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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 289 records · Page 16Linked to original sources

Androgen resistance syndromes.

Hereditary defects that impede androgen action cause resistance to the hormone both during embryogenesis and in later life and hence usually cause developmental defects of the male urogenital tract. In genetic males such defects produce a phenotypic spectrum ranging from infertile but otherwise normal men to individuals with varying degrees of ambiguous genitalia to phenotypic women. These disorders can be classified on the basis of the step in androgen action that is impeded by the individual mutations. 5 alpha-Reductase deficiency is an autosomal recessive enzyme defect that impairs the conversion of testosterone to dihydrotestosterone. The internal male genital tract virilizes normally, but the external genitalia are predominantly female in character. The syndrome is the result of one of several mutations that impair the function of the 5 alpha-reductase enzyme. A variety of disorders influence the androgen receptor that mediates the action of both testosterone and dihydrotestosterone. At least four phenotypic variants can be distinguished: complete testicular feminization, incomplete testicular feminization, the Reifenstein syndrome, and the infertile male syndrome, each of which is inherited as an X-linked trait. Absence of receptor binding is found commonly in complete testicular feminization, but qualitative and/or less severe quantitative defects in receptor function can be associated with all four variants. A third type of disorder, receptor positive resistance, also causes variable defects in male development and is associated with normal 5 alpha-reductase activity and normal androgen receptor. The underlying defect is presumed to lie at the intranuclear site or sites of action of the hormone-receptor complex.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Deposition of sidestream cigarette smoke in the human respiratory tract.

Measurement of deposition of sidestream cigarette smoke in the human respiratory tract is important for assessing the health effects of sidestream cigarette smoke. We measured the deposition fraction of sidestream cigarette smoke in 5 normal adult male volunteers using sidestream smoke at a concentration similar to that encountered indoors with smokers present. The mean deposition was 11%. These data indicate that the deposition fraction of sidestream smoke is similar to other previously studied aerosols in the same size range and is much less than mainstream smoke.

Adult↗

Developmental pattern of increased aromatase activity in the Sebright bantam chicken.

Feathers in the male Sebright bantam chicken are feminized as the result of a mutation that causes an increase in the capacity for estrogen synthesis (aromatase activity) in skin. To determine when during development the increased aromatase activity is expressed, we measured the enzyme in tissue slices of Sebright bantam and control bantam chickens of days 3, 12, and 18 of embryogenesis, on day 1 after hatching, and in mature birds. An assay was used that measures the release of 3H2O from [1 beta-3H]testosterone during the aromatization process. Aromatase activity was expressed in the 3-day-old Sebright embryos, but was not detectable in control embryos of the same age. In older embryos and birds, aromatase activity was assayed in multiple tissues. Enzyme activity was detectable in all tissues examined from day 12 and day 18 Sebright embryos. In control embryos, aromatase was detectable in ovarian but not in extraglandular tissues. The enzyme activity in most tissues of the Sebright decreased within 1 day after hatching and continued to decrease thereafter so that in the adult Sebright, aromatase activity was high only in skin (and skin appendages) and ovary. We conclude that the normal allele of this gene acts to limit the rate of estrogen formation in extraglandular tissues.

Aging↗

Rheumatic fever and smooth muscle antibodies.

Rheumatic fever is a nonsuppurative sequelae to Group A streptococcal pharyngitis. Valvulitis resulting from cardiac involvement in this disease, is the main cause of morbidity in rheumatic fever. The study of rheumatic fever sera on cryostat sections of a variety of tissues using indirect immunofluorescence is described. A 95% incidence of smooth muscle antibody was found in 236 rheumatic fever sera, from 55 patients. Sera from hospital patients with a variety of diseases had an overall incidence of 12% for smooth muscle antibodies. The pattern and distribution of tissue staining strongly suggests that the smooth muscle antibodies described in rheumatic fever sera have antiactin specificity. This finding raises many questions concerning the immunopathogenesis and immunogenetics of rheumatic fever, and the pathogenesis of a number of diseases in which streptococci have not previously been considered.

Actins↗

Azatadine maleate (Zadine): evaluation in the management of allergic rhinitis.

Azatadine maleate (Zadine), a new antihistamine, was evaluated for its efficacy in 20 patients with chronic allergic rhinitis. Eighty percent of patients had symptomatic relief with a twice daily dosage of 2 mg. Sedation was volunteered as a side effect by six of the patients and was admitted by two further patients after specific questioning. A choice reaction time test gave slowing of motor function in these sedated patients. Four of the previously sedated patients experienced good symptomatic control with minimal sedation when the azatadine dose was reduced to 1 mg twice daily; slowing of motor function was not observed at this, the normal recommended dose.

Adolescent↗

Variation in potency of extracts used for allergy skin tests.

Extracts of 11 common inhalant allergens, produced by three different commercial suppliers, were compared by the skin prick test (SPT) in 21 atopic subjects. Good correlation was found between the three brands for positive reactions to grass pollens and English plantain pollen. Eighteen subjects with clinical sensitivity to house dust had diagnostically positive reactions to two of the house dust mite extracts, the third preparation produced no reactions that would be considered as diagnostically significant by the usual criteria. The extracts of house dust mixtures possessed little biological activity and were considered unsatisfactory for accurate diagnostic purposes. One of the three extracts of dog hair and dander produced false positive results in 17 of 21 subjects. The variability of reactions to fungi and animal hair and dander is discussed.

Adult↗

Has the change to beta-agonists combined with oral theophylline increased cases of fatal asthma?

