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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 253 records · Page 14Linked to original sources
PubMed1985

Fungal allergy and respiratory disease.

An aerobiological study of three different localities of the Auckland region using Burkard volumetric spore traps was conducted for a 12 month period from September 1979 to August 1980. High counts were recorded of various types of fungal spores of both unknown and recognised potential allergens but the basidiospore group was dominant at all sites forming greater than 50% of the total air spora. Seasonal periodicities as well as regional variations in spore concentrations of five generic group viz Ganoderma, Leptosphaeria, Cladosporium, Alternaria and Aspergillus-Penicilium were recorded. These exhibited summer and/or autumn peaks. The diel periodicities recorded for Ganoderma and Leptosphaeria were of nocturnal type. Cladosporium was diurnal and Aspergillus-Penicillium did not display any clear periodicity. The hospital admissions of acute asthma sufferers were recorded for the period January 1979 to December 1980. The seasonal pattern of airborne basidiospores of the region and the pattern of acute asthma admissions indicate a close relationship between the two.

Acute Disease↗
PubMed1985

Pancreatic islet allograft function in nonimmunosuppressed conscious mice.

CBA/H (H-2k) male mice were made diabetic by giving Streptozotocin 300 mg/kg intravenously. They were transplanted beneath the renal capsule with seven clusters of BALB/c (H-2d) adult islets, cultured for seven days in 95% O2 and 5% CO2. Basal blood glucose and weight gain returned to normal within 7 to 10 days. Blood glucose and serum insulin responses to intragastric glucose, intraperitoneal arginine and intraperitoneal theophylline were assessed after restoration of normoglycemia and compared with the responses in a control group of CBA mice. The animals were pretreated with intraperitoneal phentolamine and propranolol to reduce the stress of these procedures. Essentially normal carbohydrate tolerance was maintained in the transplanted animals but the insulin responses were markedly reduced, suggesting an increased sensitivity to insulin. The insulin content of the grafted tissue was also found to be considerably lower than that in the normal pancreas. This study demonstrates that in the mouse, adult pancreatic islet allografts can respond to stimuli that require functional adaptation by the islets. Further studies are required in larger animals before islet transplantation can be applied to the management of insulin dependent diabetic patients.

Animals↗
PubMed1985

Comparison of several control standard endotoxins to the National Reference Standard Endotoxin--an HIMA collaborative study.

A collaborative study, initiated under the auspices of the Health Industry Manufacturers Association (HIMA), was designed to establish the relationship of Escherichia coli O55:B5 endotoxin (the control standard endotoxin of HIMA and the Food and Drug Administration's Office of Medical Devices) to the U.S. National Reference Standard Endotoxin and to two internationally used control standard endotoxins. By using two Limulus amoebocyte lysate test systems, it was established that the E. coli O55:B5 endotoxin lot originally used by HIMA and the Office of Medical Devices to establish Limulus amoebocyte lysate release test criteria for pyrogen testing of medical devices contains approximately 4.5 endotoxin units (EU) per ng. Thus, the 1.0-ng/kg endotoxin dose limit currently established for medical devices is approximately the same as the 5.0-EU/kg endotoxin limit (on an activity basis) established by several other Food and Drug Administration agencies for human and animal parenteral drugs and biological products.

Endotoxins↗
PubMed1985

Quantitative deposition of ultrafine stable particles in the human respiratory tract.

Theoretical models of particle deposition in the respiratory tract predict high fractional deposition for particles of less than 0.1 micron, but there are few confirming experimental data for those predictions. We have measured the deposition fraction of a nonhygroscopic aerosol in the human respiratory tract. The aerosol had a count mean diameter of 0.044 micron SD of 1.93, as measured with an electrical aerosol analyzer, and was produced from a 0.01% solution of bis(2-ethylhexyl) sebacate using a condensation generator. Subjects inhaled the aerosol using a controlled respiratory pattern of 1 liter tidal volume, 12/min. Deposition was calculated as the difference in concentration between inhaled and exhaled aerosol of five size fractions corrected for system deposition and dead-space constants. Three deposition studies were done on each of five normal male volunteers. Means (+/- SE) for the five size fractions were 0.024 micron, 0.71 +/- 0.06; 0.043 micron, 0.62 +/- 0.06; 0.075 micron, 0.53 +/- 0.05; 0.13 micron, 0.44 +/- 0.04; and 0.24 micron, 0.37 +/- 0.06. These data demonstrate that deposition of inhaled particles in the 0.024- to 0.24-micron size range is high and increases with decreasing size. These observations agree with and validate predictions of mathematical models.

Adult↗
PubMed1985

The synthesis and metabolism of gonadal steroids in pouch young of the opossum, Didelphis virginiana.

