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Biomedical subjects

B A Khalid

Publications and source records attributed to B A Khalid.

At least 109 records · Page 6Linked to original sources
PubMed1983

Adrenalectomy and glucocorticoid administration in vivo do not affect production of 6-oxoprostaglandin F1 alpha by rat aortae.

1. Rats were bilaterally adrenalectomized and treated for periods of up to 32 days with doses of dexamethasone equivalent to physiological and supraphysiological endogenous glucocorticoid secretion. Aortic production of 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) was measured by radioimmunoassay of the supernatant fluid from rings of aorta incubated in vitro. 2. Up to 32 days after adrenalectomy, neither adrenalectomy nor dexamethasone (2 micrograms/day and 20 micrograms/day) influenced aortic 6-oxo-PGF1 alpha production. 3. High doses of dexamethasone (60 micrograms/day for 6 days) in the presence or absence of mineralocorticoid (11-deoxycorticosterone, 600 micrograms/day) had no effect on aortic 6-oxo-PGF1 alpha production. 4. In contrast to the lack of effect of dexamethasone administered in vivo, incubation of aortic discs for 5 h with dexamethasone (1 mumol/l) in vitro caused inhibition of aortic 6-oxo-PGF1 alpha production to 23% of control levels. 5. Alteration in endogenous glucocorticoid secretion is unlikely to be involved in the physiological regulation of aortic 6-oxo-PGF1 alpha production.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Cystic fibrosis and normal fibroblasts have identical glucocorticoid receptor profiles and induced protein responses.

The possibility of differences in glucocorticoid sensitivity between normal and cystic fibrosis fibroblasts was studied in cultured cells derived from forearm skin biopsies. Both normal and cystic fibrosis cells bound tritiated dexamethasone with high affinity (Kd 37 degrees C approximately equal to 10 nmol/1) to a limited class of sites (concentration approximately equal to 50,000/cell); no difference between cystic fibrosis and normal cells was seen in the nuclear transfer of receptor-bound tritiated dexamethasone. After 4 h exposure to dexamethasone and analysis of 35S-methionine labelled proteins by 2-dimensional gel electrophoresis, both normal and cystic fibrosis cells showed increased abundance of protein kappa (molecular weight approximately equal to 41,000; pKi approximately equal to 6.5) over non-steroid exposed gels. After 16 h exposure, in both cystic fibrosis and normal cells exposed to dexamethasone a decrease in protein omega (mol. wt approximately equal to 42,000; pKi approximately equal to 5.4) was seen compared with control. We interpret these data as evidence against a difference in glucocorticoid receptor of effector mechanisms between cystic fibrosis and normal fibroblasts.

Adolescent↗
PubMed1983

Correlations between fibroblast androgen receptor levels and clinical features in abnormal male sexual differentiation and infertility.

Androgen receptor binding of radiolabelled methyltrienolone (3H-R1881) was determined in cultured genital skin fibroblasts from 17 normal male controls and from 65 males with genital abnormalities. Analysis of the results was performed with patients grouped according to the predominant clinical features. Of 16 patients with complete male pseudohermaphroditism, 12 had androgen receptor (AR) deficiency, one had "receptor-positive" Testicular Feminization, and in three, alternative diagnoses were established (17 alpha hydroxylase deficiency; 20,22-desmolase deficiency; mixed gonadal dysgenesis). In contrast, only four of 16 patients investigated for ambiguous genitalia (phallus intermediate between male and female, perineal urethra) showed AR deficiency. Borderline or slightly low AR levels were found in each of four boys in whom the sole abnormality was micropenis. In 26 boys with penile hypospadias, however, only one had low AR. Very low levels of AR (levels comparable to those seen in complete Testicular Feminization) were found in two of three men with infertility associated with abnormally high serum testosterone levels.

Adult↗
PubMed1983

Neonatal rat hypothalamus cell culture: neuron subpopulations secrete immunoreactive beta-endorphin but not immunoreactive ACTH.

