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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 379 records · Page 21Linked to original sources
PubMed1977

Estrogen formation by the ovary of the rabbit embryo.

The conversion of [1,2,6,7-3H]- testosterone to radioactive estradiol was assessed in tissue slices of 18 different tissues from rabbit embryos that varied in age from 16 to 29 days gestation. Significant rates of estradiol synthesis were demonstrated only in ovaries [4.2 +/- 0.7 (mean +/- SEM) pmol/h/mg) protein], placenta (0.7 +/- 0.2 pmol/h/mg protein) and brain (0.3 +/- 0.1 pmol/h/mg protein). Estradiol formation was undetectable in day 16 gonads of both sexes and in tests at all ages examined, but by day 18 it was demonstrable in ovaries and rose rapidly to reach a level of 6 pmol/h/mg protein by day 19. The time of appearance of the enzymatic capacity to convert testosterone to estradiol in the ovary is similar to the onset of the enzymatic capacity to form testosterone by the fetal testis, suggesting that the acquisition of the enzymatic activies that allow specific endocrine function by these two tissues may be regulated by the same or similar factors during embryonic development.

Androstenedione↗
PubMed1977

Formation of 5alpha-androstane-3alpha,17beta-diol by normal and hypertrophic human prostate.

The 3-keto reduction of [1,2-3H]dihydrotestosterone to 3alpha- and 3beta-androstanediols was assessed in homogenates of 40 prostates obtained either at surgery or at medicolegal autopsy from men who had died suddenly. Formation of both androstanediols was demonstrable in cytosol and in microsomes, and both NADH and NADPH were effective cofactors for the two reactions. Formation of the two steroids was not influenced by storage of the gland for up to 8 h prior to processing. When NADPH was cofactor, the formation of 3alpha- and 3beta-androstanediol was significantly higher in microsomes and cytosol from hypertrophic than from normal glands.

Adult↗
PubMed1977

Studies on the pathogenesis of the incomplete forms of androgen resistance in man.

The affinity and turnover of the specific dihydrotestosterone binding protein have been assessed in fibroblasts cultured from genital skin from a variety of control subjects and from 4 patients with incomplete hereditary male pseudohermaphroditism due to androgen resistance (incomplete testicular feminization and Reifenstein syndrome). Whereas the amount of dihydrotestosterone binding in the 4 mutant cell strains is low, both the affinity of the protein for dihydrotestosterone as assessed by the concentration at which half-maximal binding occurs (averaging 0.2 nM) and the turnover of the binding protein (average half-life of 11--13 h) are within the normal range. Since no qualitative abnormality could be detected, these data suggest that the mutations in these two disorders affect the synthesis of the dihydrotestosterone binding protein.

Androgen-Insensitivity Syndrome↗
PubMed1977

Increased EA-rosette formation by lymphocytes from patients with rheumatoid arthritis.

A modified method for estimating erythrocyte-antibody (EA) rosette formation of human peripheral blood lymphocytes (PBL) reveals consistent differences between rheumatoid arthritis (RA) patients tested and healthy control subjects. Using this method we find an average of 27 +/- 0-8% (standard error of mean) of PBL from 120 RA patients forming EA rosettes in contrast to only 6 +/- 0-6% of PBL from ninety-five healthy controls, and 7 +/- 0-9% from eighteen patients with systemic lupus erythematosus (SLE). This difference is not due to monocytes forming EA rosettes or to T-cell sheep red blood cell (SRBC) binding. The concentration of antibody used in our assay appears to highlight the RA-control differences--suggesting a possible qualitative difference in EA-binding capacity. We find no correlation between EA binding and disease duration or rheumatoid factor titre. The assay is susceptible to technical variation, and the effects of antibody concentration, lymphocyte to SRBC ratio, method of blood collection and lymphocyte-separation procedure have all been evaluated.

Antibodies↗
PubMed1976

T-lymphocyte colonies in malignant disease.

T-lymphocyte colonies have been cultured in 106 subjects comprising healthy individuals and hospital inpatients as controls and patients with a wide variety of malignancies. Abnormal results were recorded in 89% of patients with malignant disease and in 23 of 24 patients with carcinomas (96%). This test may be valuable in research, and in diagnosis and monitoring of progress in malignant disease.

Adolescent↗
PubMed1976

Practolol and the safety of other beta blockers.

Recognition of the "occulomucocutaneous syndrome" related to practolol administration has caused the safety of other beta-blocking agents to come under close scrutiny. No satisfactory means of screening for at-risk patients is available. ANF estimation, has considerable limitations as both a screening and a diagnostic procedure. Patients with skin lesions alone may not be positive, while even advanced cases often show very low titres. There are important technical difficulties with the assay and interpretation of results is hindered by an increase in incidence of the antibody with age, in females, and in patients on a wide variety of other therapeutic agents.

