Exogenous but not endogenous PGE2 modulates pony tracheal smooth muscle contractions. The modulatory role of prostaglandin E2 (PGE2) was examined in pony tracheal smooth muscle strips. Although exogenous PGE2 inhibited the contractile response to both electrical field stimulation (EFS) and acetylcholine (ACh) in a dose-dependent manner, the concentration required to inhibit the response to EFS (10 nM) was less than that required to inhibit the response to ACh (0.1 microM). Cyclooxygenase inhibition with aspirin or meclofenamate had no effect on either the response to EFS or to ACh even though PGE2 production was inhibited. Our results demonstrate that in ponies as in other species, exogenous PGE2 can inhibit the airway smooth muscle's response to EFS and ACh. However, the failure of cyclooxygenase inhibition to alter the response to EFS and ACh suggests that endogenous prostanoids do not exert a significant modulatory effect on pony tracheal smooth muscle in vitro.


The inhibitory effect of furosemide on the contractile response of equine trachealis to cholinergic nerve stimulation. The effects of furosemide on the responses of equine trachealis muscle with and without epithelium to electrical field stimulation (EFS) and exogenous acetylcholine (ACh) were investigated in organ baths. Tissues were pretreated with guanethidine and the parameters used for EFS were those previously demonstrated to activate postganglionic cholinergic neurons. In tissues with intact epithelium, furosemide (100 microM) shifted the frequency-response curve to the right. In the preparations without epithelium, furosemide did not affect the response to EFS. Neither in epithelium-on nor in epithelium-off tissues was the ACh dose-response curve affected by the administration of furosemide. We conclude that furosemide (100 microM) decreases the equine tracheal smooth muscle responses to EFS through inhibition of cholinergic neurotransmission, and that this effect is dependent on epithelium.


Atypical presynaptic alpha-adrenoceptor modulation of neurally-mediated cholinergic responses in guinea-pig tracheal smooth muscle. Cholinergic excitatory nerves in guinea-pig trachea are subject to inhibitory control by presynaptic alpha 2-adrenoceptors. Recently, the nature of these receptors has come into question insofar as the presynaptic inhibitory effects of the alpha 2-adrenoceptor agonist, clonidine, in the guinea-pig trachea have been shown to be antagonized by the alpha 2-adrenoceptor antagonist, yohimbine, as well as the alpha 1-adrenoceptor antagonist, prazosin. This inhibitory action of prazosin had not been described previously in the airways and may relate to the use of norepinephrine rather than clonidine as the alpha-adrenoceptor agonist in earlier studies. The present study evaluates the susceptibility of norepinephrine-induced inhibition of neurally-mediated cholinergic excitatory responses to antagonism by prazosin and yohimbine under conditions identical to those which showed clonidine to be sensitive to these antagonists. In tissues pretreated with guanethidine, propranolol and indomethacin, norepinephrine (1 microM) induced a 37-fold rightward shift of the frequency-response curve for neurally-mediated cholinergic contractions which was reversed partially by pretreatment of tissues with yohimbine. Norepinephrine also caused a concentration-dependent inhibition of cholinergic 'twitch' responses induced by intermittent (1 Hz) nerve stimulation. This action of norepinephrine was antagonized in a concentration-dependent manner by yohimbine but was unaffected by prazosin. These results indicate that in guinea-pig trachea the presynaptic inhibitory actions of norepinephrine on cholinergic nerves are mediated via classical alpha 2-adrenoceptors, i.e. receptors that can be blocked by yohimbine but not by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)


A novel method to assess airway function parameters in chronically instrumented, unrestrained guinea-pigs. A new method has been developed to measure airway functions in unanaesthetized, unrestrained guinea-pigs. The technique utilizes a specially designed pneumotachograph that is placed inside the trachea, and a saline-filled balloon, placed inside the pleural cavity. The pneumotachograph consists of a stainless steel cylinder with coaxial and perpendicular tubes attached to it, measuring the total pressure and the lateral pressure in the trachea, respectively. Via air-filled silicon conducting tubes, subcutaneously driven and permanently attached to the neck of the animal, the pressures are fed into a differential pressure transducer, yielding a pressure difference proportional to the airflow in the trachea. Via a saline-filled tubing, the pleural balloon is similarly attached to the neck of the animal, and pleural pressure (Ppl) is measured using a second pressure transducer. These data permit calculation of airway functions in conscious, unstressed animals. Control values for airway resistance (RAW), Ppl, tidal volume and respiratory frequency are all in the range of results reported previously for this species. A very significant correlation between RAW and Ppl (P < 0.001) was observed, indicating that sole Ppl-measurement can be used as a relatively simple and sensitive method to assess bronchial obstructive reactions in unrestrained guinea-pigs. Using a specially designed provocation cage, which allowed the animals to remain in a stress-free, unrestrained condition, the method has been successfully applied for the assessment of the dose-dependent bronchoconstrictor sensitivity to histamine as well as to allergen-induced early and late phase airway reactions.(ABSTRACT TRUNCATED AT 250 WORDS)


Gas exchange and regional redistribution of pulmonary blood flow during resuscitation of acute pulmonary bead embolization. Acute pulmonary embolism (PE) was induced by injecting polystyrene beads into the right atrium of 18 anaesthetized dogs. The animals were resuscitated for 45 min with either Ringer's Lactate (RL), norepinephrine (NE) or isoproterenol (IP). The multiple inert gas elimination technique (MIGET) was used to estimate the distributions of ventilation (V) and blood flow (Q) to different V/Q regions. Measurements were made prior to embolism, 10 min after PE and during the resuscitative phase. Microspheres with three different radioactive labels were also used to mark blood flow distribution to different lung regions in these three phases. The data show that cardiac output decreases after PE, while perfusion to shunt and low V/Q regions increases. Pulmonary blood flow heterogeneity, estimated from the MIGET data, is also increased after PE. Resuscitation by RL or NE consistently increases cardiac output but IP does so inconsistently and is associated with systemic hypotension. All three methods of resuscitation cause increases in perfusion to the shunt and low V/Q regions but no change in perfusion heterogeneity in the remaining V/Q units. Increases in regional blood flow during resuscitation occur preferentially in the less embolized areas. The concomitant increase in perfusion to shunt and low V/Q units suggests that increased perfusion to these less embolized regions results in further hypoxemia despite improvement in cardiac output.


The administration of psychotropic and anticonvulsant drugs to children with profound intellectual disability and multiple impairments. A national (England and Wales) postal survey of families with a son or daughter with profound intellectual disability and multiple physical and sensory impairments who lived at home was undertaken. A section of the questionnaire dealt with prescription of major tranquillizers, drugs with a sedative function, anticonvulsants and stimulants, while among other variables information was also collected on sex, age, behaviour problems, sleep difficulties and epilepsy. Of children and adults: 5.3 and 7.9%, respectively, were receiving major tranquillizers; 28.5 and 24.5%, respectively, were prescribed drugs with a sedative function; and 53.4 and 52.7% were in receipt of anticonvulsants, with no individuals in receipt of stimulants. Only 1.5% of the total sample received major tranquillizers, drugs with a sedative function and anticonvulsants, though 18.9% were prescribed drugs from two classes, notably drugs with a sedative function and anticonvulsants. In all, 66.3% of the combined child and adult samples received at least one drug from the classes investigated. No sex bias in prescribing was found. Receipt of major tranquillizers bore some relation to reported behaviour problems, while administration of sedatives and anticonvulsants were related respectively to reports of sleep problems and occurrence of epilepsy.


Activities and engagement in day services for people with a mental handicap. Policy on the role and function of day services for adults with mental handicaps has changed considerably during the last 2 decades. What such settings offer their users has also changed as services have attempted to evolve in line with policy. However, the impact of these changes has gone largely unevaluated. This paper describes a study of two day centres to categorize the activity programmes of these services, and to assess service user and staff behaviour prior to a larger scale study of such services in Wales. The two centres were found to differ significantly in their programmes but not in the extent to which activities were organized in the community. Service user participation in activities varied with activity type, group composition and activity location. Whether activities were organized for the full duration of the timetabled sessions was critical to the interpretation of the extent of service user engagement. Staff showed a commendable orientation to clients and their activities in both services. Differences in the activity programmes of the two centres are discussed in terms of a continuing lack of clarity over the purposes of such day services in general. The relevance of some activities to objectives is questioned. Concern is also expressed about the resulting level of engagement achieved in planned activity.


Prediction of the number of Down's syndrome infants to be born in England and Wales up to the year 2000 and their likely survival rates. Using current demographic projection of maternal age-structure, age-specific fertility rates, and the availability, detection and utilization rates of prenatal diagnosis and subsequent termination rates, predictions are made of the likely numbers of births with Down's syndrome (DS) in England and Wales to be expected up to the year 2000. Further predictions are made of age-specific prevalence of the condition bearing in mind recent trends in survival. These figures show that, despite current screening policies based on maternal age alone, the observed live birth prevalence of DS will rise to levels higher than have been seen for 20 years. Together with consistently increased survival, this will mean that, throughout the next century, the population prevalence of DS will be higher than ever before. Work based in other countries has reached similar conclusions. As the prevention of all births affected by DS is not possible in the forseeable future, and some would argue that it is not desirable, society will need to provide for those affected.


Appraised significance of intellectual disability for parents of children in three age cohorts: exploring the stress process. The conceptualization of stress as a process involving stressors, mediators and manifestations of stress has opened up a way of more systematically investigating the impact of perceptions on stress experienced by parents of children with intellectual disabilities. Results obtained at the end of the first part of a two-stage panel design study indicate that appraised significance perceptions of parents are potentially exacerbating mediators of parental stress. Findings of a multiple regression analysis were interpreted as being consistent with the proposition that the parent-appraised significance of the child's disability for their parental role becomes increasingly salient as an exacerbating mediator of parental stress during the later childhood to early adolescent years. An attempt will be made to test this proposition when the children in the 3-5 year old cohort moves into the 10-12 year-old age category.


Increases in knowledge following a course of sex education for people with intellectual disabilities. Although sex education programmes are thought to be useful in teaching people with intellectual disabilities, there is very little evidence that the material taught is retained by clients. This paper reports data which has been collected routinely on a sex education programme. Forty-six subjects were assessed on their level of sexual knowledge in seven areas: parts of the body, masturbation, male puberty, female puberty, intercourse, pregnancy and childbirth, and birth control and venereal disease. They were retested after a 9-month sex education programme and tested again at a 3-month follow-up. A control group of 14 subjects were tested on two occasions, 4 months apart. There were significant and substantial increases in sexual knowledge on all areas for the experimental group. The control group showed no corresponding increases in knowledge.


