximal to the marker D4S98 and an extended linkage-disequilibrium study that uses this marker and confirms the existence of disequilibrium between it and the HD locus. We also report the cloning of other sequences in the region around D4S98, including a new polymorphic marker R10 and conserved sequences that identify a gene in the region of interest.


Halothane and isoflurane effects on Ca2+ fluxes of isolated myocardial sarcoplasmic reticulum.

To elucidate better the differential myocardial depressant actions of halogenated volatile anesthetics, anesthetic-induced changes in Ca2+ accumulation, release, and Ca-ATPase (Ca2+ pump) activity of isolated canine cardiac sarcoplasmic reticulum (SR) vesicles were examined. An initial crude microsomal fraction of homogenized canine ventricle was subfractionated on a discontinuous sucrose gradient after Ca2+ loading in the presence of phosphate. Junctional SR (JSR) enriched with terminal cisternae was identified by its content of an electrophoretically verified approximately 450-kDa protein, the Ca(2+)-release channel (CaRC). When the CaRC of JSR was blocked by 1 microM ruthenium red (RR), the rate of Ca2+ uptake increased 47% as measured spectrophotometrically using the Ca-sensitive dye antipyrylazo III. A second fraction was identified as primarily longitudinal SR (LSR) based on its trace content of 450-kDa protein and 11% increase of Ca2+ uptake with RR. Halothane (0.75-2.5%) or isoflurane (2.5-4%) decreased net Ca2+ accumulation rate by either LSR or JSR, and the decrease in uptake rate of JSR was only partially reversed by addition of 1 microM RR (27% increase for isoflurane, 7% increase for halothane). Both halothane and isoflurane increased JSR ATP consumption as measured by a coupled-enzyme assay. 45Ca2+ efflux from passively loaded SR vesicles was then determined to verify that the decreased net uptake rate was due to enhanced Ca2+ efflux from vesicles. Both anesthetics increased passive Ca2+ efflux from SR vesicles in which the CaRC was blocked by 10 microM RR as well as those in which Ca2+ release via the CaRC was activated by 10 microM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional heredity protein S deficiency with arterial thrombosis.

Protein S is a vitamin K-dependent protein that functions as a regulatory protein to limit clotting. The authors present and discuss the case of a 37-year-old man with a type IIa protein S deficiency. The diagnosis and treatment of a protein S deficiency is also described.


Quantitation of T-cell receptor V beta chain expression on lymphocytes from blood, brain, and spinal fluid in patients with multiple sclerosis and other neurological diseases.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system in which large numbers of T cells enter the brain and cerebrospinal fluid (CSF). To determine whether these cells represent restricted populations, we studied expression of T-cell receptor V beta chains on paired samples from the central nervous system and blood of patients with MS or other neurological diseases (OND) using a quantitative polymerase chain reaction. The distribution of V beta chain expression in blood was skewed, with a significant preponderance of message from V beta genes 1 through 8 (p = 0.0001). Such skewing was not present in samples from the CSF and brain. Patterns of V beta gene expression were different among paired samples from spinal fluid and blood and were relatively heterogeneous. Blood and CSF samples from a patient with acute meningitis were studied on two separate occasions. The patterns of V beta expression changed over 72 hours in both the blood and the CSF. With one exception, no oligoclonal populations of T cells were observed nor were there disease-specific patterns of V beta gene expression in the blood or CSF. Samples from 2 MS brains and 1 OND brain expressed patterns of V beta genes that were different and less heterogeneous than those in paired blood. In addition, expression of V beta 12 was remarkably increased in the 2 MS brains, suggesting a selective recruitment or expansion of T cells expressing this gene. These data demonstrate that populations of T cells from blood, spinal fluid, and brain differ from one another and can fluctuate during periods of acute inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)


[Reproducibility of the measurement of humeral artery diameter, velocity of carotido-femoral pulse wave and digital pulse wave in normal subjects].

The aim of this study was to assess the intra-observer reproducibility at short and medium term of three non-invasive methods of arterial measurement: in the same day eight volunteers underwent five successive measurements of brachial artery diameter by two dimensional pulsed Doppler of the carotido-femoral pulse wave velocity by a piezoelectric transducer. The measurements were repeated three times at two weeks' interval. The short term (same day) and medium term (after several weeks) reproducibility of the first two methods of measurement was good: 4.69 +/- 2.37%/4.24 +/- 1.90% and 4.09 +/- 1.16%/5.02 +/- 1.71% respectively for brachial artery diameter and carotido-femoral pulse wave velocity. The reproducibility of the method of measuring digital pulse wave velocity was 10.64 +/- 3.50%/11.62 +/- 4.25%, confirming the greater variability of this parameter. Our results with these noninvasive techniques indicate that they may be used to study the arterial system and could be clinically useful in the surveillance of hypertensive patients.


[Atrial natriuretic factor and cardiac insufficiency].

