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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 199 records · Page 11Linked to original sources
PubMed1990

Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin.

A male infant with perineal hypospadias and a small phallus bound in chordee is described. Biochemical investigation at age 9 months after hCG stimulation revealed a testosterone to dihydrotestosterone (DHT) ratio of 40, a markedly elevated value suggestive of deficient steroid 5 alpha-reductase activity. The diagnosis of 5 alpha-reductase deficiency was confirmed by elevated urinary 5 beta/5 alpha-steroid metabolite ratios and demonstration of defective 5 alpha-reductase activity in cultured fibroblasts from the patient's scrotum and foreskin. Application of DHT cream to the patient's abdomen raised circulating levels of DHT to the adult male range. Two courses of DHT given nightly for 3 and 4 months resulted in phallic enlargement. Surgical release of the chordee and hypospadias repair have resulted in normal male appearance of the genitalia. This case illustrates the heterogeneity of the 5 alpha-reductase deficiency phenotype.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1990

Sebright and Campine chickens express aromatase P-450 messenger RNA inappropriately in extraglandular tissues and in skin fibroblasts.

As the result of a single gene mutation, Sebright and Campine chickens have increased activity of cytochrome P-450 aromatase and increased formation of estrogen in extragonadal tissues. Affected roosters develop a feminizing state characterized by a feathering pattern typical of hens. In this paper we demonstrate that the expression of extraglandular aromatase in these chickens is due to the accumulation of aromatase mRNA similar to that expressed in the ovary of Leghorn and Campine hens. Furthermore, in fibroblasts cultured from Sebright skin, but not in normal Leghorn fibroblasts, aromatase mRNA levels are enhanced in response to 5-azacytidine and sodium butyrate, and aromatase mRNA levels in these fibroblasts correlate with enzymatic activity. We conclude that the accumulation of aromatase mRNA is a critical step in the expression of this mutation.

Animals↗
PubMed1990

Definition of the human androgen receptor gene structure permits the identification of mutations that cause androgen resistance: premature termination of the receptor protein at amino acid residue 588 causes complete androgen resistance.

We have isolated and characterized the gene encoding the human androgen receptor. The coding sequence is divided into eight coding exons and spans a minimum of 54 kilobases. The positions of the exon boundaries are highly conserved when compared to the location of the exon boundaries of the chicken progesterone and human estrogen receptor genes. Definition of the intron/exon boundaries has permitted the synthesis of specific oligonucleotides for use in the amplification of segments of the androgen receptor gene from samples of total genomic DNA. This technique allows the analysis of all segments of the androgen receptor gene except a small region of exon 1 that encodes the glycine homopolymeric segment. Using these methods we have analyzed samples of DNA prepared from a patient with complete androgen resistance and have detected a single nucleotide substitution at nucleotide 1924 in exon 3 of the androgen receptor gene that results in the conversion of a lysine codon into a premature termination codon at amino acid position 588. The introduction of a termination codon into the sequence of the normal androgen receptor cDNA at this position leads to a decrease in the amount of mRNA encoding the human androgen receptor and the synthesis of a truncated receptor protein that is unable to bind ligand and is unable to activate the long terminal repeat of the mouse mammary tumor virus in cotransfection assays.

Amino Acid Sequence↗
PubMed1990

Respiratory tract deposition of ultrafine particles in subjects with obstructive or restrictive lung disease.

To evaluate the effects of lung disease on deposition of inhaled ultrafine particles (less than 0.1 micron diameter), we measured total respiratory tract deposition of nonhygroscopic particles of 0.02 to 0.24 micron in five subjects with obstructive lung disease and three subjects with restrictive lung disease and compared it with that in ten normal subjects. Deposition was measured as concentration difference of five size fractions in inhaled and exhaled air using an electrical aerosol analyzer. The data showed that deposition of these ultrafine particles was increased in subjects with obstructive lung disease when compared with normal subjects, while it was unchanged in subjects with restrictive lung disease. The increase in deposition in the subjects with obstructive lung disease was significant for particle sizes 0.04 to 0.24 micron. Possible mechanisms for increased deposition in airway obstruction include increased transit time of particles, abnormal expiratory collapse of airways due to flow limitation, and flow perturbations resulting from decreased airway caliber.