Adrenergic beta-Antagonists↗
PubMed1976

Steroid 5alpha-reductase in cultured human fibroblasts. Biochemical and genetic evidence for two distinct enzyme activities.

Various properties of the steroid 5alpha-reductase have been examined in cell-free extracts of skin and of fibroblasts cultured from genital and nongenital skin from control subjects and from patients with several forms of male pseudohermaphroditism. When 20alpha-hydroxy-4-[1,2-3H] pregnen-3-one was used as substrate, two 5alpha-reductase activities could be demonstrated in intact skin and cultured fibroblasts. The major activity, previously described for microsomes from human prepuce and extracts of cultured foreskin fibroblasts, is characterized by a narrow pH optimum near 5.5 and is limited to fibroblasts derived from genital skin. A second activity, not limited by the site of biopsy, has been demonstrated over a higher and broader range of pH (from 7 to 9); this enzyme activity is found in both genital and nongenital skin and in fibroblasts cultured from all skin regions. Whereas there is wide variability in the activity at pH 5.5 in genital skin fibroblasts, the activity at pH 7 to 9 is similar in fibroblasts derived from all anatomical sites. The two activities exhibit different kinetics with respect to steroid substrate and are also dissimilar in their subcellular distributions. Other properties, such as coenzyme requirement, steroid substrate specificity, and instability with increasing temperature, appear to be similar.

Cells, Cultured↗
PubMed1976

Human T lymphocyte colonies in agar: a comparison with other T cell assays in healthy subjects and cancer patients.

Colonies of human lymphocytes with T cell characteristics will grow in agar from repeated mitotic divisions with phytohaemagglutinin (PHA) stimulation. The colonies comprise spheres of tightly-packed cells with up to 500-1,000 blast-like cells in each colony. 65% of cells from pooled colonies bound AET-treated sheep red cells. 1,100-2,500 colonies/10(6) peripheral blood lymphocytes developed when cell donors were healthy but lower numbers (350-1,000 colonies/10(6) lymphocytes) were detected in blood from cancer patients. Comparison with other non-specific assays of cell-mediated immunity showed that while 66% of cancer patients were anergic (to five recall antigens) and 78% exhibited depressed mitotic activity in standard cultures with low dose PHA, 100% of these patients revealed T cell colony formation below normal. It is suggested that further studies of T lymphocyte colony-forming cells in healthy people and in a number of disease states may significantly advance our understanding of mechanisms of cell-mediated immunity.

Agar↗
PubMed1976

Nature of the union between sheep red blood cells and T lymphocytes.

Calcium ions acting as salt bridges between the receptor on T lymphocytes and the negatively charged sites on sheep red blood cells (SRBC) are probably involved in rosette formation. Evidence to support this hypothesis includes the results of manipulating the ionic concentration of Ca2+free incubation medium and rosette inhibition in the presence of EDTA. Optimal rosette formation occurred when NaCl was the supporting electrolyte and the ionic strength was 100-150 mM. Neither KCl, CaCl2, MgCl2 nor Na2SO4 were effective as supporting electrolytes. SRBC pretreated with neuraminidase showed improved rosette formation of lower ionic strength than control cells.

Animals↗
PubMed1976

The induction of prostatic hypertrophy in the dog with androstanediol.

The effects of androstanediol and estradiol on prostatic growth were investigated in castrate dogs. Estrogens along resulted in no significant change in prostatic weight, whereas androstanediol produced growth comparable to that in uncastrated controls. Androstanediol plus estradiol resulted in an even more striking increase in prostate growth. Approximately half the animals receiving androstanediol alone and all of those receiving androstanediol plus estradiol fulfill the weight and histological criteria for prostatic hypertrophy in the dog. Since both these steroid hormones are presumed to be normal secretory products of the testis, it is possible that they are involved in the pathogenesis of prostatic hypertrophy in the dog.

Androstane-3,17-diol↗
PubMed1976

Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.