An apparent increase in young people dying suddenly from acute asthma has been noted in the past 2 years in Auckland. 22 fatal cases were reviewed. Prescribing habits for asthma therapy have been changing in New Zealand, with a considerable increase in the use of oral theophylline drugs, particularly sustained-release preparations, which in many patients have replaced inhaled steroids and cromoglycate. It is suggested that there may be an additive toxicity between theophylline and inhaled beta 2-agonists at high doses which produces cardiac arrest. Also when regular symptomatic treatment with bronchodilators replaces inhaled steroids or cromoglycate the patient's perception of an asthma crisis may be delayed.

Administration, Oral↗

Increased estrogen formation and aromatase activity in fibroblasts cultured from the skin of chickens with the Henny feathering trait.

The henny feathering trait in chickens leads to a marked increase in the conversion of androgen to estrogen in skin and other peripheral tissues with the result that feathers of affected males are feminized. To gain insight into the mechanisms responsible for this increased estrogen synthesis, we studied the conversion of testosterone to estrogen in fibroblasts cultured from the skin of control chickens and from two breeds carrying the henny feathering trait, the Sebright bantam and the Campine. Estrogen synthesis was measured in suspensions of intact fibroblasts and in cell-free fibroblast extracts by two assays: 1) direct measurement of 17 beta-estradiol formation from [1,2,6,7-3H]testosterone, and 2) assessment of 3H2O release from [1 beta-3H]testosterone. Both assays gave comparable results. Estrogen formation was as much as several hundred-fold higher in fibroblasts cultured from skin of chickens carrying the henny feathering trait compared to that observed in fibroblasts from skin of control chickens. The current data indicate that increased estrogen formation in skin of chickens with the henny feathering trait is due to an enhanced activity of the aromatase complex of enzymes responsible for estrogen synthesis. The molecular basis for this increased activity is unclear.

Animals↗

Variation in steroid 5 alpha-reductase activity in cloned human skin fibroblasts. Shift in phenotypic expression from high to low activity upon subcloning.

Steroid 5 alpha-reductase in skin fibroblasts varies in two ways: 1) mean activity in uncloned fibroblasts corresponds to the activity in skin from which fibroblasts are derived (high in genital skin and low in nongenital skin); 2) activity in normal genital skin fibroblasts varies over a wide range (more than 200-fold). Studies of activity in fibroblast clones provides an explanation for this variability. Activity in clones of genital skin fibroblasts varies from the limits of detectability to very high levels, whereas activity in fibroblasts cloned from nongenital skin is uniformly low. The mean value of 5 alpha-reductase in genital skin clones is similar to the value in uncloned fibroblasts from the same explant. This suggests that the numbers of high and low activity cells in a given explant influence the overall enzyme activity. Variability among normal genital skin strains is also due to inherent differences in the range of enzyme activities. Furthermore, high activity genital skin clones give rise to a mixture of both high and low-activity subclones, whereas low activity genital skin and nongenital skin clones give rise to populations with uniformly low activity. Thus, with time genital skin gives rise to high activity fibroblasts that continually undergo shift in phenotypic expression to low activity.

17-Hydroxysteroid Dehydrogenases↗

Allergic sensitivity confirmed by the release of histamine from small blood samples.

An enzymatic-isotopic microassay that can measure picogram amounts of histamine in 20 microliter samples of plasma has been used to confirm diagnosis of allergic sensitivity to extracts of house dust mite, cat dander, grass, plantain, Cladosporium mould and bee sting venom by the skin test procedure. Multiple assays for allergic histamine release can be performed on minimal blood samples resulting in a qualitative and quantitative prediction of allergic sensitivity from an in vitro biochemical procedure.

Animals↗

Role of gonadal hormones in development of the sexual phenotypes.

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 fetal testis, Müllerian inhibiting substance and testosterone, are responsible for male development. Studies of single gene mutations that interfere with androgen action indicate that testosterone itself is responsible for virilization of the Wolffian duct system into the epididymis, vas deferens, and seminal vesicle, whereas the testosterone metabolite dihydrotestosterone induces development of the prostate and male external genitalia. Thus, impairment of dihydrotestosterone formation results in a characteristics phenotype consisting of predominantly female external genitalia but normally virilized Wolffian ducts. The molecular mechanisms by which testosterone and dihydrotestosterone act during fetal 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.

Anti-Mullerian Hormone↗

Genetic and endocrine control of renin activity in the submaxillary gland of the mouse.

Basal activity of submaxillary gland (SMG) renin is high in female mice that carry the Rnrs allele and is induced to higher levels by treatment with dihydrotestosterone (DHT). To determine whether the difference in basal activity between high (Rnrs/Rnrs) and low (Rnrb/Rnrb) strains is due to enhanced sensitivity of Rnrs/Rnrs strains to endogenous androgen, we first studied the effect of several types of endocrine ablation on SMG renin in young female mice, and second, we removed normal androgen receptor protein by introducing the X-linked Tfm gene. Adrenalectomy with or without castration had no effect on basal SMG renin; hypophysectomy decreased basal renin activity 400-fold but did not abolish responsiveness to DHT. Loss of androgen receptor did not affect basal renin activity but did prevent enhancement by DHT. Basal and induced renin activities in L.AKR(Alll)/Cy, a congenic strain homozygous for Rnrs introduced from AKR/J into the background of C57L/J, an Rnrb/Rnrb type strain, are intermediate between levels observed in the original strains. We conclude that (1) the basal level of SMG renin is regulated directly or indirectly by some pituitary hormone(s) but not by androgen, (2) androgen induction of renin activity requires a normal androgen receptor, and (3) major gene(s) that regulate basal as well as induced SMG renin are in a circumscribed region of chromosome 1.

Adrenalectomy↗