We have measured steroid hormone biosynthesis from pregnenolone in ovaries and testes, aromatization of testosterone in gonads and peripheral tissues, and 5 alpha-reduction of testosterone in peripheral tissues of developing opossum pouch young. Sex of the newborn opossums is discernible grossly with development of the pouch in females and the scrotum in males approximately 10 days after birth. Differentiated endocrine function of ovaries and testes was demonstrable as soon as development of the pouch or scrotum was apparent. The testes synthesized testosterone, and ovaries aromatized androgens to estrogens as assessed by the conversion of [1 beta-3H] testosterone to 3H2O. This endocrine differentiation of the gonads occurs days or weeks before differentiation of the male and female urogenital tracts. As in other species, 5 alpha-reduction of [1 beta-3H] testosterone was high in urogenital sinus and urogenital tubercle. However, 5 alpha-reductase activity was highest in mesonephros and structures derived from the mesonephros. In wolffian and mullerian ducts of pouch young less than 10 days old, 5 alpha-reductase activity was greater than 50 pmol/h . mg protein and decreased by 19 days of age to approximately 3 pmol/h . mg protein, a pattern different than in eutherian mammals in which testosterone itself appears to mediate virilization of the wolffian ducts. These studies provide the framework for studies of the endocrine control of phenotypic sexual differentiation in the opossum.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1985

The interaction of androgen and thyroid hormones in the submandibular gland of the genetically hypothyroid (hyt/hyt) mouse.

The development and maintenance of granular convoluted tubule cells in the mouse submandibular gland (SMG) and the production of renin-1, renin-2, and epidermal growth factor (EGF) by these cells are under complex hormonal control. Hypophysectomy causes profound involution and loss of renin activity in this gland. We have shown previously that T4 acts synergistically with 5 alpha-dihydrotestosterone (DHT) to restore SMG morphology and renin-2 activity in hypophysectomized female mice. Investigating the mechanism of T4 and DHT interaction in the hypophysectomized mouse proved impractical, and in the present study we have used genetically hypothyroid (hyt/hyt) mice that carry the structural gene for renin-1 but not for renin-2. Levels of SMG renin-1 and EGF in hyt/hyt mice were less than 4% of those in euthyroid (hyt/+) littermates. Administration of a pharmacological dose of T4 (2.5 micrograms/g BW X day, ip) to male hyt/hyt mice for 18 days restored SMG renin-1 and EGF to near-normal levels. The weights of SMG, seminal vesicle, and epididymis were also lower in hypothyroid mice and increased in response to T4. The effect on SMG renin-1 and EGF of either DHT (150 micrograms/g BW every other day, sc) or T4 (0.025-2.5 micrograms/g BW.day, ip) was blunted in female hyt/hyt mice. A combination of DHT and T4 (0.1 microgram/g BW.day) that restored total circulating T4 and T3 to physiological levels acted synergistically to increase SMG renin-1 and EGF. The administration of 2.5 micrograms T4/g BW.day plus DHT for 7 days increased the specific activity of SMG renin-1 and EGF to levels approaching those in euthyroid littermates given the same treatment. T4 (0.1 microgram/g BW.day) did not alter the quantity or sedimentation characteristics of high affinity androgen-binding protein in SMG from female hyt/hyt mice and induced SMG renin-1 in Tfm/Y mice. Thus, T4 does not appear to exert its effect via the androgen receptor. The administration of DHT and T4 to female hyt/hyt mice produced lower circulating levels of both T3 and T4 than the same dose of T4 given alone, suggesting that DHT does not act by enhancing the conversion of T4 to T3. This study demonstrates that the interaction of T4 and DHT is not a pharmacological phenomenon, but occurs at doses of T4 that restore serum T3 and T4 in female hyt/hyt mice to normal or near-normal levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1984

Cutaneous insulin allergy responsive to oral desensitisation and aspirin.

A diabetic man with no previous history of allergy began to suffer itchy, painful swelling at the sites of injection after three months' treatment with bovine insulin. Insulin specific IgE concentrations (1.2-2.0 U/ml) were higher than in non-allergic diabetics (mean 0.4 (SD 0.06) U/ml) but lower than in most other patients allergic to insulin (1.0-19.0 U/ml). Standard approaches failed to overcome the allergic reaction, and four separate attempts at desensitisation were unsuccessful. The patient was then given oral insulin 800 U thrice daily together with enteric coated aspirin 1300 mg thrice daily for one week, and subsequent desensitisation with neutral insulin injection was carried out successfully. On stopping the aspirin the original reactions returned, and aspirin was therefore reinstituted as a permanent part of treatment. Whatever the mechanism in this patient, oral desensitisation and aspirin provided a simple method for treating a difficult condition.