Dihydrotestosterone binding was measured in culture fibroblasts from 14 control subjects and from 12 patients with five different types of hereditary male pseudohermaphroditism. Two assays of binding were used--an intact monolayer assay and density gradient centrifugation of cell extracts. In the intact monolayer assay of normal cells the uptake of [3H]dihydrotestosterone consisted of two components. The first was a high affinity component that exhibited saturation at approximately 1 nM dihydrotestosterone. The second was a low affinity component that was not saturable with concentrations of steroid up to 5 nM. Twice the number of high affinity binding sites were present in fibroblasts grown from genital skin (foreskin, labia majora, and scrotum) as from nongenital sites (37 vs. 14 fmol/mg protein). In the density gradient assay in 5-10% sucrose, the major peak of dihydrotestosterone binding was in the 8S region in low molarity buffer and in the 4S region in 0.5 M KCl. High affinity binding was normal in cells from two patients with familial incomplete male pseudohermaphroditism, type 2, an autosomal recessive defect in which dihydrotestosterone formation is deficient, and in cells from a patient with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency, an autosomal recessive defect of testosterone synthesis. High affinity binding was low by both methods in fibroblasts from five patients with complete testicular feminization. Furthermore, binding by both methods was also low in cells from three subjects with familial incomplete male pseudohermaphroditism, type 1, a presumed X-linked recessive disorder of androgen resistance, and in fibroblasts grown from a subject with the incomplete form of testicular feminization. The finding that dihydrotestosterone binding is abnormal in two forms of hereditary androgen resistance in addition to complete testicular feminization suggests either that these disorders are the result of allelic mutations affecting the function of the androgen-binding protein or that normal dihydrotestosterone binding requires the participation of more than one gene product.

Binding Sites↗
PubMed1976

Cytosol androgen binding in submandibular gland and kidney of the normal mouse and the mouse with testicular feminization.

Androgen binding was investigated in the cytosol of the submandibular gland and the kidney from normal mice, mice with testicular feminization (Tfm), and carriers of the Tfm gene. In both tissues from normal mice an androgen-binding complex was observed from birth throughout life that could not be detected in Tfm animals at any age. This complex was precipitated at 35 and 40% saturation with ammonium sulfate in the kidney and the submandibular gland, respectively, and had an approximate sedimentation coefficient of 8S in the submandibular gland and 10S in the kidney. In both tissues of the normal female, the apparent dissociation constants (Kd) for testosterone and dihydrotestosterone were about 1 nM, and the binding capacity averaged 20 fmol-mg protein-1. The number of binding sites in preparations from Tfm carriers was intermediate between that in the Tfm and the normal female . In 0.5M KCl the 8S receptor of normal submandibular gland sediments at about 3S, and the 10S receptor of normal kidney sediments at about 4.5S. In the submandibular gland, binding of approximate 3S size was also observed. The latter was present in Tfm animals as well as in normal mice, it precipitated at 70% saturation with ammonium sulfate, and it was detectable from birth. In the kidney the only low molecular weight binding for androgen was about 4.5S in size.

Androgen-Insensitivity Syndrome↗
PubMed1976

The formation of 5alpha-androstane-3alpha, 17beta-diol by dog prostate.

The 3-keto reduction of (1.2-3H)dihydrotestosterone to 3alpha and 3beta-androstanediol has been assessed in homogenates of 31 dog prostates that varied in size from less than 1 to greater than 15 g. The formation of both androstanediols was demonstrable in microsomes and cytosol, and both NADH and NADPH were effective cofactors for the two reactions. The formation of 3beta-androstanediol per unit weight of prostate or per mg protein did not show a clear-cut relation with the size fo the gland, but 3alpha-androstanediol formation per mg microsomal protein increased as a linear function with size so that the rates were on an average 10-fold greater in prostates greater than 15 g than in those less than 5 g in weight.

Androstane-3,17-diol↗
PubMed1976

Aromatization of androstenedione by cultured human fibroblasts.

The conversion of (1, 2, 6, 7-3H)androstenedione to (3H)estrone was measured in fibroblast monolayers grown from biopsies of genital and nongenital skins obtained from 15 control subjects, 9 males with developmental defects of the urogenital tract, and 8 patients with hereditary male pseudohermaphroditism. Under the standardized conditions utilized in this study, the rate of estrone formation in the fibroblasts from normal controls varied from less than 0.2 to 5.5 pmol/100 mg protein/h, and these rates were enhanced by incubation of intact monolayers with choleragen, theophylline, or dexamethasone. Rates of estrone formation were higher in some foreskin strains grown from subjects with developmental defects of the urogenital tract and in strains from scrotum and foreskin of patients with familial incomplete male pseudohermaphroditism, types 1 and 2 than in normal strains or strains from patients with testicular feminization. The meaning of these apparent high rates of estrone formation is unclear.

Adolescent↗
PubMed1976

Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome.

We describe 14 patients with congenital absence of the vagina associated with a variable abnormality of the uterus and review the literature. Associated developmental anomalies of the urinary tract and skeleton are common. As a result of the analysis of two affected families, we believe that the disorder may represent the variable manifestation of a single underlying genetic defect that can be expressed alone or in any combination of vertebral, renal, and genital abnormalities. Some affected persons may have lethal manifestations such as absence of both kidneys, and some cases may result from multifactoral causes rather than a single gene defect. Whatever the cause, the defect involves mesodermal development and the mesonephric kidney, the latter resulting in abnormalities in the paramesonephros (uterus and vagina) and in the metanephric kidney. Both nonoperative and surgical treatments are generally successful in repairing the vaginal abnormality.

Adolescent↗