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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 271 records · Page 15Linked to original sources
PubMed1983

Anaphylactoid reactions to neuromuscular blocking agents: a commonly undiagnosed condition?

A group of 28 patients with extreme, life-threatening sensitivity to suxamethonium was identified and 15 were studied in detail by skin-testing. The female/male ratio was 8/1. Sensitivity may be present without previous exposure to suxamethonium; in 3 patients reactions occurred during the first exposure to anaesthesia. Most patients showed one or more cross-sensitivities to alcuronium, tubocurarine, and gallamine. Signs of circulatory collapse were the sole presenting feature in 50% of the patients. Histamine release induced by the drug in vitro was demonstrated in some instances.

Alcuronium↗
PubMed1983

Suprasellar germinoma. Unresolved problems in diagnosis, pathogenesis, and management.

A suprasellar germinoma, initially thought to be granulomatous diencephalitis of uncertain cause, responded following chloramphenicol and methicillin treatment both by clinical and radiographic criteria and was not diagnosed until a third biopsy was performed. Analysis of this case and review of the literature lead to the conclusion that adequate diagnostic workup of such lesions requires that biopsy be extensive enough to include the central core as well as the granulomatous reaction that surrounds such tumors. Furthermore, since the degree of inflammation may fluctuate, regression does not mean that the lesion is not neoplastic in origin. In the present instance, the correct diagnosis could have been made earlier if the beta-chain of human chorionic gonadotropin had been measured in spinal fluid.

Adult↗
PubMed1983

Characterization of the increased estrogen synthesis in skin fibroblasts from the Sebright bantam.

We have utilized the Sebright bantam chicken as a model system to explore the regulation of estrogen formation in peripheral tissues. As the result of a gene mutation, Sebright males develop a female feathering pattern associated with an increase in estrogen synthesis in skin and in fibroblasts cultured from skin. To provide insight into the mechanisms by which estrogen synthesis is increased we examined several parameters of the aromatase reaction in homogenates from control ovaries, Sebright ovaries and fibroblasts grown from Sebright skin: the pH optima; the apparent Km's for testosterone, 19-nortestosterone, androstenedione, 16-hydroxyandrostenedione, and NADPH; the apparent Ki's for 4-hydroxyandrostenedione, aminoglutethimide, dehydroepiandrosterone, and 19-hydroxytestosterone; and the inactivation of the reaction by heating. No qualitative differences were identified in the enzyme from Sebright and control birds.

Androstenedione↗
PubMed1983

The endocrine control of male phenotypic development.

Male and female embryos develop in an identical fashion during the initial portion of gestation. If the indifferent gonad differentiates into an ovary (or if no gonad is present), a female phenotype is formed. Male phenotypic differentiation, however, requires the presence of an endocrinologically active testis. Two secretions of the foetal testis, Mullerian-inhibiting substance and testosterone, are responsible for male development. Testosterone itself is responsible for virilization of the Wolffian duct system into the epididymis, vas deferens, and seminal vesicle, whereas dihydrotestosterone induces development of the prostate and male external genitalia. Thus, impairment of dihydrotestosterone formation results in a characteristic phenotype consisting of predominantly female external genitalia but normally virilized Wolffian ducts. The molecular mechanisms by which testosterone and dihydrotestosterone act during foetal development appear to involve the same high affinity receptor, a protein that transports both testosterone and dihydrotestosterone to the nucleus of target cells. When this receptor is either absent, deficient, or structurally abnormal, the actions of both testosterone and dihydrotestosterone are impaired, and the resulting developmental anomalies involve both internal and external genital structures.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Granulosa cell differentiation and estrogen synthesis in the fetal rabbit ovary.

Morphologic development of the granulosa cell and the capacity for estrogen biosynthesis were evaluated in ovaries from New Zealand white rabbit fetuses at 16, 17, 18, 19, 20, 24 and 28 days of gestation. By light microscopy, granulosa cells within the developing cortical cords showed extensive accumulation of lipid material in their cytoplasm at Days 18, 19 and 20. Electron microscopy confirmed the presence of abundant lipid in granulosa cells at these times and showed that lipid is present in cytoplasmic droplets, often in coalescent aggregates. Quantitative morphometric examination demonstrated a sixfold increase in lipid between Days 16 and 19 and a subsequent decrease to earlier values by Day 24. In parallel studies, estrogen formation from [1 beta-3H]testosterone was low in Days 17 and 18 ovaries, increased approximately sixfold by Day 20 and fell by Day 24. Thus, the capacity of granulosa cells of the fetal ovary to form estradiol correlates with their cytoplasmic lipid content.

Animals↗
PubMed1983

Astemizole: a new long-acting antihistamine in the treatment of seasonal allergic rhinitis.

