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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 217 records · Page 12Linked to original sources
PubMed1988

The expression of a functional cDNA encoding the chicken cytochrome P-450arom (aromatase) that catalyzes the formation of estrogen from androgen.

A complementary DNA (cDNA) copy of the aromatase P-450 has been isolated from a chicken ovary library using as probe a partial cDNA believed to encode the human placental aromatase. The predicted amino acid sequence of the chicken aromatase cDNA possesses regions of homology to that of its human counterpart, but only limited homology to other cytochrome P-450 enzymes. The introduction of the cDNA clone into COS-1 cells results in the production of high levels of aromatase activity. The chicken enzyme is targeted to the appropriate subcellular fraction in the transfected COS cells, and the apparent Km of the chicken aromatase activity, measured in microsomes prepared from the transfected cells, is similar to that of the enzyme prepared from chicken ovary microsomes. These findings establish that the cDNA clone encodes chicken ovarian aromatase and demonstrate that this protein can catalyze the three successive oxidation reactions necessary to form estrogen from androgen.

Amino Acid Sequence↗
PubMed1988

Specificity of androgen resistance in Mus caroli kidney.

Androgen controls the expression of beta-glucuronidase and several other proteins in the kidney of the standard laboratory mouse, Mus musculus. Other species within the genus Mus exhibit a variety of response patterns for kidney beta-glucuronidase and other markers of androgen action. We have investigated the mechanism of androgen action in M. caroli, a Mus species that does not produce beta-glucuronidase in response to testosterone. The failure of testosterone to induce beta-glucuronidase in M. caroli females cannot be overcome by treatment with dihydrotestosterone, with pharmacological doses of testosterone propionate or dihydrotestosterone propionate, or with a variety of potent androgen analogues. All of these compounds induce kidney beta-glucuronidase in M. musculus females and kidney ornithine decarboxylase, submandibular gland renin, and submandibular gland epidermal growth factor in both M. caroli and M. musculus females. Furthermore, kidney androgen receptor proteins from M. caroli and M. musculus animals have the same sedimentation characteristics on sucrose density gradients. These data indicate that androgen resistance in M. caroli is not due to deficient 5 alpha-reductase or aberrant hormone metabolism producing suboptimal levels of functional androgen and is not caused by a defective androgen receptor. They suggest that the resistance of beta-glucuronidase in M. caroli kidney to induction by androgen occurs at the level of the beta-glucuronidase gene.

Androgens↗
PubMed1988

Value of colposcopy in genitourinary departments.

During 18 months 237 colposcopies were performed on 227 patients in the department of genitourinary medicine, Sheffield. Histological evidence of cervical intraepithelial neoplasia was found in 118 patients (52%), of whom 104 (88%) were aged under 35, 93 (79%) under 30, and 64 (54%) under 25. Most were treated with local destructive treatment, only five (4%) requiring cone biopsy. Colposcopy in a genitourinary department has an important part to play in detecting cervical intraepithelial neoplasia, particularly in younger women. Early diagnosis may often facilitate using local destructive treatment, thereby reducing the numbers of patients needing cone biopsy.

Adolescent↗
PubMed1988

A mutation of the androgen receptor associated with partial androgen resistance, familial gynecomastia, and fertility.

A family is described in which gynecomastia and undervirilization in five men (four of whom have fathered children) were inherited in a manner compatible with an X-linked defect. Three members from whom blood could be obtained had supranormal serum testosterone and normal LH and FSH levels. One man had severe oligospermia with decreased motility, and one had normal sperm density and motility. In fibroblasts cultured from genital skin biopsies from two of the men, the levels of androgen receptor and affinity of binding of receptor to dihydrotestosterone were normal. However, androgen binding in fibroblast monolayers was thermolabile, up-regulation of receptor levels did not occur after prolonged incubation of monolayers with dihydrotestosterone or methyltrienolone, and dissociation rates at 37 C were increased with the synthetic androgen mibolerone. In addition, in cytosol preparations the androgen receptor protein was unstable. This disorder probably represents the most subtle functional abnormality of androgen receptor characterized to date, since it is compatible with normal male phenotypic development and in some affected men with fertility. It follows that infertility is not an invariable feature of androgen resistance as we previously suggested.