A double-blind comparison of zuclopenthixol tablets with placebo in the treatment of mentally handicapped in-patients with associated behavioural disorders. Fifty-two mentally-handicapped in-patients with associated behavioural disorders were entered into this double-blind trial comparing zuclopenthixol dihydrochloride tablets (10 mg) with placebo. The study consisted of a 6-week open phase, in which all patients were treated with zuclopenthixol tablets, followed by a 12-week double-blind phase where approximately half of the patients were transferred to placebo tablets. Demographic data was obtained from the patients at entry to the study. Clinical assessments were performed at weeks 6, 7, 8, 10, 14 and 18 using the Clinical Global Assessment (CGA), a Behavioural Disorder Assessment prepared specially for this study, and a side-effect check list. Analyses of the rating scales showed significant differences in favour of zuclopenthixol at end-point on the item 'improvement in behaviour disorder' from the CGA and at week 14 and end-point on the Assessment of Behavioural Disorder. All other results demonstrated a favourable trend towards the zuclopenthixol treatment. Side-effects were reported slightly more frequently in the zuclopenthixol group, but generally, they were not a problem.


Behavioural continence training in mental handicap: a 10-year follow-up study. Ten years after continence training, 14 severely and profoundly mentally handicapped individuals were found to have substantially maintained their improvements in bladder control. Completely independent self-initiated toileting had not been maintained, but the level of prompting to toilet was considerably less than before training. Those who had received intensive individual training fared much better than those who had received less intensive group training. Intensive individual training was found to be cost effective and resulted in very substantial savings in career time.


A psychodynamic approach to emotional difficulties within a social framework. Emotional difficulties and their relationship to challenging behaviour are recognized and treated in a normal environment, providing a measurable reduction in maladaptive and anti-social behaviour. The implications for community care are highlighted.


[Analysis of the treatment with traditional Chinese medicine in chronic glomerulonephritis based on histopathologic type]. The histopathologic type of 189 cases of chronic glomerulonephritis (GN) were confirmed by renal biopsies, they were subdivided into 3 groups. 77 patients of Western medicine (WM) group was treated by conventional WM (prednison or CTX), and after treatment the total effective rate was 55.8%. The TCM-WM group was treated by the same WM plus treatment according to Syndrome Differentiation with Chinese medicinal herbs, and the total effective rate was 86% in 50 patients. The TCM group was treated by Chinese medicinal herbs, and the total effective rate was 67.3% in 62 cases. There was very significant difference (P < 0.01) between the WM and the TCM-WM group. Among the patients of TCM-WM and TCM groups, 67% of 112 cases were manifested as Dampness-Heat Syndrome, so it suggested that one of the important method for GN treatment is clearing away Dampness-Heat. The effects of TCM-WM group is much better than the WM group in treating mesangio-proliferative GN and membranous GN. It was difficult for WM in treating IgA nephropathy, membrano-proliferative GN and focal glomerulosclerosis, but Chinese medicinal herbs were effective with replenishing Qi and strengthening the Spleen, clearing away Dampness-Heat, promoting blood circulation and relieving Stasis, etc.


[Pathogenic factor (Dampness-heat) of glomerulopathy]. Mesangial proliferative glomerulonephritis (MsPGN) induced by chronic serum sickness in rabbits coincide with the human chronic progressive glomerulonephritis resulted from repeated infection, which is similar to pathologic changes of Dampness-Heat Syndrome. The experimental model of MsPGN was treated by Abelmoschus manihot. which could remove the Dampness-Heat. The amount of proteinuria in treating and control group were 62.68mg/24hr and 121.94mg/24hr respectively (P < 0.05), the number of cells in glomeruli were 61.54 and 80.39 respectively (P < 0.01), and diameters of glomeruli were 102.43 microns and 121.13 microns respectively (P < 0.01). It suggested that the drug could alleviate circulating immune complex (CIC) mediated renal injury.


Long-term cultures of mouse bone marrow cells: a model for studying the generation of natural killer cells. We investigated the generation of natural killer (NK) cells, using a long-term bone marrow culture (LTBMC) system. Mouse bone marrow cells were cultured for 2 weeks in complete medium without growth factors to obtain an enriched population of NK precursor cells. When these cells were recultured in the presence of interleukin-2 (IL-2) and conditioned medium (CM) from LTBMC, lytic NK cells were generated within 4 days. Replacing CM with fresh medium, before adding IL-2, decreased NK cell generation markedly, suggesting that endogenous factors present in CM were necessary for IL-2 induction of NK cells. NK cell precursors were also cultured with a combination of IL-2 and interferon-gamma (IFN-gamma) or IL-2 and tumor necrosis factor-alpha (TNF-alpha), but no CM. Results show that IFN-gamma and TNF-alpha were able to substitute CM. The addition of anti-IFN-gamma or anti-TNF-alpha antibodies to LTBMC cells, cultured in the presence of IL-2 and CM, inhibited cytotoxicity induction in a dose-dependent manner. The data indicate that IFN-gamma and TNF-alpha production may be required for IL-2 induction of NK activity, and are consistent with the hypothesis that NK generation involves collaboration between IL-2 and other bone marrow microenvironmental growth factors.


[Effect of baoyuantang on erythroid progenitor and clinical observation in chronic renal failure patients]. The erythroid colony formating ability and the therapeutic efficacy were investigated in patients with chronic renal failure (CRF) before and after treatment with baoyuantang. The results showed that the number of CFU-E, BFU-E of bone marrow was found lower in CRF patients than that in normal controls, and there was inhibitory action in the CRF serum on the number of CFU-E, BFU-E of normal human bone marrow. After treatment with baoyuantang, the amount of Hb was increased and creatinine decreased in CRF patients, and its effective rate reached 83.3%. The above-mentioned inhibitory action in CRF serum was also reduced post-treatment. The results indicated that baoyuantang could increase the ability for proliferation and differentiation of erythroid progenitor and adjust anemia in CRF patient.


[Treatment of 100 children with infantile nephrotic syndrome by integrated traditional Chinese medicine and Western medicine]. For ten years (1979-1989), 150 cases of infantile nephrotic syndrome were treated by integrated TCM and Western medicine (WM). The WM group (50 cases) was treated by conventional WM drugs (prednisone, CLB, etc) and the TCM-WM group (100 cases) was treated by the above-mentioned WM plus treatment according to Syndrome Differentiation with decoction of Chinese medicinal herbs. Wulin San, Zhenwu Tang and Zhibai Dihuang Tang were selected in treating Spleen-Qi Deficiency distressed by Dampness, both Spleen-Kidney Yang Deficiency and both Liver-Kidney Yin Deficiency Syndrome respectively. The total effective rate was 100%, and the efficacy of TCM-WM group was higher than that of WM group (P < 0.005). The efficacy of TCM-WM treatment of nephritic nephropathy was far better than that of simple nephropathy (P < 0.05). Also the efficacy of TCM-WM was superior in raising plasma albumin and reducing blood cholesterol than that of WM (P < 0.001). The cellular immunity function and plasma cortisol of TCM-WM group were significantly improved than that of WM, P < 0.01 and 0.001 respectively. The result showed that the curative effect of the TCM-WM group in treating nephrotic syndrome was much better than that of WM alone.


Non-lytic pre-NK cells are enriched in the spleen as a result of long-term depletion of mature NK cells with anti-NK-1.1 monoclonal antibody. In this study, we wanted to establish a new model as an alternative to bone marrow, where non-lytic pre-NK cells can be further studied with respect to phenotype and relation to other haematopoietic cell lineages. B6 mice were depleted of mature NK cells by either weekly injections from birth, or a single injection as adults, with the monoclonal antibody anti NK-1.1, and the frequency of interleukin-2 (IL-2)-responding cells (as determined by cytotoxicity or proliferation) was investigated. By comparing the frequency of IL-2-induced cytotoxic cells between NK-1.1(-) mice depleted from NK cells by a single injection with those depleted from birth, we observed a 3-fold higher frequency in mice depleted from birth [1/(11,941 +/- 30) vs. 1/(29,903 +/- 104)]. Non-lytic pre-NK cells were further enriched by selective in vitro depletion of sIg+, CD4+ and CD8+ cells. In this non-B, non-T spleen cell population the frequency of cells proliferating in response to 7 days culture with IL-2 or IL-3 was 2-fold higher in NK-1.1(-) mice than in control mice [1/(4,340 +/- 27) vs. 1/(9,250 +/- 67) and 1/(3,370 +/- 41) vs. 1/(7,610 +/- 50), respectively]. We conclude that NK depletion from birth results in an enhanced frequency of pre-NK cells, and propose this as a model to further study the identity of the progenitor and pre-NK cell.


Enhanced splenic bacterial clearance and neutrophilia in anti-NK1.1-treated mice infected with Pseudomonas aeruginosa. The purpose of the present study was to further delineate the role of natural killer (NK) cells in the early stages of resistance to infection by Pseudomonas aeruginosa, strain PAO1. Intravenous injection of the monoclonal antibody alpha-NK1.1 resulted in an 82% reduction in NK cell activity of normal mice, as measured by a standard 4-hour 51Cr release assay. Splenic bacterial clearance was examined in mice treated with this antibody 12 h prior to infection with a sublethal dose (10(6)) of PAO1. At 2, 4, and 6 h postinfection there was significant enhancement (up to 10-fold) of clearance in mice treated with alpha-NK1.1 when compared to untreated infected control animals. Interestingly, the enhanced clearance of PAO1 in the spleens of NK-depleted mice was found to be coupled to a significant increase in neutrophils. Normal murine spleens were found to contain 1-2% neutrophils, which increased to 6-7% following sublethal infection. However, in mice treated with alpha-NK1.1 and infected, splenic neutrophils increased up to 15% during the early stages of infection. The data presented here suggests that NK cells do not have direct bactericidal activity against Pseudomonas, but may regulate other effector cells, such as neutrophils-an indirect role for natural killer cells, probably mediated in vivo by their production and secretion of cytokines.


