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Biomedical subjects

J D Wilson

Publications and source records attributed to J D Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Recurrent respiratory papillomatosis with pulmonary cystic disease in a child, following maternal genital warts.

Human papillomavirus (HPV) infection of the genital tract is associated with the development of genital warts. A causal link between maternal HPV infection and development of laryngeal papillomatosis in the offspring has been proposed. We report a case of pulmonary cystic disease, a rare but serious complication of laryngeal papillomatosis in a child, following maternal genital warts.

Adolescent↗
PubMed1996

Large clonal expansions of CD8+ T cells in acute infectious mononucleosis.

Primary infection with Epstein-Barr virus often results in the clinical syndrome of acute infectious mononucleosis (glandular fever). This illness is characterized by a striking lymphocytosis, the nature of which has been controversial. We show that large monoclonal or oligoclonal populations of CD8+ T cells account for a significant proportion of the lymphocytosis and provide molecular evidence that these populations have been driven by antigen. The results suggest that the selective and massive expansion of a few dominant clones of CD8+ T cells is an important feature of the primary response to this virus.

Acute Disease↗
PubMed1996

Steroid 5 alpha-reductase 2 deficiency: virilization in early infancy may be due to partial function of mutant enzyme.

Male pseudohermaphroditism due to steroid 5 alpha-reductase deficiency is the consequence of mutations in the gene encoding the type 2 isoenzyme. Most (60%) affected subjects have homozygous mutations, and the remainder are compound heterozygotes or presumed compound heterozygotes. We report an Italian subject with phenotypic and endocrine features of 5 alpha-reductase 2 deficiency who is homozygous for a substitution mutation (H231R). Although close consanguinity is not present, genealogical data demonstrated that the parents are distantly related, and both parents and the maternal grandmother are heterozygous carriers of the mutation. The fact that this particular mutation results in the formation of an enzyme with considerable residual activity may explain in part the significant degree of virilization that took place in this subject in early infancy. This same mutation (H231R) is present in heterozygous form in two other families, an African-American family and an American family of northern European descent.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Male pseudohermaphroditism due to steroid 5alpha-reductase 2 deficiency. Diagnosis, psychological evaluation, and management.

Sixteen subjects (from 10 Brazilian families) with male pseudohermaphroditism due to steroid 5alpha-reductase 2 deficiency have been evaluated in 1 clinic. The diagnoses were made on the basis of normal plasma testosterone values, normal or low plasma dihydrotestosterone levels and high testosterone/dihydrotestosterone ratios in the basal state in postpubertal subjects or after treatment with either human chorionic gonadotropin or testosterone in prepubertal subjects. The analysis of the ratios of etiocholanolone to androsterone in urine confirmed the diagnosis in all subjects who were tested, and the molecular basis of the underlying mutations was established in 9 of the families. Fourteen of the individuals were evaluated by the same psychologist. All subjects but 1 were given a female sex assignment at birth. Three of the subjects (1 the sibling of an individual who has undergone female to male social behavior) maintain a female social sex; they have been gonadectomized and treated with exogenous estrogens. Ten of 13 subjects of postpubertal age underwent a change of social sex from female to male, had surgical correction of the hypospadias, and were treated with high-dose testosterone esters by parenteral injection and subsequently with dihydrotestosterone cream. These regimens brought serum dihydrotestosterone levels to the normal male range (or above) but resulted only in limited growth of the prostate and penis and, in some, increase in body and facial hair and enhancement of libido and sexual performance. Treatment of the prepubertal boys with testosterone and/or dihydrotestosterone resulted in a doubling of penis size.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Regulation of immunoreactive androgen receptor in the adrenal gland of the adult rat.

The androgen receptor (AR) was measured by an immunoblot assay in adult tissues of both male and female rats. Relatively high levels of AR were detected in tissues of the male urogenital tract and in the adrenal glands and gonads of both sexes. Another group of tissues, including the male levator ani/bulbocavernosus muscles, preputial gland, scrotal skin, and vagina, had low, but detectable, levels of AR. In a third group of tissues, including the uterus, kidney, spleen, liver, gut, heart, lung, pituitary, and hypothalamus, AR was undetectable. In some androgen target tissues, such as the penis, androgens cause an apparent disappearance of AR from the tissue, and in other tissues, such as the ventral prostate, androgen therapy increases the amount of detectable AR. We compared the effect of androgen on AR levels in the adrenal gland and ventral prostate, tissues that differ markedly in their trophic responses to androgen. Castration appeared to have no effect on the amount of detectable AR in the adrenal gland, whereas it caused a profound decrease in AR levels in the ventral prostate. By contrast, 7 days after hypophysectomy, AR levels declined in both the adrenal gland and the ventral prostate. The effects of hypophysectomy plus castration were similar to those of hypophysectomy alone. Administration of ACTH to hypophysectomized rats for 7 days did not reverse the effects of hypophysectomy on adrenal AR, nor did treatment with levothyroxine, dexamethasone, rat GH, or rat PRL. Treatment of hypophysectomized rats with 5alpha-dihydrotestosterone for 7 days caused a dramatic increase in the amount of detectable AR in both the ventral prostate and the adrenal gland, but had a trophic effect only in the ventral prostate. These findings suggest that the amount of immunoreactive AR detected in both the adrenal gland and the ventral prostate is enhanced by androgens: testicular androgens in the case of the ventral prostate and adrenal androgen in the case of the adrenal glands.

