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Biomedical subjects

J Ward

Publications and source records attributed to J Ward.

At least 307 records · Page 17Linked to original sources

Leishmania and Trypanosoma surface glycoproteins have a common glycophospholipid membrane anchor.

The variant surface glycoprotein (VSG) of the African trypanosomes is the major membrane protein of the plasma membrane of the bloodstream stage of the parasite. It is anchored in the plasma membrane by a glycolipid covalently bound to the C-terminal amino acid of the protein. The VSG is released through the action of a phosphatidylinositol-specific phospholipase C that removes dimyristoylglycerol and exposes the carbohydrate antigenic determinant common to all VSGs. Promastigotes of Leishmania have a predominant surface glycoprotein, termed p63, that is anchored in the plasma membrane in a similar way. A water-soluble form of p63 can be generated through the action of phosphatidylinositol-specific phospholipase C from trypanosomes or from Bacillus cereus. Either treatment exposes on the Leishmania p63 an antigenic determinant recognized by antibody prepared against the trypanosomal crossreacting determinant. These findings indicate that p63 and VSG have a common membrane anchor and are structurally related.

Animals↗

A survey of paediatric management practices in Down's syndrome.

Paediatricians throughout Australia and New Zealand completed a questionnaire in which they indicated the type of advice they normally give to parents of children with Down's syndrome. Results indicated strong support for early intervention, discussion with other parents of children with Down's syndrome, and conventional therapy services. Cosmetic surgery appears to be receiving increasing support. Megavitamin therapy, cell therapy and the Doman programme are unsupported. A tendency was noted for paediatricians to underestimate the developmental potential of children with Down's syndrome.

Child↗

Modification by lung inflation of the vascular responses from the carotid body chemoreceptors and other receptors in dogs.

The reflex effects of increasing pulmonary ventilation on the responses of the hind-limb and systemic vascular resistances to stimulation of the carotid body chemoreceptors and carotid sinus baroreceptors and to distension of the urinary bladder have been studied in the anaesthetized dog. A preparation was used incorporating total cardiopulmonary bypass to maintain the arterial blood gas composition constant when alterations in pulmonary ventilation were made. The regions of both carotid bifurcations, the arch of the aorta and the cerebral circulation were independently perfused at constant pressure so as to exclude secondary reflexes from arterial baroreceptors. Four levels of pulmonary ventilation were used: 0.095, 0.285, 0.475 and 0.665 l min-1 kg-1 body weight, at a constant frequency of 19 cycles min-1. Increasing the pulmonary ventilation per se in steps from 0.095 to 0.665 l min-1 kg-1 resulted in a significant progressive reduction in hind-limb and systemic vascular resistances which were shown to be due to a reflex from the lungs. Stimulation of the carotid body chemoreceptors by hypoxic hypercapnic blood resulted in an increase in hind-limb and systemic vascular resistances when carried out at each of the four levels of pulmonary ventilation. The size of the increases in vascular resistances, however, was progressively and significantly reduced as the pulmonary ventilation was increased. This partial inhibition of the carotid body reflex vasoconstrictor response was dependent on the innervation of the lungs. Stimulation or unloading of the carotid sinus baroreceptors by altering the perfusion pressure in the vascularly isolated carotid bifurcation regions caused a significant decrease and increase respectively in hind-limb and systemic vascular resistances at all four levels of pulmonary ventilation. Unlike the responses to chemoreceptor stimulation, the size of these responses was unaffected by the level of pulmonary ventilation. Distension of the urinary bladder resulted in a significant increase in hind-limb and systemic vascular resistances. The size of these responses was also unaltered by changing the level of pulmonary ventilation. These results indicate that there is an interaction between the inputs from the lungs and the carotid body chemoreceptors in the control of hind-limb and systemic vascular resistances. In contrast the inputs from the carotid sinus baroreceptors and the urinary bladder were unaffected by the input from the lungs.

Animals↗

Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia.

The cultured skin fibroblasts from three patients with lacticacidemia were found to have low rates of 1-[14C]pyruvate oxidation in the face of normal pyruvate dehydrogenase activity. After incubation with 1 mM glucose, these three cell strains also exhibited lactate/pyruvate ratios which were three times greater than those of controls. In two of the patients, both ATP and oxygen consumption in fibroblast mitochondrial preparations was deficient with NAD-linked substrates but normal with succinate and ascorbate/N'N'N'N' tetramethyl phenylene diamine. In the third patient, ATP synthesis in mitochondrial preparations was deficient with all substrates tested. Measurement of Rotenone-sensitive NADH-cytochrome c reductase in mitochondrial preparations from skin fibroblasts showed that two of the patients had 14 and 18%, respectively, of control activity. In the third patient, cytochrome oxidase activity was 15% of that in controls. We conclude that respiratory chain defects can be demonstrated in cultured skin fibroblasts with consistency using a number of different techniques.

Adenosine Triphosphate↗

Comparison of controlled-release diazepam capsules and placebo in patients in general practice.