Effect of human transferrin on the engraftment of allogeneic bone marrow in various strans of lethally irradiated mice. The effect of human iron-saturated transferrin (siderophilin) on the engraftment of H-2-incompatible bone marrow and on the induction of durable allogeneic, hemopoietic chimerism was investigated in BALB/c mice grafted with bone marrow from C57BL/6 donors, and in C57BL/6 mice grafted with bone marrow from C3H/He donors. Administration of transferrin to mice after irradiation and marrow transplantation resulted in considerable protection, yielding permanent allogeneic chimerism in BALB/c mice. No effect was observed in the C57BL/6 mice in which transplantation of bone marrow from C3H/He donors provided a high survival rate even without any further treatment. Serum levels of transferrin were remarkably constant in these mice and no significant differences were seen in the circadian cycle, after lethal irradiation and at different times after marrow transfer. A modest rise of transferrin occurred only in the course of chronic graft-versus-host disease. It thus seems that the promoting effects of transferrin [Pierpaoli et al: Cell Immunol 1991; 134:225-234] depend on the murine, histoincompatible H-2 combination utilized and is not attributable to quantitative changes of transferrin levels after marrow transplantation. The utilization of more specific activity of the transferrin is thus feasible.


[Clinical and experimental studies of royal made ping an dan on treatment of motion sickness]. This paper presents the results of clinical observation and experimental research of Royal Made Ping An Dan (RPAD) of the Imperial Hospital of Qing Dynasty. The clinical results showed that RPAD was effective in treating 343 patients with motion sickness, and their average time for producing effect was 24.1 +/- 13.5 minutes. The total effective rates of dramamine group and Ren Dan group were 69.4% and 67.7% respectively, the latter included 45.7% of basically cured and 55.0% of markedly effective cases. There were significant differences among these groups (P < 0.05-0.01). It revealed that the effect of RPAD was better than that of dramamine and Ren Dan. According to laboratory findings, RPAD had the ability of alleviating symptoms of motion sickness and inhibiting eyeball tremor and improving meningeal microcirculation of experimental animals.


[Preliminary report of the treatment of luteal phase defect by replenishing kidney. An analysis of 53 cases]. 53 patients with Luteal phase defect (LPD) were treated with different Chinese medicinal herbs at different phases of menstrual cycle. On the 5th day of the menstrual cycle, the treatment was implemented with the rationale of "nourishing the Kidney Yin, invigorating the Spleen and replenishing the Qi, promoting the blood circulation and enriching the Blood" which might promote follicular development. The principle for the postovulatory treatment was that "invigorating the Kidney and strengthening the Yang" might enhance the development of corpus luteum and maintain its function. The patients were treated for three menstrual cycles. There were significant improvement in the luteal phase of endometrium, and prolonged basal body temperature elevation in progestational stage with a tendency for normalization of the wave forms and its amplitude after the treatment. In the mid-progestational stage, the level of serum LH and PRL were reduced (P < 0.05) and that of serum progestin (P) rose significantly (P < 0.01), as compared with those before the treatment. The findings suggested that Chinese herbal medicines capable of replenishing the Kidney could regulate the hypothalamus-pituitary-ovarian axis and thus improve the luteal function. Among the 53 cases, 22 (41.5%) conceived but 68.18% of them required other measures to preserve the pregnancy.


[Therapeutic changes in nephrotic syndrome treated with yiqi huoxue jiedu decoction and corticosteroid]. Plasmic and urinary TXB2 and 6-Keto-PGF1 alpha of 87 patients of nephrotic syndrome (NS) and 25 healthy subjects were measured by RIA, and the influence of Yiqi Huoxue Jiedu decoction (YHJ) and corticosteroid on above-mentioned parameters was investigated. Plasmic and urinary TXB2 as well as the ratio of TXB2/6-K-PGF1 alpha of both types of NS increased (P < 0.01-0.05). The plasmic TXB2 of II type was higher than that of I type of NS (P < 0.01), 6-K-PGF1 alpha increased as well (P < 0.05). After treatment, plasmic and urinary TXB2 of both types of NS were remarkably lower (P < 0.01), while urinary 6-K-PGF1 alpha increased significantly (P < 0.05). In comparing with pre-treatment investigation, the plasmic 6-K-PGF1 alpha of II type was reduced (P < 0.05). It was shown that YHJ would inhibit the synthesis of TXA2 and regulate the TXA2-PGI2 balance. YHJ was markedly effective in producing TXB2 and 6-K-PGF1 alpha increase, its therapeutical effects was better to patients with Yin Deficiency and both Qi-Yin Deficiency, but not so well with Yang Deficiency Syndrome.


[Abnormality of T lymphocyte subsets in aged persons with kidney deficiency syndrome and its influence on immunologic regulation]. T lymphocyte subsets were investigated in 57 aged persons with Kidney Deficiency Syndrome as well as in 30 normal controls with application of the monoclonal antibody (OKT3, OKT4, OKT8). The results showed that the percentage of OKT3, OKT4 in the aged persons was significantly lower than that of control (P < 0.01), while OKT8 was significantly higher (P < 0.01). The OKT4/OKT8 ratio was significantly lower than that of control (P < 0.01). However, the above-mentioned changes were more evident in the Kidney Yang Deficiency Syndrome than those in Kidney Yin Deficiency Syndrome (P < 0.01). The further analysis indicated that the aged persons with Kidney Yang Deficiency appeared as marked positive correlation (r = 0.64, P < 0.001) between the OKT4/OKT8 ratio and IgA, and they also appeared as marked negative correlation (r = -0.89, P < 0.001 and r = -0.665, P < 0.001 respectively) between the OKT4/OKT8 ratio and C3 or CIC. The results suggested that the imbalance of the cell mediated immunity expressed by the T lymphocyte subsets in aged persons with Kidney Deficiency might be one of the essences of senility.


[Immunohistochemical study on the enteroendocrine cells of the small intestine in experimental spleen deficiency syndrome in rats]. 50 adult Wistar male rats were used and divided into 4 groups, i.e. normal control group, experimental Spleen Deficiency group induced by rhubarb, spontaneous recovery group and therapeutic group treated with Chinese recipe (Si Jun Zi decoction). All the animals of the 4 groups were killed simultaneously, and the jejunum and ileum were removed and processed for demonstration of gastrin cells and 5-HT cells according to immunohistochemical PAP technique. In addition, HE stained samples were prepared. The immunoreactivities of the two types of enteroendocrine cells were observed and semiquantitative estimation were performed under light microscopy. In addition, the immunoreactivities of 5-HT cells in normal control and experimental Spleen Deficiency group were measured by microspectrocytophotometer (MPV 2, Leitz). All the data were treated statistically. This study revealed that there were no obvious histological changes in the mucosa among the 4 groups. In the jejunum, the percentage of gastrin cells(+) in experimental Spleen Deficiency group was more than that of the normal control group, while the percentage of gastrin cells( ) was less than that of the normal control group. As compared with spontaneous recovery group, it showed contrary to the above result in the therapeutic group. No gastrin cells were found in the ileum in all the 4 groups. the percentage of 5-HT cells did not show significant changes in the jejunum and ileum among the 4 groups. But immuno-reactivity in the 5-HT cell was less than that of the normal control group in the jejunum of the Spleen Deficiency group.(ABSTRACT TRUNCATED AT 250 WORDS)


Long term tumorigenicity of a single application of indomethacin or Amuno in adolescent and in adult male Sprague Dawley rats. 200 adolescent (Group I) and 200 adult male Sprague Dawley rats (Group II) were divided into 4 subgroups of 50 animals each. Animals were treated on the 29th (Group I) or 98th day of life (Group II) either with acetone or Amuno carrier in acetone or Amuno on acetone (2.5 mg indomethacin/100 g animal weight in acetone) or with the pure substance indomethacin 2.5 mg/100 g of animal weight in acetone, giving a single application on the shaved dorsal skin. Subsequently the animals remained under observation until their deaths, followed by autopsy and histopathologic examination of several organs. The rats treated with Amuno of indomethacin in the adolescent stage showed lower body weights and a shorter total survival time. The adolescent animals treated with Amuno or indomethacin showed a significantly higher rate of interstitial testicular tumors of the Leydig tumor type, adenomas and adenocarcinomas of the small and large intestine as well as hepatocellular tumors. The total number of neoplasias was higher in the animals treated with Amuno or indomethacin compared to those treated with acetone or carrier with acetone. Application of Amuno or indomethacin also resulted in a higher rate of hyperplasias (sole of foot, lymph nodes, prostate). The impairment of the synthesis of prostaglandins caused by indomethacin apparently results in starting complex pathomechanisms which have effects until the late death of the animals. Adolescent animals were affected more frequently by the application of indomethacin as were already adult animals.


Delayed fetal development in two models of disturbed pregnancy of rats. Effect on mortality, body mass development, blood urea nitrogen (BUN) and urinary ammonium concentrations during the first week of extrauterine life. To induce pregnancy disturbance, two models were used ("endotoxin-model" and "stress-model"), both causing decreased fetal body mass. Fetuses were delivered by Caesarean section in the morning of the 21st gestational day. Postnatal mortality rate during rearing for one week amounted to 12% in controls and was enhanced in the endotoxin- and stress-models (to approximately 25% and approximately 30%, respectively). During this period body mass gain of surviving pups was significantly delayed in the stress-model (approximately 140% of birth mass), compared with controls or pups of the endotoxin-model (160% and 155%, respectively). Additionally, decreased BUN concentrations were registered in newborns as well as 7-day-old pups of the stress-model. Urinary ammonium concentrations were not changed significantly. Possible alterations of metabolic processes in pups of the stress-model are discussed.


[In vivo and in vitro biocompatibility tests of endodontic cements]. The major goal endodontic therapy has been achieved by condensing filling materials into the root canal. It's not uncommon to find excess material into the periapical tissue. It therefore becomes obligatory to use fillings materials that have acceptable biocompatibility. The purpose of this investigation was to obtain a "toxicity profile" of some endodontics materials and to compare our observations to results present in literature. The gutta-percha and five endodontic filling cements were tested "in vivo" and "in vitro". The in vivo biocompatibility involved the placement of the test material in 10 mm. Teflon tubes with an outer diameter of 1.3 mm which were implanted subcutaneously into rats. The implants were left in situ for periods of 30 and 90 days. The "hemolysis test" is designed for "in vitro" evaluations. The histological examination showed different intensity and extent cellular responses. In some cases severe infiltration of inflammatory cell and areas with necrotic were seen. At conclusion, the endodontics material evaluated showed slight, moderate and severe reactions; therefore a different pattern in tissue response.