Astemizole, a new long-acting antihistamine, (H1 receptor antagonist), 10 mg taken once daily was found to be an effective prophylactic treatment for the symptoms of allergic rhinitis in 75% (twelve from sixteen) of subjects in a double-blind placebo-controlled study. The success rate with placebo was less than 20% (three from sixteen). There were two treatment failures in highly atopic individuals taking the active drug. The classic side effects of antihistamines, most notably sedation, were minimal and reflected in the control group. Two subjects reported weight gain: one of these noted an increase in appetite during the 6-week trial period. Six of seven subjects who continued to take the drug for a longer period (up to 16 weeks) experienced marked weight gain: five of them reported an increase in appetite. Reactions to allergen skin tests were significantly reduced in patients taking astemizole.

Adolescent↗
PubMed1983

Pregnancy complicated by an insulinoma.

The case of a 33-year-old patient suffering from severe hypoglycaemia due to an insulinoma during the first trimester of pregnancy is reported. The diagnosis was established on clinical grounds and by the demonstration of hypoglycaemia, inappropriate hyperinsulinism and an increase in the percentage of circulating proinsulin. Dietary therapy maintained blood glucose at a satisfactory level from the 9th to the 17th gestational week. Localization of the tumour was achieved at that time by limited CT scanning with a narrow field. A 2 cm tumour was removed from the head of the pancreas and the blood sugar levels and insulin secretion returned to normal. Pregnancy proceeded normally and a healthy male infant weighing 3,880g was delivered at term. Ten months after delivery both mother and child were well.

Adenoma, Islet Cell↗
PubMed1983

Membrane-bound fractions of R6K plasmid DNA in Escherichia coli.

The intracellular location of plasmid DNA has been of interest in an effort to understand the maintenance of these molecules. We have employed a simple procedure which enables us to isolate from exponentially grown cells on sucrose gradients membrane-complexed forms of R6K plasmid DNA. Electron micrographs identified the complexing of membrane fractions to circular forms of R6K DNA. Biochemical studies of the complexed R6K molecules showed the presence of membrane-specific proteins and suggested that complexing of R6K DNA was primarily with inner membrane fractions of Escherichia coli.

Bacterial Proteins↗
PubMed1983

The effect of a 5 alpha-reductase inhibitor on androgen-mediated growth of the dog prostate.

The administration of testosterone cypionate (0.4 mg/kg BW . day) to castrated male dogs caused a doubling of prostate weight within 4 weeks and an increase in the content of testosterone and dihydrotestosterone in the prostate. When the 5 alpha-reductase inhibitor 17-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (3 mg/kg BW . day) was administered simultaneously with testosterone cypionate, prostatic testosterone content increased from 0.5 +/- 0.2 to 4.1 +/- 1.3 ng/mg DNA, the increase in prostatic dihydrotestosterone content was prevented, and prostatic size decreased to half the starting weight. These results suggest that dihydrotestosterone formation plays a role in prostatic growth.

5-alpha Reductase Inhibitors↗
PubMed1983

Transformation of human androgen receptors to the deoxyribonucleic acid-binding state.

The transformation of [3H]dihydrotestosterone-androgen receptor complexes to the nuclear binding state was studied in fibroblasts cultured from human genital skin, using binding of the androgen-receptor complex to DNA-cellulose as a measure of transformation. Transformation of cytosolic dihydrotestosterone-receptor complexes proceeded slowly at 0 C, and heating to 25 C caused rapid transformation that was essentially complete within 15 min. Sodium molybdate (up to 10 mM) slowed the rate of transformation in a concentration-dependent fashion; low concentrations of molybdate (0.5-1 mM) prevented transformation at 0 C, but transformation of up to 70% of the total cytosolic hormone-receptor complexes could be achieved in the presence of high concentrations of molybdate by appropriately prolonged heating at 25 C. Molybdate appeared to exhibit a dual effect, increasing the total amount of androgen-receptor complex recoverable in cytosol and prolonging the time course of heat-induced transformation. Treatment of cytosolic dihydrotestosterone-receptor complexes with 0.5 M NaCl caused a degree of transformation similar to that seen after heat treatment but was unaffected by 10 mM molybdate. Transformation was accompanied by disappearance of the 7S form of the receptor on sucrose density gradients, but there was no reciprocal increase in a smaller size binding moiety on low ionic strength sucrose density gradients. The heat-transformed receptor could be detected, however, as a 3S binding peak on gradients containing 0.3 M NaCl, suggesting that transformation was accompanied by a structural alteration of the hormone-receptor complex.

Cellulose↗
PubMed1983

Characterization of the cytosol androgen receptor of the human prostate.