The atrial natriuretic factor (ANF) is a vasodilating and natriuretic peptide. In experimental and human cardiac failure, plasma ANF concentrations are increased. The ANF is a good marker of functional and haemodynamic severity and of the prognosis of cardiac failure. In this syndrome, messenger RNA of ANF is expressed not only in the atria but also in the ventricles which also secrete the peptide. Attenuation of the natriuretic response is observed in cardiac failure. It may be related to an abnormality situated after the receptor and second messenger, cyclic GMP and/or the reduction of renal perfusion pressure which occurs in cardiac failure. The therapeutic perspectives of ANF in cardiac failure are limited by the necessity of continuous intravenous or parenteral administration. Inhibitors of the enzyme degrading the peptide, neutral endopeptidase, are under evaluation in clinical trials which are at a preliminary stage for the moment.


Laparoscopic cholecystectomy. The new 'gold standard'?

Laparoscopic cholecystectomy has rapidly been adopted by surgeons, but concerns remain about its safety, the management of common bile duct stones, and the means of appropriate training. Of 647 patients referred for cholecystectomy, preoperative endoscopic retrograde cholangiography was performed in 49 (7.6%), with 27 patients (4%) undergoing sphincterotomy and stone extraction. Traditional cholecystectomy was performed in 29 patients (4.5%). Laparoscopic cholecystectomy was attempted in 618 patients and completed successfully in 600 (97.1%). Surgical trainees functioned as the primary surgeon in 70% of cases. Technical complications occurred in three patients (0.5%), including one patient with a common bile duct laceration (0.2%). Major complications occurred in 10 patients (1.6%), with no perioperative mortality. Mean postoperative hospital stay was 1 day, with return to work or full activity a mean of 8 days after surgery. Two cases of retained common bile duct stones (0.3%) were identified. We now regard laparoscopic cholecystectomy as the "gold standard" therapy for management of symptomatic cholelithiasis.


Intraperitoneal carbon dioxide insufflation and cardiopulmonary functions. Laparoscopic cholecystectomy in pigs.

We studied the effects of laparoscopic cholecystectomy on respiratory and hemodynamic function in eight adult pigs. Minute ventilation was adjusted to normalize baseline arterial blood gases, then fixed throughout carbon dioxide insufflation. A metabolic measurement cart recorded total CO2 excretion, oxygen consumption, and minute ventilation. Carbon dioxide pneumoperitoneum was maintained at a constant pressure of 15 mm Hg as cholecystectomy was performed. After 1 hour of insufflation, CO2 excretion increased from 115 +/- 10 mL/min to 149 +/- 9 mL/min but O2 consumption remained unchanged. The PaCO2 increased from 35 +/- 2 mm Hg to 49 +/- 3 mm Hg and arterial pH fell from 7.47 +/- 0.02 to 7.35 +/- 0.03. Systemic and pulmonary hypertension occurred and stroke volume dropped from 35.5 +/- 3.5 mL to 28.6 +/- 2.2 mL with compensatory tachycardia. Right atrial pressure remained unchanged as inferior vena cava pressure increased to reflect the intraperitoneal pressure. We conclude that CO2 pneumoperitoneum resulted in significant transperitoneal CO2 absorption, with secondary hypercapnia and acidemia. The accumulation of CO2 was also associated with an increase in systemic and pulmonary arterial pressure. Heart rate increased to compensate for the decreased stroke volume to maintain cardiac output.


Management of infrainguinal occluded vein bypasses with a combined approach of thrombolysis and surveillance. A prospective study.

Intra-arterial thrombolysis with urokinase was attempted on 23 occluded infrainguinal vein bypasses. Lesions revealed by thrombolysis included 11 anastomotic stenoses, five midbypass stenoses, five native artery stenoses, and five unusable diffusely stenotic vein conduits. Adjunctive procedures performed immediately after successful thrombolysis included 10 local surgical revisions, five balloon angioplasties, and five new vein bypasses. Three nonanastomotic vein bypass stenoses and two common iliac artery stenoses were detected using a surveillance protocol in subsequent follow-up of patients with patent bypasses. Twelve-month patency following thrombolysis (including immediate failures) was 52.4%. The use of thrombolysis in the management of occluded vein bypasses allows the identification and correction of pathological lesions. Once revised, continued vein bypass patency may be improved with a surveillance program.


Laparoscopic pelvic lymph node dissection for carcinoma of the prostate and bladder.

Improvements in instruments and camera systems have allowed the development of operative techniques for laparoscopic pelvic lymph node dissection. A series of dissections in 20 patients is reported. The mean operation time was 1 h and 40 min. When the nodes appeared malignant, a node biopsy was sent for frozen section. If this was positive, the dissection went no further. In three patients it was necessary to complete the operation by open surgery. A mean number of five lymph nodes was dissected per side. After laparoscopic dissection, all patients were discharged the morning after surgery. The operation is possible without making great demands on hospital bed occupancy and the patient has a comfortable and speedy return to normal activity. Using laparoscopic techniques, node dissection becomes a more appealing option as an investigation and staging procedure.