Biomedical subjects
A Winder
Publications and source records attributed to A Winder.
Tissue specific expression of the human alpha(1-3) fucosyltransferase gene family.
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Increase in leukocyte adhesiveness and aggregation with stress: a model of human congestive heart failure.
Stress has a significant influence on the function of the human organism. A simple, rapid, inexpensive, and reliable marker for stress would therefore be of great value. We have recently noted that stress increases the state of leukocyte adhesiveness and aggregation in the peripheral blood. We evaluated 64 patients who had various degrees of congestive heart failure, a condition known to induce a state of physiologic stress, to verify whether a relation exists between the intensity of the stress response and the magnitude of leukocyte adhesiveness. Included in the 64 were 53 patients without congestive heart failure, 23 with compensated failure, 22 with significant congestive heart failure, and 19 with florid pulmonary edema. The percentage of aggregated leukocytes in these four group was 6% +/- 4%, 6% +/- 4%, 10.5% +/- 5%, and 15% +/- 14%. Values for the third and fourth group differed in a statistically significant way. Thus, with further investigation into additional stress-inducing conditions, the state of leukocyte adhesion and aggregation may prove to be a reliable marker for the detection of stress and an inexpensive tool for quantifying its severity.
Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis.
Several genes critical to the enzymatic regulation of melanin production in mammals have recently been cloned and mapped to the albino, brown and slaty loci in mice. All three genes encode proteins with similar structures and features, but with distinct catalytic capacities; the functions of two of those gene products have previously been identified. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, while the slaty locus encodes tyrosinase-related protein 2 (TRP2), an enzyme with a single specific, but distinct, function as DOPAchrome tautomerase. Although the brown locus, encoding TRP1, was actually the first member of the tyrosinase gene family to be cloned, its catalytic function (which results in the production of black rather than brown melanin) has been in general dispute. In this study we have used two different techniques (expression of TRP1 in transfected fibroblasts and immunoaffinity purification of TRP1 from melanocytes) to examine the enzymatic function(s) of TRP1. The data demonstrate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indole-quinone at a down-stream point in the melanin biosynthetic pathway. This enzyme activity appears to be essential to the further metabolism of DHICA to a high molecular weight pigmented biopolymer.
Lipoprotein lipase activity in patients with combined hyperlipidaemia.
The aetiology of familial combined hyperlipidaemia remains obscure, with both genetic and environmental factors contributing to the phenotype, which is frequently associated with premature coronary heart disease. We have studied lipoprotein lipase (LPL) activity and hepatic lipase (HL) activity in patients with coronary heart disease to determine whether variation in lipase activities contributes to this phenotype. Forty-one patients (mean age 50 years; 30 male) were selected on the basis of cholesterol levels above 6.5 mmol/l and triglyceride levels above 2.2 mmol/l, with apoprotein B values over the 90th percentile. There was a family history of premature coronary heart disease in 78% and a personal history in 64%, at mean age 44, the patient group therefore predominantly corresponded to the common definition of familial combined hyperlipidaemia, appropriate in the absence of molecular markers. None of the patients was diabetic; hypertension and smoking were not over represented. Blood samples were taken following intravenous administration of heparin (100 IU/kg body wt), and LPL and HL activities were measured. Mean post-heparin LPL was significantly lower in patients than controls 10 min after heparin administration (2.98 +/- 1.04 and 3.86 +/- 0.93 mumol ml-1 h-1, respectively, P = 0.001), and 37% patients had values below the 10th percentile of controls. Both male and female patients had significantly higher HL activities than their respective controls at 5, 10, 20 and 30 minutes post-heparin. As expected, both female patients and controls had lower HL activities than males, although this sex difference did not reach statistical significance in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)
DHICA oxidase activity of TRP1 and interactions with other melanogenic enzymes.
Tyrosinase-related protein 1 (TRP1) maps to the brown locus in mice. Although the specific function of TRP1 has been in dispute, mutations in its structural gene result in the formation of brown rather than black melanin. We have investigated the melanogenic function of TRP1 by using immune-affinity purification of the protein and also by using transfection of its gene into fibroblasts to study its characteristics. We show that TRP1 has the ability to oxidize DHICA, a melanogenic intermediate derived from DOPAchrome. In addition, TRP1 has the ability to interact with tyrosinase and significantly stabilize the latter's catalytic function.