Metastatic capacity of Burkitt's lymphoma cell lines in nude mice. Burkitt's lymphoma (BL) cell lines estimated in a previous study as having a high, low and no tumourigenicity (7) were intravenously (i.v.) injected into preirradiated (480 rad) nude mice. BL cell lines with a high tumourigenic potential produced metastatic tumours in the brain, spinal cord, bone marrow, stomach and kidney, but did not disseminate into the lung, liver, ovary and spleen. The survival time of the tumour bearing animals ranged from 2 to 10 weeks. The majority of mice i.v. injected with highly tumourigenic BL cell lines showed paresis or paralysis of the hind legs. This was associated with the presence of neoplastic nodules either in the brain and/or in the spinal cord. In animals with metastasis to the stomach and kidney progressive cachexia was observed. The described experimental model of metastatic BL tumours in nude mice can effectively be used for the in vivo study of new therapeutic molecules such as monoclonal antibodies coupled or not to substances, toxic to tumour cells. This model can also be useful for the identification and analysis of homing properties of BL cells and their implication in BL pathogenesis.


Frequency of spontaneous tumors in Wistar rats in 30-months studies. Tumors occurring in 450 male and 450 female control rats of the strain Wistar (BOR:WISW (SPF Cpb), breeder: Winkelmann, Borchen) employed in 9 control groups from 7 different 30-month studies were compiled on the basis of histopathology reports. 445 male and 448 female rats were evaluated. The remaining animals were unavailable due to autolysis. A total of 1211 tumors (565 in males, 646 in females) were seen in 716 rats (333 males, 383 females), 251 of which were classified as malignant (100 in males, 151 in females). About 44% of all primary tumors were located in the pituitary and adrenals alone. Average frequencies of primary tumors: pituitary 35.4%, uterus 34.0%, adrenals 26.5%, testes 15.8%, thyroid gland 11.8%, mammary glands 11.4% and 22.5% in females respectively, skin/subcutis 6.3%, ovaries 2.9%, endocrine pancreas 2.5%, hemolymphoreticular system 2.3%, liver 1.9%, heart 1.7% and various other organs showing tumor frequencies of less than 1.5%. Male animals exhibited strikingly more tumors of the adrenals, skin, endocrine pancreas, heart and brain, while pituitary tumors were predominant in females. A comparison of these data with those from 24-month studies in Wistar rats from the same breeder shows a considerable increase above all in the number of primary tumors, the number of tumor bearers as well as the number of tumors in the pituitary, adrenals, testes, mammary glands and heart. An extension of carcinogenicity studies to 30 months probably makes it harder to recognise tumorigenic effects of test substances, at least in some organs, than in two-year studies because of the high and variable spontaneous tumor rates.


Morphological effects produced, in vitro, by ferric oxalate treatment of enamel surfaces. A preliminary SEM study. The morphological changes produced, in vitro, by application of ferric oxalate on enamel surfaces were examined by scanning electron microscopy. Exposure of human enamel surfaces to ferric oxalate (5.3% w/w aqueous solution or added to phosphoric or citric acid) resulted in cleaned, activated enamel surfaces and a mild etching which increased surface roughness and porosity. Deposition of crystal formations occurred in approximately 50% of the examined areas. Crystals bond firmly to the porous underlying surfaces and resist washing with 5, 10 or 20 ml of distilled water.


Tissue oxygen pressure (ptO2) in extracellular volume expansion and hypervolemic polyglobulia. Muscle tissue oxygen pressure (ptO2) was measured in rats employing the microwire platin electrode according to Kessler and Lübbers. In extracellular volume expansion up to 50% above the normal volume the ptO2 histograms are situated within the normal range. Increase of the interstitial space for oxygen diffusion seems to be effectively counterbalanced by increased cardiac output. In hypervolemic polyglobulia, hematocrit about 60%, four rats presented normal ptO2 levels. In one animal only the ptO2 histogram was shifted to the left (lower values); in this rat also cardiac output was considerably reduced.


Influence of bile acids on stimulated lipid peroxidation and hydrogen peroxide production in rat liver microsomes. Bile acids were found to be effective antioxidants in bile and intestine. The influence of different bile acids on the NADPH-Fe(++)-stimulated lipid peroxidation (LPO) and cytochrome P-450 dependent hydrogen peroxide production (H2O2) in rat liver microsomes was investigated in vitro. LPO was determined as production of thiobarbituric acid reactants (TBAR). Different tri-, di- and monohydroxylated bile acids and cholesterol were given to the incubation mixture in concentrations ranging from 10(-5) to 10(-3) M. Sodium salts of cholic, tauroglycocholic and deoxycholic acids as well as cheno-deoxycholic, ursodeoxycholic, lithocholic acids and cholesterol did not alter the microsomal production of TBAR. H2O2 formation was significantly decreased by sodium deoxycholate whereas cholesterol increased H2O2 production up to 4 times. These results show that bile acids were not able to protect microsomal membrane lipids against peroxidative damage. Cholesterol mediated H2O2 formation as a source of hydroxyl radicals had no toxic effect concerning LPO, TBAR were not enhanced significantly.


[The mechanical behavior and biocompatibility of different modern ideas of partial fixed free-end saddle dentures]. This research is aimed to check the mechanical holding and the biocompatibility at various conceptions of removable partial dentures with free saddles, constituted from satellite alloys. As a matter of fact, the duality of the supporting surface in this kind of dental prosthesis sets biological problems, that one must try to sort out in the best way. It consists of three in vitro experimentations to point out the type or the types of framework answering in the best way to biomechanical and biological requirements. The very same equipment has been used on that three experimentations adapting it to the needs. It's "a machine to overdrive", imagined into the building of "L'Ecole supérieure d'Aéronautique de Toulouse"; this machine is made of an electric engine with an axis of rotation, of two speed reducers giving a motion, of one turn by second, of a knee-joint converting a rotary motion to an alternating motion, of a lever-arm enclosing supporting the weights, of a needle with a foam point which secure the saddles or the strategic zones, of two supporting mandibular and maxillary framework resin patterns, and on the areas representing the osteo-mucosa support capped uniformly with a compressible silicone material of on millimetre thick, of one dynamometer and of an accurate comparator to check the strength used, and the displacement tested zones. The first part consists in testing the amplitude of the saddle displacement and the mobilization of strategic joining areas from various frameworks used. So we can infer the impact on the mucosa during the function. That is why six types of frameworks have been achieved in Wironit satellite alloy showing mechanical qualities admitted to be excellent and to be subject to very accurate experiment conditions with 30 Kz strength (Lundeen and Gibbs, 1982). The results are interpreted through the reading of histograms which X-AXIS represent the points where motions have been located and the Y-AXIS represent the motion at 1/100th millimetre. It allows to show the existence more or less important of the saddle displacement which is not far from the mucosa one and constitute therefore on the biological view point a favourable component but also the existence of tensions in level of some strategic zones which let foresee, for same, a risk of weariness.(ABSTRACT TRUNCATED AT 400 WORDS)


The glycosaminoglycans in cultures of stimulated rat peritoneal macrophages. 1. Pattern and biosynthesis of glycosaminoglycans. Macrophages produce and secrete proteoglycans. They are involved in inflammation and may contribute to the glycosaminoglycans (GAG) and proteoglycans (PG) characteristic of the inflamed area. This possible contribution was studied with rat peritoneal macrophages (pMP) in vitro. The total amount, composition, and neosynthesis of the GAG (as the main constituents of PG) were determined in cultured pMP of normal rats or rats pretreated with casein, BCG, thioglycolate or carrageenan. Partly the stimulated pMP were further activated with LPS or PMA. The rat pMP contained non-sulfated GAG, chondroitin sulfate and heparan sulfate but no dermatan sulfate. The GAG amount per cell increased with duration of the culture. In most cases the final level of GAG roughly corresponded to that of 12 micrograms hexuronic acid per 10(6) cells. It was lower after BCG stimulation (25%) and higher in pMP stimulated by both casein and LPS (200%). The average percentage of the GAG secreted (40%) was enhanced with pMP stimulated by carrageenan (87%) or casein plus LPS (69%). The pattern of the GAG in cultural media, cell coat and cells differed markedly. Thus the cell coat contained a higher amount of heparan sulfate. Differences due to stimulation were mainly seen in the reduced sulfation of the CS-proteoglycan secreted (casein-, BCG-pMP). According to studies on the incorporation of 35S-sulfate and 3H-acetate the GAG of the cell coat are less labeled and more conservative. The bulk of newly synthesized GAG/PG is secreted. This secretion appears an important property of macrophages the cause of which is speculative.


Influence of low birth weight on subsequent reproductive performance of female rats. Female rats which were born underweight had lower absolute body mass throughout the whole experimental period than female litter mates with normal birth weight (controls). Their reproductive performance observed during three consecutive pregnancies was not different from that of controls except for lower litter size in the 1st pregnancy. Thus at least for rats, low spontaneous birth weight of females does not indicate subsequent poor pregnancy outcome.


Developmental malformations of human tongue and associated syndromes (review). The development of the tongue begins as known, in the floor of the primitive oral cavity, when the human embryo is four weeks old. More specifically, the tongue develops from the region of the first three or four branchial arches during the period that the external face develops. Malformations of the tongue, are structural defects, present at birth and happening during embryogenesis. The most common malformations are: 1. Aglossia 2. Microglossia, which is always combined with other defects and syndromes, like Moëbius syndrome 3. Macroglossia, which is commonly associated with cretinism, Down's syndrome, Hunter's syndrome, Sanfilippo syndrome and other types of mental retardation 4. Accessory tongue 5. Long tongue 6. Cleft or Bifid tongue, condition very usual in patients with the orodigitofacial syndrome 7. Glossitis Rhombica Mediana, a developmental malformation? 8. Lingual thyroid. Malformations are extensively analysed and discussed.


Characterization of YB2/0 cell line by counterflow centrifugation elutriation. The non-secreting rat myeloma cell line YB2/0 could be separated into different cell fractions by counterflow centrifugal elutriation. The obtained fractions are analyzed by morphology studies, morphometrics, clonogenic assays and flow cytometry. The methodology is extensively described. A separation of different cell fractions according to cell cycle stages was achieved. This implies further application possibilities for clinical use like the in vitro fractionation of autologous bone marrow prior to transplantation in patients with multiple myeloma.