Adult↗
PubMed1990

Protein constituents of mosquito saliva: studies on Culex molestus.

The protein constituents of saliva, salivary gland extracts, haemolymph and whole body extract from the Culex molestus mosquito were compared by polyacrylamide gel electrophoresis. When developed by the sensitive silver staining technique, saliva and salivary gland extract were found to contain 15 comparable protein bands. Salivary gland extract contained additional bands, presumed to be structural proteins, and saliva contained some unique protein bands which were not present in the gland extract, possibly originating in the salivary stylet lining. Some differences were found in the protein components of salivary gland extracts prepared from mosquitoes of different ages. Salivary proteins were found to be poorly represented in both haemolymph and whole body extracts. Immunoblotting of salivary gland extract with antibody raised against pure saliva exhibited binding to at least nine protein bands indicating the potential for using salivary gland extracts in place of mosquito saliva for further studies.

Animals↗
PubMed1989

Testicular feminization in a cat.

Testicular feminization, caused by an inherited defect of the androgen receptor, was diagnosed in a domestic cat. Individuals affected with this syndrome are genetic males that have testes but fail to undergo masculinization because the internal and external genitalia cannot respond to androgens. The affected cat had the external appearance of a sexually normal female, but during surgery for ovariohysterectomy, only 2 abdominal gonads were found. Müllerian (uterus) or wolffian (epididymides) derivatives were not present. Only testicular tissue was found in histologic sections of the gonad. A normal male chromosome constitution (38,XY) was found in karyotypes prepared from lymphocyte cultures. High affinity binding of dihydrotestosterone was undetectable in fibroblasts cultured from genital skin of the affected cat, indicating that the cytosolic androgen receptor was nonfunctional. Pedigree analysis indicates that this is an X-linked disorder in cats, as it is in other mammals. Accurate diagnosis and genetic counseling are advocated to reduce the prevalence of the disorder.

Androgen-Insensitivity Syndrome↗
PubMed1989

Ultrastructural localization of RFamide-like peptides in neuronal dense-cored vesicles in the peduncle of Hydra.

The presence of Arg-Phe-amide (RFamide)-like peptides in dense-cored vesicles in neurons of the peduncle of Hydra was demonstrated by immunogold electron microscopy. Thin sections of Lowicryl-embedded tissue labeled with antisera to RFamide and 5-nm gold-conjugated, secondary antibody and of Epon-Araldite-embedded tissue labeled with 15-nm gold particles revealed a concentration of RFamide-like immunoreactivity over the granular cores of vesicles in epidermal ganglion cells. Gold-labeled, dense-cored vesicles were present in the perikaryon, long thin neurites, and axon terminals of these neurons. The aggregation of labeled dense-cored vesicles in an axon terminal on the myoneme of an epitheliomuscular cell suggests a possible function of RFamide-like peptides in neuromuscular transmission. Gold staining of dense-cored vesicles completely disappeared when the RFamide antiserum was preabsorbed with 10 micrograms/ml RFamide. These results are the first demonstration that the dense-cored vesicles of Hydra neurons contain a neuropeptide.

Animals↗
PubMed1989

Characterization and expression of a cDNA encoding the human androgen receptor.

We report the isolation of a cDNA that encodes the complete human androgen receptor. The cDNA predicts a protein of 917 amino acids with a molecular weight of 98,918. Introduction of the cDNA into heterologous mammalian cells caused expression of high levels of a protein that binds dihydrotestosterone with the affinity, specificity, and sedimentation properties characteristic of the native human androgen receptor. Comparisons with the amino acid sequence of previously cloned steroid hormone receptors revealed a high degree of sequence conservation with the progesterone, glucocorticoid, and mineralocorticoid receptors in the putative hormone and DNA-binding domain regions.