Adolescent↗
PubMed1988

The androgen receptor in the fetal epididymis is similar to that in the mature rabbit.

To provide insight into the mechanism of wolffian duct virilization the androgen receptor has been characterized in pooled epididymal tissue from Day 27 rabbit embryos. Although the receptor is present at levels about a tenth that of other androgen target tissues in rabbit embryos, it appears to be a typical androgen receptor in regard to sedimentation characteristics and preferential binding of 5 alpha-dihydrotestosterone over testosterone. Thus, the mechanism by which testosterone virilizes the wolffian duct cannot be explained by unique binding characteristics of the androgen receptor in tissues derived from the wolffian ducts.

Animals↗
PubMed1987

The evaluation of biological interactions using response surface methodology.

Response surface methodology was employed in the statistical analysis of the combination exposures of genotoxic agents, bischloroethylnitrosourea with cis-diamminedichloroplatinum (II) and cis-diamminedichloroplatinum (II) with X rays. The measured endpoint in each case was sister chromatid exchanges in V79 Chinese hamster cells. The combination experiments employed a factorial design in which cells were treated, in various concentration combinations, with two agents simultaneously. Bis-chloroethylnitrosourea and cis-diamminedichloroplatinum (II) each exhibited curvilinear concentration-related increases in sister chromatid exchanges. X rays exhibited a dose-dependent increase in sister chromatid exchanges. For the cis-diamminedichloroplatinum (II)/X ray combinations, response surface methodology indicates a less-than-additive interaction, suggested by the non-parallel concentration-response curves of one agent at varying concentrations of the other, and a slight dose-dependent increase in sister chromatid exchanges due to X rays alone. Both cis-diamminedichloroplatinum and bis-chloroethylnitrosourea exhibited concentration-related increases in sister chromatid exchanges, cis-diamminedichloroplatinum (II) being 8-10 times (dependent on what level of effect was compared) more potent than bis-chloroethylnitrosourea. For the cis-diamminedichloroplatinum (II)/bis-chloroethylnitrosourea combinations, an increasingly less-than-additive interaction was detected. The analysis of these combinations demonstrates the strength of response surface methodology, a collection of mathematical and statistical techniques for detecting, analyzing and describing the biological effects resulting from exposures to multiple cytotoxic agents. The descriptive ability of these procedures is shown to be useful in that it leads to the suggestion of hypotheses regarding mechanisms of action.

Animals↗
PubMed1987

Linkage analysis with RFLPs in families with androgen resistance syndromes: evidence for close linkage between the androgen receptor locus and the DXS1 segment.

Three families with androgen resistance syndromes--two with testicular feminization and one with Reifenstein syndrome--have been studied for linkage analysis. Using three cloned DNA sequences from the centromere region and the proximal long arm of the X chromosome (p8, pDP34, and S9, which define respectively the chromosomal segments DXS1, DXYS1, and DXS17), we found no recombination between the DXS1 locus and the mutant genes in the three families. Assuming that these disorders are the result of allelic mutations at the same locus for the androgen receptor, we can conclude that there is a close linkage between DXS1 and the androgen receptor locus, with a maximum lod score zeta = 3.5 at a recombination fraction theta = 0.0 using the LIPED program (Ott 1974).

Androgen-Insensitivity Syndrome↗
PubMed1987

Surgical management of subclavian artery injury.