Direct measurement of the binding of endogenous androgens to the androgen receptor of human tissues has not been possible because of contamination of tissue with traces of plasma proteins, such as testosterone-binding globulin (TeBG), that contain more androgen-binding capacity than does the receptor itself. Molybdate is known to stabilize the 8-9S forms of other steroid hormone receptors. We took advantage of this phenomenon to characterize the androgen receptor of hyperplastic prostates removed at surgery, using sucrose density gradient centrifugation in a vertical rotor. In 10 mM sodium molybdate, the androgen receptor sediments as a distinct 9.2 +/- 0.5S moiety, easily separable from TeBG. Unlike TeBG, the 9S receptor is not removed by absorption with Concanavalin A. [3H]Dihydrotestosterone (3H-labeled 17 beta-hydroxy-5-alpha-androstan-3-one) binding to the 9S receptor is not removed by absorption with Concanavalin A. [3H]Dihydrotestosterone (3H-labeled 17 beta-hydroxy-5 alpha-androstan-3-one) binding to the 9S receptor is not competed for by excess triamcinolone acetonide (9 alpha-fluoro-11 beta, 16 alpha, 17 alpha, 21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetonide) or promegestone (17,21-dimethyl-19-non-pregna-4,9-diene-3,-20-dione), which are known to bind to the progestin receptor. In contrast, [3H]methyltrienolone (3H-labeled 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one) binds to both androgen and progestin receptors, and consequently, the binding of this ligand to the androgen receptor was assessed in the presence of a 500-fold excess of triamcinolone acetonide. The amounts of 9S binding (7.8 and 5.8 fmol/mg protein) are similar for dihydrotestosterone and methyltrienolone. The amount of 9S binding of testosterone to the receptor was also similar to that of dihydrotestosterone, but the affinity of testosterone for the 9S receptor was only a fifth or less of that for dihydrotestosterone. The observation that testosterone binds less avidly than dihydrotestosterone to the receptor may explain the role of dihydrotestosterone formation in androgen physiology.

Centrifugation, Density Gradient↗
PubMed1983

Cerebrospinal fluid rhinorrhoea during treatment of pituitary tumours with bromocriptine.

Bromocriptine is widely used in the treatment of hyperprolactinaemia. It has also been shown to be effective in reducing the size of large pituitary tumours, particularly those secreting prolactin. We describe CSF rhinorrhoea in two such patients during treatment with bromocriptine and believe that this complication developed as a result of contraction of the tumour exposing a defect in the sella floor. The possibility of this complication, especially in patients with downward extension of tumour, should be noted.

Adult↗
PubMed1983

Ovulation induction with pulsatile gonadotrophin releasing hormone (GnRH).

Anovulatory infertility has been successfully treated in 7 out of 13 women by means of pulsatile gonadotrophin releasing hormone (GnRH) therapy. Women with primary or secondary amenorrhoea received a bolus of GnRH (2.1-20 micrograms) subcutaneously once every 60, 90 or 120 min around the clock from a programmable, battery operated, syringe driver worn under the clothing. Duration of treatment varied from 1 week to 8 months (mean 2.5 months); 7 women ovulated and 2 conceived in the first month of treatment. We conclude that anovulatory women with normal prolactin levels, who are refractory to clomiphene with or without HCG, and who are unlikely to respond to anything but human pituitary FSH and HCG may now be treated with GnRH.

Adult↗
PubMed1983

Expression of a mutant androgen receptor in cloned fibroblasts derived from a heterozygous carrier for the syndrome of testicular feminization.

Thermolability of androgen binding was compared in fibroblasts cloned from normal female skin, skin from a subject with testicular feminization whose mutation is known to be associated with a thermolabile androgen receptor, and from the mother of the subject with testicular feminization. Seven of 28 clones studied from the mother exhibited thermolability of binding, indicating that the mutant gene that causes thermolability of binding, like the gene responsible for the normal androgen receptor, is X-linked.

Adolescent↗
PubMed1982

Inhibition of steroid 5 alpha-reductase from human skin fibroblasts by 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one.

The capacity of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (DMAA) to inhibit competitively steroid 5 alpha-reductase has been confirmed in human foreskin fibroblasts. The inhibitor works equally well in homogenates and in intact cells, is rapidly reversible, does not influence the amount of the enzyme, is equally effective in inhibiting the 5 alpha-reduction of testosterone, 4-androstene-3,17-dione, 20 alpha-hydroxy-4-pregnen-3-one and cortisol, and appears to be weakly bound to serum protein. The inhibitor is particularly effective (apparent Ki of approximately 3 nM) at the optimal pH of the enzyme (pH 5.5) and has no effect in the alkaline range (pH 9.0). DMAA appears to be a steroid that will be useful in the investigation of 5 alpha-reduction of steroid hormones in intact animals and in embryos.

17-Hydroxysteroid Dehydrogenases↗
PubMed1982

Beta-adrenergic-receptor blockers and antinuclear antibodies in hypertension.

It has recently been reported that the Beta-adrenergic receptor-blocker acebutolol accelerates the development of antinuclear antibodies (ANAs) in hypertensive patients. We examined data from over 1500 hypertensive patients to determine whether this effect is associated with other beta blockers. Groups of patients treated with acebutolol, atenolol, labetalol, and pindolol all displayed increased development of ANAs relative to patients on other medication. When patients taking methyldopa (a drug associated with a high ANA incidence) were excluded from the analysis, only acebutolol retained an association (P less than 0.001) with ANA production. Sequential studies to assess the development of ANAs in patients during the course of beta-blocker treatment revealed a similar pattern. With methyldopa patients excluded, the fraction of patients developing ANAs was less then 10% for all but atenolol (10.9%), labetalol (13.8%), and acebutolol (33%). Thus, although some of the beta blockers may be associated with an increase in ANA incidence, the dramatic effects of acebutolol do not appear to be a group property.

Adrenergic beta-Antagonists↗