Amino Acid Sequence↗
PubMed1989

Sexual differentiation of the gonads and of the reproductive tract.

Between 1947 and 1952 Alfred Jost deduced that sexual differentiation is an ordered process in which chromosomal sex determines gonadal sex and gonadal sex in turn directs the development of phenotypic sex. This powerful formulation has been substantiated by both genetic and endocrine evidence and has had a profound impact on clinical medicine as well as on biology. The means are now at hand for dissecting the molecular mechanisms by which genetic determinants and regulatory factors interact in this cascade to produce the male and female phenotypes.

Animals↗
PubMed1989

Particle size distribution of mainstream tobacco and marijuana smoke. Analysis using the electrical aerosol analyzer.

Accurate measurement of cigarette smoke particle size distribution is important for estimation of lung deposition. Most prior investigators have reported a mass median diameter (MMD) in the size range of 0.3 to 0.5 micron, with a small geometric standard deviation (GSD), indicating few ultrafine (less than 0.1 micron) particles. A few studies, however, have suggested the presence of ultrafine particles by reporting a smaller count median diameter (CMD). Part of this disparity may be due tot he inefficiency to previous sizing methods in measuring ultrafine size range, to evaluate size distribution of smoke from standard research cigarettes, commercial filter cigarettes, and from marijuana cigarettes with different delta 9-tetrahydrocannabinol contents. Four 35-cm3, 2-s puffs were generated at 60-s intervals, rapidly diluted, and passed through a charge neutralizer and into a 240-L chamber. Size distribution for six cigarettes of each type was measured, CMD and GSD were determined from a computer-generated log probability plot, and MMD was calculated. The size distribution parameters obtained were similar for all cigarettes tested, with an average CMD of 0.1 micron, a MMD of 0.38 micron, and a GSD of 2.0. The MMD found using the EAA is similar to that previously reported, but the CMD is distinctly smaller and the GSD larger, indicating the presence of many more ultrafine particles. These results may explain the disparity of CMD values found in existing data. Ultrafine particles are of toxicologic importance because their respiratory tract deposition is significantly higher than for particles 0.3 to 0.5 micron and because their large surface area facilitates adsorption and delivery of potentially toxic gases to the lung.

Aerosols↗
PubMed1989

The effect of a 5 alpha-reductase inhibitor on androgen physiology in the immature male rat.

To provide insight into the role of 5 alpha-dihydrotestosterone (DHT) in postnatal androgen physiology, we administered the 5 alpha-reductase inhibitor finasteride to male rats from birth through the onset of puberty. In 4-week-old control rats serum testosterone levels averaged 0.21 ng/ml, and DHT levels averaged 0.64 ng/ml. By 7 weeks of age, testosterone levels increased more than 7-fold to 1.57 ng/ml, while the circulating DHT level declined to 0.26 ng/ml. In both the 4- and 7-week-old inhibitor-treated animals, circulating DHT levels were 25-50% of control values, and circulating testosterone levels were higher than control values. In 7-week-old inhibitor-treated rats, the weights of prostate, penis, seminal vesicles, and epididymal tissues were only 30-50% those of the controls. However, DHT formation is apparently not critical for postnatal development of the preputial glands or the androgen-dependent perineal muscles, since the weights of these tissues were not affected by treatment with inhibitor. Treatment with the 5 alpha-reductase inhibitor had no apparent effect on testicular histology or daily sperm production despite the fact that testicular DHT content was lower (70%) and testosterone content was higher (250%) than those in controls. We conclude that DHT formation is important for the normal postnatal growth of the prostate, seminal vesicles, epididymis, and penis and may be important for normal feedback control of testosterone production in rats, but that its formation is not critical for the onset of spermatogenesis or the development of the preputial glands or the androgen-dependent perineal muscles.