Administration, Oral↗
PubMed1984

Concentration and particle size distribution in smoke from marijuana cigarettes with different delta 9-tetrahydrocannabinol content.

Particle size and mass concentration are important determinants of site and quantity of respiratory tract deposition of aerosols. Particle concentrations and size distributions of smoke from marijuana cigarettes with different concentrations (as measured in the marijuana leaf) of delta 9-tetrahydrocannabinol (delta 9-THC) were measured using a single particle aerodynamic relaxation time (SPART) analyzer. The SPART analyzer measures aerodynamic diameter of single suspended particles at a rate of 3000/min. Cigarettes were smoked using a 35-cc, 2-sec puffing device attached to a diluter; dilution and analysis were completed within 4 sec of puff generation. The size distribution of smoke from all marijuana cigarettes was similar to that for tobacco cigarettes, ranging from 0.35 to 0.43 micron (count median aerodynamic diameter). The particle number and mass concentration increased as delta 9-THC concentration increased, being, respectively, 2.2- and 3.8-fold higher in the marijuana cigarette leaf with highest delta 9-THC concentration compared to the placebo marijuana cigarette. These data indicate the need for quantitative comparisons of other potentially toxic constituents in marijuana cigarettes of different delta 9-THC concentrations.

Cannabis↗
PubMed1984

Endocrine and genetic characterization of cousins with male pseudohermaphroditism: evidence that the Lubs phenotype can result from a mutation that alters the structure of the androgen receptor.

Impaired virilization of genetic males with testes (male pseudohermaphroditism) can result either from deficiency in androgen production or defects in androgen action, the latter most commonly involving an abnormal androgen receptor. We report here two maternal cousins with male pseudohermaphroditism and clinical features characteristic of the Lubs phenotype, namely apparent females with sufficient fusion of the labioscrotal folds so that a single urogenital sinus orifice is present. Testosterone levels in these genetic males rose appropriately after administration of human chorionic gonadotropin. The amount (maximal binding capacity of 24 to 30 fmol/mg protein) and hormone binding affinity (half-maximal saturation of 0.2 nM) of the androgen receptor in cultured skin fibroblasts was normal, but the receptor was qualitatively abnormal as evidenced by instability on sucrose density gradient centrifugation. The pattern of inheritance in this family is compatible with X-linkage. These findings, together with previous studies, indicate that the spectrum of abnormalities that result from defects of the androgen receptor in genetic men can encompass the entire spectrum between male and female phenotypes.

Chorionic Gonadotropin↗
PubMed1984

A mutation that causes lability of the androgen receptor under conditions that normally promote transformation to the DNA-binding state.

Dihydrotestosterone-receptor complexes formed in human fibroblast cytosol prepared at 0 degrees C in the presence of sodium molybdate can be readily transformed to the DNA-binding state by heating at 25 degrees C. Under these conditions 50-70% of dihydrotestosterone-receptor complexes bind to DNA. We describe here studies of the transformation process in cytosols derived from normal cells and from fibroblasts propagated from subjects with syndromes of androgen resistance. In contrast to the situation with dihydrotestosterone, normal testosterone-receptor complexes are unstable under in vitro transforming conditions. Although equal amounts of hormone-receptor complex are formed at 0 degrees C, only 15% of testosterone-receptor complexes remain stable and acquire DNA-binding capacity after warming. This instability is not reversible upon lowering the temperature and is corrected by low concentrations (0.25 microM) of the protease inhibitor leupeptin. We have also identified two cousins with androgen resistance whose androgen-receptor complexes exhibit similar in vitro transformation lability with both dihydrotestosterone and testosterone. Phenotypic evidence in these subjects indicates that dihydrotestosterone-mediated processes are more completely impaired than are testosterone-mediated events. These findings suggest that dihydrotestosterone may amplify the androgenic signal at its targets not only by its higher affinity for the receptor but also by its more efficient conversion to the DNA-binding state and that such amplification may be less critical in target tissues in which testosterone suffices for androgenic effect. This offers one possible explanation of how a mutation that affects a single receptor protein may differentially impair the actions of two binding ligands of the receptor.

Child, Preschool↗
PubMed1984

High dose androgen therapy in male pseudohermaphroditism due to 5 alpha-reductase deficiency and disorders of the androgen receptor.