During a 10 year period, we have had operative experience with 13 injuries to the subclavian artery. The factors that led to the successful management in 10 consecutive patients were analyzed. Nonspecific signs, such as pain and swelling, were present in all of the patients. Some aspect of vascular injury was present in each patient and included change in the quality of the distal pulse, hematoma, active hemorrhage, and bruit. Roentgenologic signs such as lung opacification, fractured clavicle, fracture of the first or second rib, and pulmonary opacification were present in each patient. Arteriograms were obtained from all stable patients in whom this injury was suspected. There were no false-positive or false-negative findings. The operative approach for the right subclavian vessels was midline sternotomy, whereas for exposure of proximal left subclavian injuries, anterolateral thoracotomy was utilized. Claviculectomy permitted excellent exposure for distal subclavian artery injuries. This exposure was associated with minimal blood loss and permitted direct repair of complex injuries of the arteries and veins. All patients who reached the emergency room with measurable vital signs survived, and all those who underwent subclavian vascular repair had circulation restored. Principal morbidity was due to associated brachial plexus and lung injuries. A high index of suspicion, rapid transportation, aggressive resuscitation, and proper surgical exposure and repair are essential for the successful management of these rare vascular injuries.

Adult↗
PubMed1987

Evaluation of the interaction of three genotoxic agents in eliciting sister-chromatid exchanges using response surface methodology.

Chinese hamster cells (V79) were treated with ethylnitrosourea (ENU), bischloroethylnitrosourea (BCNU), and cis-diamminedichloroplatinum(II) (DDP) alone and in combination. Sister chromatid exchanges (SCEs) were quantitated as measures of genotoxicity of the three agents. The combination experiment employed a factorial design in which cells were treated, in various concentration combinations, with all agents simultaneously. Response surface methodology using a polynomial model in treatment variables to approximate the mean the distribution of SCE events was employed for analysis of the interactions of the three genotoxic agents. Due to unequal variances of the number of SCEs in the various treatment groups, a weighted least-squares analysis was used to estimate the parameters of the dose-response relationship. The single-agent results suggest that the DDP concentration-response curve has a much steeper slope than the ENU and BCNU curves, and is concave downward as compared to the relatively linear concentration-response curves of ENU and BCNU. The combination results suggest that ENU and DDP are involved in a negative interaction. The BCNU/DDP interaction, the ENU/BCNU interaction, and the three-factor interaction are not statistically significant. The analysis of these data demonstrates the usefulness of a statistical procedure for evaluating the biological effects resulting from exposure to multiple cytotoxic agents. The methodology can be used with many other types of endpoints and is not limited by the number of treatment agents.

Animals↗
PubMed1987

A dose-response curve for yusho syndrome.

Analysis of rice oil consumption by a subgroup of yusho patients and recent measurements on the composition of the oil they consumed suggest that the median dose (ED50) of polychlorodibenzofurans (PCDFs) causing "severe" symptoms was about 68 micrograms/kg body mass (range: 45-104 micrograms/kg.) (The oil consumption was estimated ex post facto in a 1968 survey of the group's eating and cooking habits.) While most authorities now agree that the PCDFs present in the contaminated rice oil caused the yusho syndrome, this ED50 estimate is rendered somewhat uncertain by the fact that cocontaminant polychloroquaterphenyls (PCQs) and -biphenyls (PCBs), both present at about 100 times greater concentration, may either augment or diminish the PCDF toxicity by an unknown amount. Nevertheless, the ED50 value quoted is consistent with what is known about the dose-response for induction of chloracne by 2,3,7,8-tetrachlorodibenzodioxin (TCDD). This finding implies that single doses of about 1/2 microgram PCDF/kg body wt will cause no adverse effects in humans. Using Poiger's estimate of the clearance rate for TCDD in humans (t 1/2 = approximately 2100 days) as a measure of the time to equilibrium for chronic ingestion, we conclude that a daily intake of 1.50 X 10(-4) micrograms PCDF/kg body mass (150 pg/kg/day) would cause no adverse effects and would represent a health-conservative basis for environmental standards. This value exceeds by 50 to 100 times the estimated present intake by North Americans of PCDFs from environmental sources (ca. 1-3 pg/kg/day).

Dioxins↗