Population cytogenetics.

Population cytogenetics. Chromosome variants are well established as useful genetic markers and integral components both of the genetic structure of populations, and in speciation. The current explosion of molecular techniques is facilitating the localization of many DNA sequences, while a reassessment of the fitness of chromosome mutants challenges some classical views on polymorphism and polytypy. Recent experiments on hybrid zones and mathematical modelling have greatly clarified the formation and evolution of chromosome races.


Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. The cingulate gyrus is a major part of the "anatomical limbic system" and, according to classic accounts, is involved in emotion. This view is oversimplified in light of recent clinical and experimental findings that cingulate cortex participates not only in emotion but also in sensory, motor, and cognitive processes. Anterior cingulate cortex, consisting of areas 25 and 24, has been implicated in visceromotor, skeletomotor, and endocrine outflow. These processes include responses to painful stimuli, maternal behavior, vocalization, and attention to action. Since all of these activities have an affective component, it is likely that connections with the amygdala are critical for them. In contrast, posterior cingulate cortex, consisting of areas 29, 30, 23, and 31, contains neurons that monitor eye movements and respond to sensory stimuli. Ablation studies suggest that this region is involved in spatial orientation and memory. It is likely that connections between posterior cingulate and parahippocampal cortices contribute to these processes. We conclude that there is a fundamental dichotomy between the functions of anterior and posterior cingulate cortices. The anterior cortex subserves primarily executive functions related to the emotional control of visceral, skeletal, and endocrine outflow. The posterior cortex subserves evaluative functions such as monitoring sensory events and the organism's own behavior in the service of spatial orientation and memory.


Biology and applications of human minisatellite loci. Highly repetitive minisatellites' include the most variable human loci described to date. They have proved invaluable in a wide variety of genetic analyses, and despite some controversies surrounding their practical implementation, have been extensively adopted in civil and forensic casework. Molecular analysis of internal allelic structure has provided detailed insights into the repeat-unit turnover mechanisms operating in germline mutations, which are ultimately responsible for the extreme variability seen at these loci.


Early breakdown of dendritic bundles in the retrosplenial granular cortex of hypertensive rats: prevention by antihypertensive therapy. Layer II pyramidal neurons in retrosplenial granular cortex (Rg) give rise to apical dendrites that bundle together tightly in layer Ic and Ib and spread out in layer Ia, where they arborize extensively. These dendritic bundles in Rg become disorganized in very old rats. Since hypertensive rats appear to age more rapidly than normotensive rats, we tested the hypothesis that the disorganization of the dendritic bundles in layer I of Rg is present at a much earlier age in hypertensive rats [spontaneously hypertensive rats (SHR)] compared to normotensive rats [Sprague-Dawley rats (SD)]. Further, we tested the hypothesis that long-term, antihypertensive drug treatment (captopril) prevents or attenuates the breakdown of the dendritic bundles in Rg of SHR. The retrograde tracer Fluorogold was injected into Rg to document the morphology of the apical dendrites of the layer II Rg neurons. In 4-month-old SD and SHR, most densely labeled layer II neurons have labeled apical dendrites that are confined to the dendritic bundles in layer Ib and Ic, and these dendrites arborize extensively only in layer Ia of Rg. In 14-month-old SD this pattern is preserved, but in contrast, in 14-month-old SHR most of the labeled apical dendrites lie outside the bundles, and less than half these dendrites reach layer Ia. Chronic antihypertensive therapy significantly attenuates this disorganization in 14-month-old SHR. These data indicate that in SHR, the layer II neurons in Rg are highly vulnerable to the combined effects of hypertension and aging, and the results suggest that hypertension is a primary contributor to these structural alterations.


DNA fingerprinting in non-human populations. DNA fingerprinting of non-human populations is beginning to fulfill its early promise, and in the past year there has been a flush of papers on mammalian breeding systems. However, many people, particularly field workers, believe that progress in this area has been slow. Attention is now focused on two amenable alternatives: microsatellite polymorphisms and randomly amplified polymorphic DNA. Of these, it is probable that microsatellites hold the key to rapid, efficient and highly informative screening of the genetic variability that exists within natural populations.


Genetic relationships among the apes and humans. Epistemological difficulties and contradictory sets of molecular genetic data show that the question 'What is our closest living relative?' is surprisingly difficult to answer decisively. It is highly likely that we have not a single closest relative but, at the genus level, two equally close ones.


Mammalian sex chromosomes: design or accident? Mammalian sex chromosomes evolved (and are still evolving) from a homomorphic pair by the progressive loss of active genes from the Y chromosome. Among the changes that have accompanied this differentiation, it is difficult to determine causes, effects and correlates. Comparative studies suggest that the choice of a gene, and thus a chromosome pair, to control the sex-determining pathway may be quite arbitrary, and that sex chromosomes and sex-determining genes are more likely to be the products of random changes than the products of selection for function.


Attention and sentence processing deficits in Parkinson's disease: the role of anterior cingulate cortex. Parkinson's disease (PD) is a complex neurodegenerative condition involving a motor disorder that is related to reduced dopaminergic input to the striatum. Intellectual deficits are also seen in PD, but the pathophysiology of these difficulties is poorly understood. Regional cerebral blood flow (rCBF) was studied in neurologically intact subjects during the performance of attention-demanding, sentence processing tasks using positron emission tomography (PET). The results demonstrated significantly increased rCBF in a distributed set of cerebral regions during the detection of an adjective or a particular agent in a sentence, including anterior cingulate cortex, left inferior and middle frontal cortex, left inferior temporo-occipital cortex, posterolateral temporal cortex, left caudate, and left thalamus. We identified defects in this cerebral network by studying PD patients with two PET techniques. Resting PET studies revealed a significant correlation between regional cerebral glucose metabolism in anterior cingulate cortex and deficits in attending to subtle grammatical aspects of sentences. Studies of PD patients with the PET activation technique revealed little change in anterior cingulate and left frontal CBF during performance of the adjective detection or agent detection tasks. These data suggest that a defect in anterior cingulate cortex contributes to the cognitive impairments observed in PD.


Reorganization of cingulate cortex in Alzheimer's disease: neuron loss, neuritic plaques, and muscarinic receptor binding. Pathology related to dementia of the Alzheimer type (DAT) develops later in cingulate cortex than in medial temporal areas. Therefore, end-stage cases have earlier forms of pathology in cingulate cortex, and postmortem studies of this region may provide a window on processes that temporal cortices pass through decades before death. Five classes of DAT have been described on the basis of neuron degeneration and receptor binding in posterior cingulate cortex. The present study assessed binding of 3H-oxotremorine-M with pirenzepine (OXO-M/PZ), a protocol for presynaptic muscarinic receptors, and thioflavin S-stained neuritic plaques (NPs) in cingulate area 23a in 12 DAT cases distributed over four classes of pathology and in nine age-matched control cases. OXO-M/PZ binding was significantly elevated in layers I, II, IV, and VI of all DAT cases and was very high in layer V compared to control cases. Almost 75% of the layer Va increase was due to binding in classes 2 and 3, while classes 1 and 4 were least affected. In class 3 cases, neuron density in layer Va was inversely correlated with OXO-M/PZ binding (r = -0.98) and primitive NP densities (r = -0.93). The close association between neuron densities and presynaptic muscarinic ligand binding in some classes confirms that there are independent classes of DAT. The high and inverse correlations between cortical pathology and ligand binding in class 3 cases suggest that there is a progression in class 3 pathology. Finally, elevated OXO-M/PZ binding and a report of increased choline uptake suggest that cholinergic axons sprout in DAT, and this sprouting may be associated with a progressive loss of postsynaptic elements.


The evolution of protein domains and the organizational complexities of metazoans. There is an increasingly heated debate on the very existence of a 'universe of exons' and on the types of genomes that existed after the RNA world. What has been lost in the excitement are the biological issues that relate to the rapid emergence of phenotypic novelties. These issues can be examined by integrating data on protein domains and genomic evolution with the geochemical and palaeontological records.


Posterior cingulate cortex: sensory and oculomotor properties of single neurons in behaving cat. The posterior cingulate cortex of the cat is strongly linked to cortical areas with sensory and oculomotor functions. We have now recorded from feline posterior cingulate neurons in order to determine whether they are active in conjunction with sensory events and eye movements. The results described here are based on monitoring the electrical activity of 195 single neurons in the posterior cingulate cortex of three cats equipped with surgically implanted scleral search coils and trained to fixate visual targets. Posterior cingulate neurons carry tonic orbital position signals and are phasically active in conjunction with saccadic eye movements. Activity related to eye movements and gaze is attenuated but not abolished by the elimination of visual feedback. Posterior cingulate neurons also are responsive to visual, auditory, and somatosensory stimulation. Systematic testing with visual stimuli revealed that responses are sharply reduced due to refractoriness at rates of stimulation greater than a few per second. These results conform to the theory that posterior cingulate cortex is involved in processes underlying visuospatial cognition.


Position effect and related phenomena.

Position effect and related phenomena. Position-effect variegation in Drosophila, the mosaic expression of genes juxtaposed to heterochromatin, remains an enigmatic long-range phenomenon. While the chromatin-conformation model has been challenged, compelling contrary evidence is lacking. Nevertheless, progress has been made in the genetic and molecular analysis of genes involved in the process of heterochromatin formation and in the characterization of genetic elements normally located in pericentric heterochromatin. In addition, telomeric position effect in yeast provides a new model system for the study of the quasi-stable inheritance of an inactivated state.


Nuclear architecture in plants.

Nuclear architecture in plants. Nuclei are dynamic structures that move through the mitotic cell cycle, are involved in differentiation, and divide and fuse during reproduction. The DNA contents of nuclei from different plants vary by 2500-fold. The design and structure of nuclei is, therefore, both flexible and versatile. Features relating to genome, chromosome, and maybe even gene localization during interphase are now emerging. At the chromosomal level, studies of scaffold associations and DNA sequence organization are indicating structures that impose nuclear architecture.


Chloroplasts.

Chloroplasts. New features of chloroplast gene expression are continually being discovered, particularly in the area of post-transcriptional RNA processing. RNA editing of chloroplast pre-mRNAs occurs in both monocotyledons and dicotyledons, and involves both initiator and internal codons. The view of introns as mobile genetic elements expands both with the identification of additional twintrons in Euglena chloroplast genes and with studies on the homing group I introns of Chlamydomonas.