We describe the clinical and biochemical features of six men with male pseudohermaphroditism due to androgen resistance. Each of the subjects had male-gender behavior but incomplete virilization. The underlying defects in androgen metabolism were defined by studies of the 5 alpha-reductase enzyme and the androgen receptor in fibroblasts cultured from biopsies of genital skin. Four of the six have 5 alpha-reductase deficiency, and two have defects of the androgen receptor (the Reifenstein syndrome). The responses of these men to androgen treatment were assessed by monitoring nitrogen balance, plasma luteinizing hormone (LH) values, and clinical parameters of virilization including penile growth, potency and ejaculatory volume, muscle bulk, and growth of body and facial hair. In all of the subjects with 5 alpha-reductase deficiency and one man with the Reifenstein syndrome significant response occurred, as evidence by nitrogen retention, lowered plasma LH levels, and improved virilization, with doses of parenteral testosterone esters that raised plasma testosterone levels above the normal male range and brought plasma dihydrotestosterone levels into the normal male range. The subject who did not respond with clinical virilization nevertheless showed nitrogen retention in response to acute testosterone administration. This patient had a profound deficiency of the androgen receptor, whereas the man with a receptor defect who did respond clinically to therapy had normal amounts of a qualitatively abnormal receptor. We conclude that high dose androgen therapy may be of benefit in improving virilization, self-image, and sexual performance in subjects with 5 alpha-reductase deficiency who have male-gender behavior and in some subjects with defects of the androgen receptor.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor.

Feminization in men occurs when the effective ratio of androgen to estrogen is lowered. Since sufficient estrogen is produced in normal men to induce breast enlargement in the absence of adequate amounts of circulating androgens, it has been generally assumed that androgens exert an antiestrogenic action to prevent feminization in normal men. We examined the mechanisms of this effect of androgens in the mouse breast. Administration of estradiol via silastic implants to castrated virgin CBA/J female mice results in a doubling in dry weight and DNA content of the breast. The effect of estradiol can be inhibited by implantation of 17 beta-hydroxy-5 alpha-androstan-3-one (dihydrotestosterone), whereas dihydrotestosterone alone had no effect on breast growth. Estradiol administration also enhances the level of progesterone receptor in mouse breast. Within 4 d of castration, the progesterone receptor virtually disappears and estradiol treatment causes a twofold increase above the level in intact animals. Dihydrotestosterone does not compete for binding to the progesterone receptor, but it does inhibit estrogen-mediated increases of progesterone receptor content of breast tissue cytosol from both control mice and mice with X-linked testicular feminization (tfm)/Y. Since tfm/Y mice lack a functional androgen receptor, we conclude that this antiestrogenic action of androgen is not mediated by the androgen receptor. Dihydrotestosterone competes with estradiol for binding to the cytosolic estrogen receptor of mouse breast, whereas 17 beta-hydroxy-5 beta-androstan-3-one (5 beta-dihydrotestosterone) neither competes for binding nor inhibits estradiol-mediated induction of the progesterone receptor. Dihydrotestosterone also promotes the translocation of estrogen receptor from cytoplasm to nucleus; the ratio of cytoplasmic-to-nuclear receptor changes from 3:1 in the castrate to 1:2 in dihydrotestosterone-treated mice. Thus, the antiestrogenic effect of androgen in mouse breast may be the result of effects of dihydrotestosterone on the estrogen receptor. If so, dihydrotestosterone performs one of its major actions independent of the androgen receptor.

Animals↗
PubMed1984

Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells.

The kinetics of endothelial cells during microvascular growth were studied using a model of inflammation-induced neovascularization of the rat cornea. Inflammation was produced by central silver nitrate cauterization, cellular proliferation was assessed by tritiated-thymidine autoradiography and nuclear counts on plastic sections, and formation of new vessels was studied on whole-mount preparations after vascular perfusion with colloidal carbon. The 3H-thymidine-labeling index of endothelial cells was significantly higher than normal at 1 day following cauterization, although neither mitotic figures nor vascular sprouts were present. The labeling index reached a peak at 2 days, when cell division was evidenced by mitotic figures and doubling of the number of nuclei per section. Actual vascular sprouting also began during the 1- to 2-day interval. To determine whether vascular sprouting was dependent upon endothelial cell division, proliferation was suppressed by X-irradiation (2000 or 8000 rads) prior to cauterization. In irradiated corneas displaying no cellular proliferation, vascular sprouting at 2 days was similar to that in contralateral shielded corneas. Vascular growth continued in irradiated corneas between 2 and 4 days, but at 4 days the length of the vascular ingrowth was reduced to 66.7 and 53.4% of control after 2000 and 8000 rads, respectively. Vascular ingrowth did not progress between 4 and 7 days. This study demonstrates that initial vascular sprouting does not require proliferation of endothelial cells, although under ordinary circumstances DNA synthesis has been stimulated and is in progress at the time of sprouting. After initial sprouting without proliferation, limited vascular growth can continue for about 2 more days but subsequently ceases. Ultrastructural evaluation suggested that migration and redistribution of existing endothelial cells from the limbal vessels enable vascular sprouting and elongation without cellular proliferation.

Animals↗