5-alpha Reductase Inhibitors↗
PubMed1989

Androgen resistance associated with a qualitative abnormality of the androgen receptor and responsive to high dose androgen therapy.

A 46,XY infant with perineoscrotal hypospadias and microphallus was identified in a family in which seven individuals have severe hypospadias that is inherited in a pattern compatible with an X-linked defect. The infant had small testes that were palpable in the labioscrotal folds, the proximal urethra was male in character, and there was no vagina. Serum testosterone rose from 0.5 to 5.1 nmol/L in response to hCG, and there was a negligible clinical response to a short term course of testosterone enanthate. A clinical diagnosis of male pseudohermaphroditism due to androgen resistance was made. Studies in cultured genital skin fibroblasts disclosed normal 5 alpha-reductase activity, a normal amount of high affinity dihydrotestosterone binding, and normal up-regulation of androgen receptors when monolayers were incubated with dihydrotestosterone or mibolerone. Fibroblast cytosol preparations contained a normal 7-8S sedimenting peak of androgen binding. However, androgen binding in monolayers decreased 60% when the assay temperature was raised from 30 to 41 C, and the dissociation rate of ligand from the receptor was enhanced 5-fold compared to the control value, establishing the diagnosis of androgen resistance due to a qualitative abnormality of the androgen receptor. Because of parental decision to raise the patient as a male, he was given two courses of high dose testosterone cypionate when he was 2.5 and 3.5 yr old (100 mg every 2 weeks for six doses). This treatment produced significant phallic growth, making it possible to undertake surgical correction of the hypospadias. We postulate that the impairment of androgen receptor function was overcome in part by the large dose of androgen.

Chorionic Gonadotropin↗
PubMed1989

Testosterone synthesis and adenylate cyclase activity in the early human fetal testis appear to be independent of human chorionic gonadotropin control.

Androgen secretion by the fetal testis is essential for male phenotypic differentiation. In the human fetus testosterone formation is initiated soon after the differentiation of the testis (approximately 8 weeks of gestation), and the maximal testosterone content in fetal testes is achieved between 10 and 15 weeks of fetal life. The testosterone content of the fetal testis declines at the beginning of the third trimester and remains low until after birth. In an effort to understand the regulation of the onset of testosterone formation in the human fetal testis we measured adenylate cyclase activity in response to hCG stimulation in homogenates of fetal testes obtained from first and second trimester human abortuses. Basal adenylate cyclase activity was 50 pmol/mg protein.min at 10 weeks gestation, the peak activity was 137 pmol/mg protein.min at 12 weeks gestation, and activity declined thereafter to 8 pmol/mg protein.min by 16 weeks gestation. NaF-stimulated (0.6 mmol/L) and forskolin-stimulated (50 mumol/L) activities were 4- to 8-fold greater than basal adenylate cyclase activities. The maximal forskolin-stimulated activity occurred at 11 weeks (803 pmol/mg protein.min), and it fell to 35 pmol/mg protein.min by 17 weeks gestation. In contrast, hCG-stimulated (1 mumol/L) adenylate cyclase activity was only slightly greater than basal rates at all ages examined. In addition, hCG did not stimulate baseline testosterone formation in minces of testes obtained between 12 and 18 weeks of gestation. These findings suggest that the onset of testosterone formation in human fetal testes may be independent of gonadotropin control.

Adenylyl Cyclases↗
PubMed1989

Role of CD4+ T-lymphocytes in rejection by mice of fetal pig proislet xenografts.

The role of T-lymphocyte subpopulations in the rejection of fetal pig proislet (islet precursor) xenografts in mice was examined with in vivo administration of monoclonal antibodies (MoAbs) to CD4+ (GK 1.5) and CD8+ (49-11.1) T-lymphocyte subsets. The data indicate that the rejection process is T-lymphocyte dependent and mediated by CD4+ T-lymphocytes. The in vivo administration of MoAbs specific for graft-borne pig leukocytes failed to prevent xenograft rejection in fully immunocompetent transplant recipients.

Animals↗