A multi-centre, randomized double-blind parallel study was carried out to compare the efficacy and tolerance of a single daily dose of controlled-release (CR) capsules of diazepam (10 mg and 15 mg) with placebo under conditions close to those of general practice. All patients between 16 and 60 years of age, presenting an anxiety syndrome as a result of neurotic disturbance, for whom benzodiazepine treatment was indicated for at least 3 weeks, were accepted for the study. The results from 231 patients (119 on placebo, 55 on 10 mg and 57 on 15 mg diazepam) were analyzed after 1 and 3 weeks of treatment. Complaints were found to have improved after 1 week and 3 weeks in the controlled-release diazepam groups whereas the corresponding results with placebo were clearly less favourable. After 1 week, and even more strikingly after 3 weeks, evaluation of the general effects of treatment showed better results with diazepam than with placebo. The obviously higher rate of drop-outs on placebo confirmed its less reliable effect. The controlled-release capsules were well tolerated and notably better than placebo. The most frequent side-effect reported on diazepam was fatigue, and this was probably due to a relative overdosage from use of a standardized dose throughout treatment. Other reported side-effects could not definitely be ascribed to the drug. At the end of a week, successful results were achieved in 48.2% of the patients on controlled-release diazepam compared with only 14.3% of those on placebo. After 3 weeks, these figures were 73.2% and 30.3%, respectively.

Adolescent↗

Mortality among industrial workers exposed to formaldehyde.

A historical cohort study evaluated the mortality experience of 26,561 workers employed in 10 formaldehyde-producing or -using facilities. Approximately 600,000 person-years of follow-up accrued as workers were followed to January 1, 1980. Estimates of historical exposure to formaldehyde by job were developed by project industrial hygienists using monitoring data available from participating plants, comments from long-term workers, and comprehensive monitoring data specifically collected for this study. Mortality from all causes combined was about as expected [standardized mortality ratio (SMR) = 96] based on mortality rates of the general U.S. population. Significantly fewer deaths occurred from infective and parasitic diseases (SMR = 51) and from accidents (SMR = 72) than expected. Cancer overall was not related to formaldehyde exposure. Workers exposed to formaldehyde had slight excesses for Hodgkin's disease and cancers of the lung and prostate gland, but these excesses were not consistently related to duration of or average, cumulative, or peak formaldehyde exposure levels. Recent animal studies found nasal cancer among rats exposed to formaldehyde, but no excess of this tumor occurred in this study. Mortality from brain cancer and leukemia among these industrial workers was not excessive in contrast to reported excesses among professional groups (e.g., anatomists, embalmers, and pathologists) with exposure to formaldehyde. Although there was a deficit for cancer of the buccal cavity and pharynx, mortality from certain subsites, i.e., the nasopharynx and oropharynx, was elevated. These subsites did not, however, show a consistently rising risk with level of exposure. These data provide little evidence that mortality from cancer is associated with formaldehyde exposure at levels experienced by workers in this study.

Adult↗

Contagious equine metritis: experimental infection in the donkey.

Contagious equine metritis (CEM) was reproduced in 3 of 4 donkey mares with an Irish streptomycin-resistant strain of Haemophilus equigenitalis isolated from an experimental case of the disease in a pony mare. Although some variability in clinical response occurred, there was no evidence that semen enhanced the clinical severity of the infection. Variable amounts of vaginal discharge and associated inflammatory changes of the vagina and/or cervix, similar to those seen in the horse, were observed. All the affected donkeys made spontaneous clinical recoveries and so far as could be detected, subsequent persistence of H. equigenitalis in the genital tract was of limited duration. Recovery of the bacterium was not associated with oestrus and there was no evidence that it persisted in the clitoral area after it could no longer be cultured from the anterior genital tract. Cytological examination of smears of intra-uterine or cervical swabs was of diagnostic value only during the clinical phase of the infection. Serological responses demonstrated in 3 of the 4 donkey mares by the agglutination, complement-fixation and passive haemagglutination tests, were of low magnitude and short duration. The diagnostic value of the agglutination and complement-fixation tests was limited by the presence of low levels of non-specific reactivity and pronounced anti-complementary reactivity, respectively, in many of the donkey sera. The passive haemagglutination test proved superior for demonstrating elevation in antibody and for confirming infection. The overall results indicate that the donkey has the potential to act as a source of CEM infection and under certain circumstances, could have a role to play in the epidemiology of this disease.

Animals↗

The psychosexual histories of young women with bulimia.

While it is known that anorexia nervosa patients show a wide range of sexual knowledge, attitudes and practices, the psychosexual histories of bulimia patients have not been studied. In this paper the psychosexual histories of 20 bulimic patients and 20 matched control subjects are presented. Bulimic patients were more likely to experience orgasm with masturbation, were more likely to have experimented with anal intercourse, and were more likely to describe their libido as 'above average.' Control subjects were more likely to experience orgasm during sexual intercourse. Bulimic patients associated high body weights with unattractiveness, and tended to withdraw from social and sexual activity at high weights. In other aspects of their sexual behaviour, and in their attitudes to sexual matters, the two groups were similar.

Adolescent↗

Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis.

Although normal plasma ammonium levels can be maintained in children with inborn errors of ureagenesis, these children are vulnerable to episodic hyperammonemia often resulting in coma and death. To treat such episodes, we designed a therapeutic protocol that included prompt recognition of hyperammonemia, therapy with intravenous sodium benzoate, sodium phenylacetate, and arginine, and nitrogen-free intravenous alimentation. Dialysis was performed if the hyperammonemia was unresponsive to drug therapy. Twelve episodes of hyperammonemia in seven children deficient in carbamyl phosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase were treated; one patient died and the others recovered. In two patients measurement of the distribution of urinary nitrogen revealed that hippurate nitrogen and phenylacetylglutamine nitrogen together accounted for 60 per cent of "effective" urinary waste nitrogen. Successful therapy of episodic hyperammonemia plays an important part in the long-term management of disorders of the urea cycle.

Amino Acid Metabolism, Inborn Errors↗