Adrenal Glands↗
PubMed1996

Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency.

Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Role of dihydrotestosterone in androgen action.

Androgen action differs from that of most hormones in the testosterone, the major androgen secreted from the testes and the most abundant androgen in the circulation of men, is not the principal androgen within target cells. Indeed, abundant evidence indicates that most androgen actions are mediated by the 5alpha-reduced metabolite dihydrotestosterone that is formed in target tissues. The conversion of testosterone to dihydrotestosterone is mediated by two isoenzymes; mutations in the steroid 5alpha-reductase 2 gene cause a rare autosomal-recessive form of male pseudohermaphroditism, and inhibition of this enzyme causes regression of the prostate gland. Dihydrotestosterone binds more tightly to the androgen receptor that does testosterone, but it is not clear whether this property is the sole explanation for its essential role in androgen action. Nor is it clear whether some androgenic effects may be mediated by circulating dihydrotestosterone acting as a hormone.

Androgens↗
PubMed1995

Intragraft expression of cytokine transcripts during pig proislet xenograft rejection and tolerance in mice.

The rejection of pig proislet (islet precursor) xenografts in CBA/H mice is a CD4+ T cell-dependent process. The molecular mechanisms of xenograft rejection, xenograft survival during anti-CD4 mAb therapy and xenograft tolerance post-withdrawal of anti-CD4 mAb administration, were examined by using a semiquantitative PCR method. Temporal analysis of intragraft cytokine mRNA demonstrated a Th0-like pattern of expression (IL-2, IFN-gamma, IL-3, IL-4, IL-5, and IL-10) on day 4 of the acute xenograft rejection process. From day 5, however, only Th2-associated transcripts (IL-3, IL-4, IL-5, and IL-10) were enhanced in xenografts compared with isograft controls. Immunohistochemistry showed that the principal participants in the rejection infiltrate were CD4+ T cells and eosinophils, with smaller numbers of CD8+ T cells. In vivo depletion of CD4+ T cells prevented xenograft rejection but had minimal effect on the peak levels of IL-2, IFN-gamma, and IL-10 mRNA; in contrast, the enhanced expression of IL-3, IL-4, and IL-5 transcripts seen in rejecting xenografts was abrogated. This established a positive correlation between acute xenograft rejection, presence of CD4+ T cells, and enhanced intragraft expression of mRNA for the Th2-type cytokines IL-3, IL-4, and IL-5. In tolerant hosts, long-term proislet xenograft survival and function (> 190 days) was accompanied by intragraft expression of IL-2 and IL-10 mRNA; IFN-gamma, IL-3, IL-4, and IL-5 mRNA were either undetected or not enhanced. The induced rejection of long-term functioning xenografts (> 170 days) in nontolerant hosts resulted in selective enhancement of IL-4 transcript expression. This study suggests that Th2-like CD4+ T cells are differentially activated in response to xenoantigen and that xenograft tolerance is associated with lack of expression of the Th2 cytokine, IL-4.

Animals↗
PubMed1995

Time-quantified fetal movement detection with two-transducer data fusion.

OBJECTIVE: Our purpose was to develop an automated ultrasound-based fetal movement detection system to better define fetal movements. STUDY DESIGN: One hundred one patients had fetal movements recorded over a 20-minute period. Results of movement detection by a single-transducer system (Russell 1) and a two-transducer fusion system (Russell 2) were compared with those of Hewlett-Packard (HP-M-1350-A), maternal perception, and expert ultrasonography review. RESULTS: A total of 86,592 seconds of videotape was scored for fetal movement. Russell 2 had a second-per-second sensitivity of 57.21% compared with Russell 1 at 40.95%, the HP-M-1350-A at 31.44%, and maternal perception at 30.80%. Russell 2 detected 67.57% of discrete movements compared with 57.52%, 41.98%, and 37.92%, respectively, in other systems. CONCLUSION: Russell 2 represents a significant improvement over existing systems in detection of fetal movements on a second-per-second basis.

Adolescent↗
PubMed1995

A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia.

Leydig cell hypoplasia (LCH) is a form of male pseudohermaphroditism in which Leydig cell differentiation and testosterone production are impaired. This report describes the first case of a nonsense mutation (A1635C) in exon 11 of the human luteinizing hormone receptor (hLHR) gene in two sisters with LCH. This mutation causes loss of function of the receptor by introducing a stop codon at residue 545 in transmembrane helix 5 of the hLHR. Surface expression of the truncated hLHR (hLHR-t545) in human embryonic kidney cells stably transfected with cDNA encoding hLHR-t545 was diminished compared to the wild-type hLHR and hCG-induced cAMP accumulation was impaired. These results establish that single base mutations in exon 11 of the hLHR gene can produce inactivation as well as activation of the hLHR. Furthermore, they demonstrate that functional domains between transmembrane helix 5 and the C-terminal cytoplasmic tail of the hLHR are required for normal cell surface expression of the receptor and signal transduction.

Base Sequence↗