Polymerase evolution and organism evolution. The continuing exploration of the structure-function relationships of polymerases and the use of polymerases as phylogenetic tools complement each other, as seen in the literature for the past year. DNA-dependent RNA-polymerase gene sequences, in particular, have been used both to define functional domains in the protein encoded and recently to explore fundamental questions in evolution.


Selection-induced mutations.

Selection-induced mutations. Some spontaneous mutations are specifically 'adaptive' in two ways: in that they occur more often when they are useful than when they are irrelevant to the survival of the cell; and in that they occur as specific responses to selective pressures. These 'selection-induced mutations' occur both in bacteria and in the eukaryotic microorganism, yeast.


Sleep and dreaming: induction and mediation of REM sleep by cholinergic mechanisms. The most important recent work on the neurobiology of sleep has focused on the precise cellular and biochemical mechanisms of rapid eye movement sleep mediation. Direct and indirect evidence implicates acetylcholine-containing neurons in the peribrachial pons as critical in the triggering and maintenance of rapid eye movement sleep. Other new studies provide support for the hypothesis that the cholinergic generator system is gated during waking by serotonergic and noradrenergic influences. A growing consensus regarding the basic neurobiology has stimulated new thinking about the brain basis of consciousness during waking and dreaming.


Neuronal basis of behavior.

Neuronal basis of behavior. In addition to describing behavior in terms of neuronal properties and interconnections, some studies are using these well defined neuronal circuits to see how the circuits interact, how they develop, and how they are modified by experience, hormones and neuromodulators. The ready availability of computers and computational techniques has helped in some efforts, as have improvements in physiological and morphological techniques. The major insights, however, still come from experiments that ask clear and direct questions. This review highlights some of the promising approaches and suggests some general features of how neuronal circuits produce behavior.


The cerebellum and motor learning.

The cerebellum and motor learning. Lesions of the cerebellum and its associated circuitry abolish or impair several types of motor learning. It is controversial whether these lesions damage the motor memory or its performance. Recent work is evaluated in the light of the original suggestions by Marr, Albus and Gilbert that the cerebellar cortex is a preferred locus for reflex plasticity and motor learning.


Automatic control of limb movement and posture. Studies are reviewed that address the problem of the variables controlled by the central nervous system in the maintenance of body posture and limb movement against disturbing forces. The role of global variables of control, which take into account the dynamic state of the limb, is discussed. Neural substrates that are involved in the distributed control of kinematic and dynamic parameters are also considered.


Sensory-motor coordination during grasping and manipulative actions. Goal-directed grasping and manipulation of objects are human skills that depend on automatic sensory control in which predictive feed-forward mechanisms integrate somatosensory and visual signals with sensory-motor memory systems. Memory representations of physical and task-relevant properties of the object play a pivotal role. Anticipatory strategies are crucial when purposeful actions arise from learned relationships between afferent patterns and efferent commands. The development of even elementary precision grip skills is a protracted process not concluded until early adolescence. Not surprisingly, the neural control of manual actions engages most central nervous system areas known to be involved in motor control.


Role of proprioceptors in neural control. The conventional notion that peripheral muscle-related signals provide the basis for resistance to external perturbations is no longer sufficient. Proprioceptive information seems to be required for spatial steering of multi-joint movements, and also for temporal coordination among the joints in certain tasks. In rhythmic movements, peripheral and centrally generated signals appear to interact in a complementary manner. The complex effects of proprioceptive afferents on motor output continue to be delineated vigorously. Global effects of local perturbation in multi-joint contexts are emerging as being particularly significant.


The prefrontal cortex and internally generated motor acts. The neuroanatomical and neurophysiological data that have been obtained from experimental primates are converging on a framework for understanding the prefrontal influence on motor output. The framework isolates internally memory-based functions from externally guided sensory-based functions, identifies the internally-based functions with prefrontal circuits, the sensory-based functions with premotor circuits, and integrates the specializations of prefrontal, premotor and subcortical structures in the control of motor acts.


Medial wall motor areas and skeletomotor control. The results of recent studies in primates provide convincing evidence that the cortex on the medial wall of the hemisphere contains multiple areas concerned with the generation and control of body movement. Highlights of these findings include the demonstration that each of these motor areas has substantial direct projections to the spinal cord, somatotopically organized projections to the primary motor cortex, a 'motor' map, revealed by intracortical stimulation, and neuronal activity that precedes trained hand movements.


Evidence for the lateral intraparietal area as the parietal eye field. It has long been appreciated that the posterior parietal cortex plays a role in the processing of saccadic eye movements. Only recently has it been discovered that a small cortical area, the lateral intraparietal area, within this much larger area appears to be specialized for saccadic eye movements. Unlike other cortical areas in the posterior parietal cortex, the lateral intraparietal area has strong anatomical connections to other saccade centers, and its cells have saccade-related responses that begin before the saccades. The lateral intraparietal area appears to be neither a strictly visual nor strictly motor structure; rather it performs visuomotor integration functions including determining the spatial location of saccade targets and forming plans to make eye movements.


Hypothalamic neuropeptide Y regulation of feeding and energy metabolism. Neuropeptide Y is an important regulator of energy intake and expenditure. The central portion of this regulatory system appears to reside in the arcuate nucleus/paraventricular nucleus of the hypothalamus. The effects of neuropeptide Y on energy metabolism include increased food intake, decreased thermogenesis and increased white fat storage.


Functional homologs of the Arabidopsis RPM1 disease resistance gene in bean and pea. We showed that a bacterial avirulence (avr) gene function, avrPpiA1, from the pea pathogen Pseudomonas syringae pv pisi, is recognized by some, but not all, genotypes of Arabidopsis. Thus, an avr gene functionally defined on a crop species is also an avr gene on Arabidopsis. The activity of avrPpiA1 on a series of Arabidopsis genotypes is identical to that of the avrRpm1 gene from P.s. pv maculicola previously defined using Arabidopsis. The two avr genes are homologous and encode nearly identical predicted products. Moreover, this conserved avr function is also recognized by some bean and pea cultivars in what has been shown to be a gene-for-gene manner. We further demonstrated that the Arabidopsis disease resistance locus, RPM1, conditioning resistance to avrRpm1, also conditions resistance to bacterial strains carrying avrPpiA1. Therefore, bean, pea, and conceivably other crop species contain functional and potentially molecular homologs of RPM1.


Downstream DNA sequences are required to activate a gene expressed in the root cortex of embryos and seedlings. We showed previously that a gene, designated AX92, which is expressed at an early stage of cortex differentiation in the root apex of oilseed rape seedlings, is also expressed in embryos. To compare AX92 gene regulation during embryo-genesis and postembryonic growth, we constructed a chimeric gene consisting of AX92 5' and 3' untranslated and flanking regions fused with a beta-glucuronidase protein coding region. We showed that the chimeric gene is active in both developing cortex cells in the root apical meristems of transgenic oilseed rape seedlings and in cortex cells at the root end of embryonic axes. To determine whether the AX92 gene is regulated by a common mechanism in embryos and seedlings, we analyzed the expression of modified chimeric genes. We showed that the AX92 chimeric gene is regulated combinatorially and that DNA sequences located 3' of the protein coding region are necessary for its activation in the root cortex of both embryos and seedlings. Our results suggest that common regulatory sequences are required to activate the gene in the embryonic and postembryonic root cortex.


Regional and cell-specific gene expression patterns during petal development. We investigated gene expression patterns that occur during tobacco petal development. Two petal mRNA classes were identified that are present at elevated levels relative to other organs. One class is represented equally in the unpigmented tube and pigmented limb regions of the corolla. The other class accumulates preferentially within the limb region. Limb-specific mRNAs accumulate at different times during corolla development, peak in prevalence prior to flower opening, and are localized in either the epidermal cell layers or the mesophyll. The epidermal- and mesophyll-specific mRNAs change abruptly in concentration within a narrow zone of the limb/tube border. Preferential accumulation of at least one limb-specific mRNA occurs within the corolla upper region early in development prior to limb maturation and pigment accumulation. Limb-specific mRNAs also accumulate preferentially within the unpigmented corolla limb region of Nicotiana sylvestris, a diploid progenitor of tobacco. Runoff transcription studies and experiments with chimeric beta-glucuronidase genes showed that petal gene organ, cell, and region specificities are controlled primarily at the transcriptional level. We conclude that during corolla development transcriptional processes act coordinately on limb-specific genes to regulate their regional expression patterns, but act individually on these genes to define their cell specificities.


An Arabidopsis mutant defective in the general phenylpropanoid pathway. Mutants of Arabidopsis deficient in a major leaf phenylpropanoid ester, 2-O-sinapoyl-L-malate, were identified by thin-layer chromatographic screening of methanolic leaf extracts from several thousand mutagenized plants. Mutations at a locus designated SIN1 also eliminate accumulation of the sinapic acid esters characteristic of seed tissues. Because of increased transparency to UV light, the sin1 mutants exhibit a characteristic red fluorescence under UV light, whereas wild-type plants have a blue-green appearance due to the fluorescence of sinapoyl malate in the upper epidermis. As determined by in vivo radiotracer feeding experiments, precursor supplementation studies, and enzymatic assays, the defect in the sin1 mutants appears to block the conversion of ferulate to 5-hydroxyferulate in the general phenylpropanoid pathway. As a result, the lignin of the mutant lacks the sinapic acid-derived components typical of wild-type lignin.