The tyrosinase gene family--interactions of melanogenic proteins to regulate melanogenesis.
Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, the brown locus encodes TRP1 (tyrosinase-related protein-1), and the slaty locus encodes TRP2, another tyrosinase related-protein. TRP2 functions as DOPAchrome tautomerase, an enzyme that preserves the carboxylic acid content of melanins, which would be spontaneously lost in its absence, while TRP1 is able to oxidize the DHICA produced by TRP2. In this study we have used three different systems (immune-affinity purified melanogenic enzymes, mutant melanocytes, and transfected cells) to examine the enzymatic interactions of these proteins, and their stabilization in a complex which significantly increases their physiological half-life. When extrapolated to the melanocyte, our results demonstrate the catalytic functions of these proteins and suggest how they might stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized.
A combined urodynamic and continence unit--a review of the first 19 years.
We have completed a 19-year audit of all patients referred to the urodynamic/continence unit since its inception in 1972 and their subsequent clinical management; a total of 20,437 patients were referred, increasing from 51 in the first year to 1564 in 1990. Although the annual number of referrals has remained constant for the last 8 years, the need for more complex urodynamic assessment such as video-cystourethrography has increased from 5% (56/1164) in 1981 to 25% (385/1564) in 1990. The number of out-patient attendances to medical, physiotherapy and continence clinics has also increased over that period. We conclude that the number of referrals represents increasing recognition of the value of urodynamic assessment. Accurate diagnosis leads to more effective treatment, whether surgical, medical or conservative. Some methods of diagnosis are complex and suitable only for a tertiary referral centre.
Acetazolamide-responsive vestibulocerebellar syndrome: clinical and oculographic features.
Five patients who presented with long-standing episodic vertigo had ocular motor signs localizing to the vestibulocerebellum. In each patient, the episodic vertigo was either abolished or markedly decreased in frequency and severity with acetazolamide therapy. In 4, other family members had identical symptoms and signs. This syndrome is 1 of the few treatable causes of chronic episodic vertigo.
The persistence of neutralizing antibodies after revaccination against smallpox.
Persistence of neutralizing antibodies after revaccination against smallpox was studied. Single serum samples from 140 revaccinated donors were tested for neutralizing antibodies using the plaque reduction assay. The donors, aged 21-49 years at sampling, had been vaccinated in infancy and revaccinated at 8 and 18 years; they formed seven groups of 20 men each, revaccinated about 3, 5, 10, 15, 20, 25, and 30 years before sampling. The differences in mean titer among groups were insignificant (P greater than .01). The titer significantly decreased during the first 3 years after the revaccination but remained stable for at least 30 years thereafter (geometric mean titer, 10.5; 95% confidence interval, 6.8-16.4). The results suggest that there is probably no need for routine revaccinations beyond the primary and two revaccinations; nevertheless, persons at high risk should be revaccinated regardless of their vaccination status.
Intermittent self-catheterisation.
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Serum gamma-aminobutyric acid (GABA) levels in patients with hepatic encephalopathy.
Serum levels of the potent inhibitory neurotransmitter gamma aminobutyric acid (GABA) were measured in 10 patients with chronic liver disease and hepatic encephalopathy, 11 patients with chronic liver disease and no evidence of hepatic encephalopathy, 7 patients with end-stage renal disease and 11 healthy volunteers. Serum GABA levels were elevated in all 10 patients with hepatic encephalopathy, 5/11 with liver disease and no encephalopathy and 4/7 renal disease patients. The mean serum GABA level for the encephalopathic patients (0.92 +/- 0.13 microM, mean +/- SEM) was significantly greater than the mean for liver disease patients without encephalopathy (0.48 +/- 0.05 microM, p less than 0.05), renal disease patients (0.46 +/- 0.04 microM, p less than 0.05) and healthy volunteers (0.39 +/- 0.03 microM, p less than 0.001). These results would tend to support the hypothesis that GABA may play a role in the pathogenesis of hepatic encephalopathy.
Intermittent self-catheterisation.
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Catheters. Achieving independence.
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Continence. Target practice.
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