Gibberellin-responsive elements in the promoter of a barley high-pI alpha-amylase gene. Deletion analysis has previously shown that the major gibberellic acid (GA)- and abscisic acid (ABA)-responsive elements in the promoter of a high-pI alpha-amylase gene of barley are located downstream of -174 (Jacobsen and Close, 1991). We have used transient expression assays in barley aleurone protoplasts to identify sequences between -174 and +53 that confer GA and ABA responsiveness on expression of a beta-glucuronidase reporter gene. Using alpha-amylase promoter fragments and synthetic oligonucleotides fused to minimal promoters, we have shown that the hormone-responsive region is located between -174 and -108. A single copy of this region fused to a minimal alpha-amylase promoter (-41) conferred both GA- and ABA-responsive expression on the reporter gene comparable to the positive control, Am(-174)IGN. Multiple copies of this region were able to activate even greater levels of expression. Site-directed mutagenesis was used to determine the functional importance of the conserved motifs (-169pyrimidine box, -143TAACAAA box, and -124TATCCAC box) and nonconserved intervening sequences within the region between -174 and -108. Our results showed that both the TAACAAA and TATCCAC boxes play an important role in GA-regulated expression. We propose that the TAACAAA box is a gibberellin response element, that the TATCCAC box acts cooperatively with the TAACAAA box to give a high level of GA-regulated expression, and that together these motifs form important components of a gibberellin response complex in high-pI alpha-amylase genes. The TAACAAA box also appears to be the site of action of ABA.(ABSTRACT TRUNCATED AT 250 WORDS)


Definition and functional implications of gibberellin and abscisic acid cis-acting hormone response complexes. The mechanisms by which cis-acting hormone response elements affect transcription is unclear. In this study, we demonstrated that a second "coupling element," identified as O2S, must be present to allow a single copy of either the gibberellin response element (GARE) or the abscisic acid response element (ABRE) to mediate their hormonal effects in the barley Amy32b alpha-amylase gene promoter. The interactive effects of the O2S and the GARE are constrained positionally and spatially; thus, together they form a gibberellin response complex (GARC). The absolute requirement of the O2S for function of the ABRE demonstrates that these together form an abscisic acid response complex (ABRC). A second copy of the GARE can substitute for the O2S in the GARC, but only in one orientation. By expressing the GARC-containing and ABRC-containing promoters in developing aleurone tissue, we showed that hormonal effects prevent alpha-amylase gene expression during the second half of grain development, but other mechanisms suppress expression earlier. Our results suggest that the specific sequence serving as a coupling element in a given gene promoter will greatly affect where and when the GARE or ABRE will be able to regulate transcription.


Alternative 3' splice acceptor sites modulate enzymic activity in derivative alleles of the maize bronze1-mutable 13 allele. The defective Suppressor-mutator (dSpm)-induced allele bronze1-mutable 13 (bz1-m13) and many of its derivative alleles are leaky mutants with measurable levels of flavonol O3-glucosyltransferase activity. This activity results from splicing at acceptor site-1, one of two cryptic 3' splice sites within the dSpm insertion in bz1-m13. In this study, splicing in bz1-m13 change-in-state (CS) alleles CS-3 and CS-64 was shown to be altered from bz1-m13; previous work found altered splicing in CS-9. CS-64 is a null allele and lacks the acceptor site-1-spliced transcript because this site is deleted. CS-3 and CS-9 had increased levels of the acceptor site-1 transcript relative to bz1-m13 and increased enzymic activities. A deletion in CS-9 altered splicing by eliminating acceptor site-2. Both acceptor sites were intact in CS-3, but a deletion removed most of a 275-bp GC-rich sequence in dSpm. This suggests that GC-rich sequences affect splicing and is consistent with models postulating a role for AU content in the splicing of plant introns. Splicing does not necessarily occur, however, at the junction of AU-rich intron sequences and GC-rich exon sequences.


Electroacupuncture in fibromyalgia: results of a controlled trial. To determine the efficacy of electroacupuncture in patients with fibromyalgia, a syndrome of unknown origin causing diffuse musculoskeletal pain. Three weeks' randomised study with blinded patients and evaluating physician. University divisions of physical medicine and rehabilitation and rheumatology, Geneva. 70 patients (54 women) referred to the division for fibromyalgia as defined by the American College of Rheumatology. Patients were randomised to electroacupuncture (n = 36) or a sham procedure (n = 34) by means of an electronic numbers generator. Pain threshold, number of analgesic tablets used, regional pain score, pain recorded on visual analogue scale, sleep quality, morning stiffness, and patient's and evaluating physician's appreciation. Seven of the eight outcome parameters showed a significant improvement in the active treatment group whereas none were improved in the sham treatment group. Differences between the groups were significant for five of the eight outcome measures after treatment. Electroacupuncture is effective in relieving symptoms of fibromyalgia. Its potential in long term management should now be studied.


Tobacco and myocardial infarction: is snuff less dangerous than cigarettes? To estimate the risk of myocardial infarction in snuff users, cigarette smokers, and non-tobacco users in northern Sweden, where using snuff is traditional. Case-control study. Northern Sweden. All 35-64 year old men who had had a first myocardial infarction and a population based sample of 35-64 year old men who had not had an infarction in the same geographical area. Tobacco consumption (regular snuff dipping, regular cigarette smoking, non-tobacco use) and risk of acute myocardial infarction. 59 of 585 (10%) patients who had a first myocardial infarction and 87 of 589 (15%) randomly selected men without myocardial infarction were non-smokers who used snuff daily. The age adjusted odds ratio for myocardial infarction was 0.89 (95% confidence interval 0.62 to 1.29) for exposure to snuff and 1.87 (1.40 to 2.48) for cigarette smoking compared with non-tobacco users, showing an increased risk in smokers but not in snuff dippers. Regular cigarette smokers had a significantly higher risk of myocardial infarction than regular snuff dippers (age adjusted odds ratio 2.09; 1.39 to 3.15). Smoking, but not snuff dipping, predicted myocardial infarction in a multiple logistic regression model that included age and level of education. In middle aged men snuff dipping is associated with a lower risk of myocardial infarction than cigarette smoking.


Risk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study. To determine whether obstetric complications occur to excess in the early histories of individuals who go on to develop schizophrenia when compared with controls, and to seek clinical correlates of any such excess. Contemporaneous maternity hospital records were identified and extracted verbatim, and these extracts evaluated for obstetric complications by two independent assessors who were blind to subjects' status. 65 patients having an ICD-9 diagnosis of schizophrenia, the records of the previous same sex live birth being deemed to be those of a control subject. Presence of one or more obstetric complications recorded in maternity notes of patients and controls. When two recognised scales for specifying obstetric complications were used the patients with schizophrenia were significantly more likely than controls to have experienced at least one obstetric complication (odds ratio 2.44, 95% confidence interval 1.08 to 6.03). Patients also showed a greater number and severity of and total score for obstetric complications, fetal distress being the only complication to occur to significant individual excess (present in five (8%) patients, absent in controls). There was a marked sex effect, male patients being more vulnerable (odds ratio 4.24, 1.39 to 12.90) to such complications. Obstetric complications in patients were unrelated to family history or season of birth but were associated with a significantly younger age at onset of illness (mean difference--4.5 years,--1.2 to--7.8 years). Patients with schizophrenia, particularly males, have an excess of obstetric complications in their early developmental histories, and such complications are associated with a younger age at onset of their disease. Though the data are not conclusive, they also suggest that obstetric complications may be secondary to yet earlier events.


Discovery of antibodies.

Discovery of antibodies. Passive immunisation has been used in clinical practice since the end of last century, mainly for prophylaxis. Success of early treatments was marred by anaphylactic reactions and serum sickness because antibodies or antitoxins were not raised in humans. Recombination of gene segments during antibody synthesis means that specific antibodies for numerous antigens can be produced from a limited gene pool. Killer lymphocytes, phagocytes, and complement then bind to the constant region of the antibody facilitating elimination of the pathogen. Development of a method of obtaining large quantities of antibodies against a specific antigen (monoclonal antibodies) offers the possibility of initiating host defence mechanisms against any unwanted antigen, though some problems still remain in preventing the body from attacking the monoclonal antibody.


Maintaining excellence: the preservation and development of specialised services. The advent of the Tomlinson inquiry draws attention to the need to strike a balance between market led and planned approaches to health care delivery. This is important not just for hospital rationalisation but also for the preservation and development of services which are provided in a smaller number of hospitals. Specialised services are often in the forefront of raising standards of care and introducing new developments and innovations. They are the only option for a small number of patients with serious illnesses. In the internal market for health care provision created by the 1990 NHS reforms more sophisticated and flexible mechanisms must be found to provide stability for specialised services while at the same time enabling the benefits of purchaser choice and provider competition to be realised.


Using a mock trial to make a difficult clinical decision. Many clinical decisions have to be taken with inadequate scientific information. Reaching a consensus among experts has been tried as one response to this problem. Another, described here, is to use legal process to dissect a difficult question. In this case a mock trial--using barristers, expert witnesses, and a jury--was conducted on whether bone marrow transplantation should be offered to all children with symptomatic sickle cell disease. Transplantation seems to offer about a 90% cure rate for a condition that may kill 15% of children before they reach 20. But transplantation carries a 10% risk of death or severe disability, and doctors cannot predict which children will suffer severely from their sickle cell disease and which will suffer little or nothing. The jury eventually reached a majority decision that transplantation should not be offered now to all symptomatic children.


[Intensive care of tumor patients].

[Intensive care of tumor patients]. There is no substantial difference in the prognosis of cancer patients after intensive care compared to certain other groups of patients except for the tumor patient with major respiratory problems. Hence, the general refusal of intensive care for cancer patients is not justified. Rather indication for intensive care needs careful examination of several aspects including medical science and ethics. Particular ethical problems arising in intensive care for cancer patients can be reduced by open communication between the medical team and the patient as well as between the medical specialists.


Heterogeneity of immunohistochemical staining with pulmonary surfactant protein A among fractionated alveolar macrophages which involves metabolism of pulmonary surfactant. Alveolar macrophages (AM) which are separated into four fractionated subpopulations (I, II, III and IV), represented differential immunohistochemical staining with antibody against pulmonary surfactant protein A (SP-A). In light microscopy, the least dense AM (fraction I) were intensely stained with antibody to SP-A in numerous granules of the cytoplasm, whereas the most dense cells (fraction IV) showed immuno-reactivity with the antibody in several granules distributed in the spreading and elongating cytosol. By Western blot analysis, antibody to SP-A recognized a triplet of nature molecules of SP-A in AM lysate. However, the antigen of the AM lysate almost disappeared when the cells were cultured for more than two days, which indicate that AM do not synthesize SP-A and have digested intracellular SP-A during the cultivation. Immunoelectron microscopically, AM of fraction IV sometimes had very large vacuoles including lamellar body-like structures, probably pulmonary surfactant immediately after taken up from the alveolar lumen by them, which were heavily deposited with gold particles indicating antigenic site of SP-A. Whereas cells of fraction I contained numerous cytoplasmic vacuoles that were frequently labelled with the immuno-gold particles and were not associated with lamellar body-like structures, which may indicate that the materials in the vacuoles are digesting. The results of this experiments suggest that pulmonary surfactant, layered on the alveolar epithelium, is in part taken up by higher dense AM and is digested during a process of their maturation in the direction of lower dense cells, which undergo an important role of metabolism of pulmonary surfactant by AM subpopulations.


The requirements for activation of an antigen specific T-cell clone via the CD3 complex. We have studied the requirements for the activation of the haemagglutinin peptide specific cloned T-cell HA1.7 by anti-CD3 antibodies and the mechanism of modulation of the CD3 complex. Cross-linking of the complex either by a soluble antibody second layer or an immobilized matrix of antibody is necessary for induction of a proliferative response. This proliferative response is totally dependent on exogenously added IL-2. Modulation of the cross-linked CD3 complex is by patching, capping and internalization of the antigen and is not essential for the proliferative response.


[Chances and risks of predictive medicine]. Ethical reasoning for predictive medicine is closely related to evaluating its chances and risks, for the individual (including future generations) and society. An optimistic viewpoint will emphasize the chances of predictive medicine. Yet it will be of great importance to differentiate overall political perspectives and the effects of any single operational step in regard to its life saving properties. Whenever predictive medicine leads to irresponsible risk it has to be disapproved of.


[Ethical questions of prenatal medicine]. The paper presents data on prenatal human development studied by non-invasive sonography. Furthermore clinical application of prenatal diagnostic procedures and their possibilities in the future are discussed. These facts are the basis of ethical judgement in prenatal medicine.


Inhibitory effect by 1,25-dihydroxyvitamin D3 on concanavalin A-stimulated proliferation of rat thymic lymphocytes. It has been reported that vitamin D3 derivatives promote the differentiation of monocytes into macrophages, while the derivatives suppress mitogen-stimulated proliferation of human peripheral blood-mononuclear cells (PBMC). However, their effect on thymic lymphocytes which are in the course of differentiation and maturation into T cells has not been thoroughly examined. The authors studied the inhibitory effect by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on concanavalin A (Con A)-stimulated proliferation of rat thymic lymphocytes and explored its mechanism. The proliferation of rat thymic lymphocytes stimulated with Con A was suppressed by 1,25-(OH)2D3 in a dose-dependent manner between a range of 10(-10) M to 10(-8) M. Because this suppressive action of 1,25-(OH)2D3 was markedly reduced by removal of coexisting adherent cells or by treatment with indomethacin which suppresses the prostaglandin E2 (PGE2) synthesis, it seems likely that PGE2, released from macrophages with the stimulation of 1,25-(OH)2D3, is involved in the suppressive action. Further studies on the inhibitory mechanism clarified that PGE2 from the contaminated macrophages suppressed the formation and release of interleukin-2 (IL-2), whereas the expression of IL-2 receptors on thymic lymphocyte with Con A stimulation was not affected. These results suggest that vitamin D3 derivatives might possibly contribute to regulation of in vitro proliferation of thymic lymphocytes.


23Na NMR evaluation of human erythrocytes Na+/K+/CL-cotransport. A study in elderly hypertensives. The behaviour of sodium transport systems across the cell membrane has been poorly investigated in elderly hypertension. Sodium efflux driven by Na+/K+/Cl-cotransport activity was therefore investigated (using a novel NMR-spectroscopy method) in 5 elderly hypertensive males (mean age 78 +/- 5 years) and 5 normotensive controls (mean age 79 +/- 3 years). In order to exclude any change in cotransport activity secondary to metabolic abnormalities, both patients and controls were non-obese and had normal glucose and lipid metabolisms. The Na+/K+/Cl-cotransport evaluation was performed after three months of pharmacological wash-out, under a diet containing 120 mEq of Na+/day. The resulting data showed that Na+ efflux due to outward Na+/K+/Cl-cotransport was higher in hypertensive group than in the normotensive one (0.50 +/- 0.10 mmol Na+/l cells/hr. vs 0.33 +/- 0.03 mmol Na+/l cells/hr., respectively, p < 0.05). Intracellular Na+ content was similar in both groups. At variance with previous data from the literature, our findings indicate that the Na+/K+/Cl-cotransport activity is elevated in elderly hypertensives.


[Basic principles of genetic counseling]. Genetic counseling and diagnosis are increasingly significant for individual and social life. In view of inherent practical and ethical problems in medical practice, the definition of rules in this field seems necessary. The paper provides a compilation and short argumentation of such rules. They should establish a certain qualitative standard and can serve as a foundation for future discussion.


[protein synthesis in alkylated bacteriophage T7]. We have studied the toxic effects of alkylating agents with a well characterized model: phage T7. Treatment of bacteriophage T7 with methyl methanesulfonate led to perturbation of phage-specific protein synthesis. Synthesis of class I and II proteins was prolonged, while production of class II and III proteins was delayed. This delay increased for proteins coded by genes located further to the right on the T7 genetic map. In extracts prepared from cells infected by alkylated phage, the specific activity of T7 RNA polymerase was decreased. These results suggest that the toxic action of methyl methanesulfonate is directed towards viral transcription.


DNase I digestion as a tool for the quantitative evaluation of C-heterochromatic-DNA in situ. The amount of DNA resisting the C-banding pre-treatments (C-heterochromatic-DNA) was found to account for the interspecific differences of genome size in different Primate groups. The evaluation of this parameter is therefore of great interest in cytotaxonomy. In this work, DNase I digestion was used instead of the pre-treatments C-banding, in an attempt to set up a suitable method for the quantitative evaluation of C-heterochromatic-DNA in both metaphase chromosomes and interphase chromatin. In fact DNase I is known to preferentially digest "active or potentially active" chromatin, and the highly repetitive and inactive DNA in C-heterochromatin should characteristically resist DNase I cleavage. As a model system, differently fixed mouse splenocytes were treated with DNase I for various times, and the digestion was monitored by flow cytometry after propidium iodide staining. In addition, mouse metaphase preparations from lymphocyte cultures were also digested with DNase I, and the amount of residual DNA was evaluated by static microfluorometry. Under controlled conditions of fixation, enzyme concentration, time and temperature, the same limit-digest can be obtained in both interphase nuclei and metaphases, which corresponds to the amount of residual DNA after C-banding and has a C-banding-like pattern in chromosomes.


The levels of vascular smooth as well as skeletal muscle actin mRNAs differ substantially among both myoblast and fibroblast lines with different skeletal myogenic potentials. Little is known about the factors which regulate vascular smooth muscle (vsm) actin gene expression during skeletal myogenesis in culture. We have therefore looked for differences in the levels of accumulation of vsm actin mRNA among six mouse cell lines differing in apparent myogenic potential or in the complement of myogenesis determination genes which they express: NIH 3T3 and 10T1/2 non-myogenic fibroblasts and four myogenic lines--3T3-MyoD1 and 10EMc11s, MyoD/myogenin expressing sublines of the fibroblast lines, derived by transfer into the parent lines of a MyoD cDNA expression construct; C2C12, which expresses all four known myogenesis determination genes; and BC3H1, which expresses myf-5, myogenin, little herculin, and no MyoD. In differentiated cells of all four myogenic lines, vsm actin mRNA was expressed at levels dramatically higher than in growth-arrested NIH 3T3 cells, consistent with expression of vsm actin mRNA as an intrinsic part of the skeletal myogenic program somehow directed by myogenesis determination gene products. Interestingly, however, the level of vsm actin mRNA in growth arrested C3H10T1/2 fibroblasts was also dramatically higher than that in NIH 3T3. In view of these findings, and of the relative ease with which 10T1/2 as opposed to NIH 3T3 cells can be converted to myogenic lines, we hypothesize that factors which can act to regulate vsm actin gene expression in the absence of myogenesis determination gene expression may also influence the skeletal myogenic potential of the cells in which they are found. Among the myogenic lines, the ratio of vsm to skm actin mRNA was highest in BC3H1 cells, raising the possibility that were these cells forced to express MyoD and/or more herculin, as do the other myogenic lines, the ratio would decrease. Thus both fibroblast and myogenic lines will be useful for investigating the mechanisms controlling skeletal myogenesis and vsm and skm actin gene expression during myogenesis.


Synthesis of a prolactin-like peptide by natural killer cells: positive regulation by CD16 and exogenous prolactin. We have previously shown that Prolactin (PRL) activates the native and the in vitro acquired cytotoxicity and the DNA synthetic activity of Natural Killer (NK) cells. Here we show that the supernatant and the cell lysate of NK cells express a 35S-labelled 50 kDa peptide specifically immunostained by two different PRL-antisera. The supernatant of NK cells was biologically active in a Nb2 assay and the activity could be adsorbed by an anti-PRL antiserum. The production of the PRL-like peptide only occurred when NK cells were isolated through binding to immobilized immunocomplexes, the biological ligand for CD16, and was positively modulated by exogenous PRL. These results indicate that PRL, produced by NK cells following stimulation, may act in an autocrine fashion to maintain and/or activate the NK cell function.


Macular disease in an elderly population. In order to obtain more accurate information concerning the prevalence of macular diseases in an elderly population, a clinical study was undertaken on a sample of 430 members of the general population over the age of 65 years in London. Degenerative age-related macular changes were clinically visible in about 25%, and 2.8% had a lesion causing loss of visual acuity due to macular disease. Age was the only risk factor identified for age-related changes. No correlation was identified with the prevalence of hypertension, smoking, or diabetes mellitus between groups. In addition, symmetry was shown in the number of drusen, as well as their size, density and fluorescence in the central and peripheral areas between the eyes of affected subjects. The prevalence data from this study represent a baseline for the interpretation of hospital-based data and for the planning of health care.


Systemic absorption of ocular cyclopentolate in children. Cyclopentolate plasma levels were quantitated and heart rate and pupil size were monitored after ocular application of the drug to juveniles. In all, 12 children were given one 35-microliters eyedrop of either 1% cyclopentolate (n = 6) or placebo (n = 6) in randomized order in the lower cul-de-sac of one eye. A sensitive radioreceptor assay was used to determine the systemic drug absorption. With the exception of one child, detectable cyclopentolate concentrations were seen in plasma at as early as 3 min after the ocular drug application. There was a marked interindividual variation in peak plasma cyclopentolate concentrations ranging from undetectably low to 5.8 ng/ml (median, 2.9 ng/ml). In some children a second drug concentration peak was detected. Cyclopentolate increased the pupillary diameter from 4.8 +/- 1 mm before drug application to 8 +/- 0.9 mm at 30 min after administration, but the children's heart rate did not alter.