Primary cultures of dissociated hypothalamic cells were prepared from 1-day-old rat neonates. Studies with cell-specific antisera revealed the presence of neurons, glial cells, oligodendrocytes and fibroblast-like cells. By immunohistochemistry, two morphologically distinct cells in culture were positive for immunoreactive beta-endorphin (IR-beta-EP). The medium derived from these cultures contained radioimmunoassayable IR-beta-EP, but not IR-ACTH. These data suggest that, in rat neonatal hypothalamic cultures, two subpopulations of cells exist which store and secrete IR-beta-EP, but not IR-ACTH.

Adrenocorticotropic Hormone↗
PubMed1983

Defective nuclear accumulation of androgen receptors in disorders of sexual differentiation.

Nuclear transfer of androgen receptors (AR) and glucocorticoid receptors (GR) was determined in cultured genital skin fibroblasts from 10 normal controls and eight patients with abnormalities of the external genitalia. In whole cell studies, cultures were incubated for 20 min at 37 degrees C with [3H]methyltrienolone (3H-R1881) or tritiated dexamethasone, and specific binding was determined in whole cell, cytoplasmic, and crude nuclear fractions. Between normal and affected fibroblasts no difference was seen in cellular levels of GR, or in cytoplasmic and nuclear distribution of GR. In normal fibroblasts, cytoplasmic binding of 3H-R1881 represented 56%, and crude nuclear binding 44%, of total binding; in fibroblasts from five of the eight patients similar values (cytoplasmic 55% and nuclear 44%) were seen for 3H-R1881 binding. In fibroblasts from the other three patients no decrease in total cellular levels of AR were seen; nuclear compartmentalization, however, was much lower (approximately 20%) than in other cultures. In vitro reconstitution studies, combining 3H-R1881-loaded cytosol with naive nuclei, lead us to suggest that the defect in nuclear compartmentalization lies at the level of the nuclear acceptor site rather than the cytoplasmic binder in affected cells. We interpret the data to suggest that defective nuclear binding of AR complexes may be involved in a proportion of cases of abnormal development of the external genitalia.

Adolescent↗
PubMed1983

Progesterone receptors in rat thymus.

Tritiated promegestone ([3H]R5020) is bound with high affinity in cytosol prepared from the thymus gland of both male and female rats. To prevent tracer binding to glucocorticoid receptors, we have used excess RU26988 (11 beta, 17 beta-dihydroxy-21-methyl-17 alpha-pregna-1,4,6-trien-20-yn-3-one), a highly specific synthetic glucocorticoid. In the presence of 1 microM RU26988, [3H]R5020 was bound with high affinity (Kd less than or equal to 1 nM) and specificity (R5020 greater than progesterone much greater than estradiol greater than dihydrotestosterone = cortisol = corticosterone = dexamethasone) appropriate for progesterone receptors (PR). These sites were predominantly located in the epithelioid fraction of the thymus. PR levels were 14 +/- 3 fmol/mg protein in female thymus and 10 +/- 4 fmol/mg in male thymus; estrogen administration elevated thymic PR levels in both species (female, 26 +/- 2 fmol/mg; male, 21 +/- 3 fmol/mg). In estrogen-primed female rats, cytosolic thymic PR levels were acutely lowered to 20% of estrogen-primed control levels by the im administration of 1 mg progesterone. Thymic PR levels in pregnant (11-14 days) rats were approximately 50% of those in nonpregnant controls. Effects of glucocorticoids, androgens, and estrogens on the thymus are well documented; the demonstration of PR raises the possibility of direct effects of progesterone on the thymus.

Androstanols↗
PubMed1983

Dexamethasone induces different cellular protein synthetic responses in PNA+ and PNA- mouse thymocyte subpopulations.

Thymocytes from adrenalectomized BALB/c male mice were separated by peanut agglutination (PNA) into cortical, corticosensitive, PNA+ cells and larger, medullary, corticoresistant, PNA- cells; the extent of cross-contamination of PNA+ and PNA- cells, and vice versa, was checked by flow microfluorometry. Glucocorticoid receptor profiles were established with 3H-dexamethasone as probe; no differences in receptor affinity or cellular concentration, or in cytoplasmic and nuclear compartmentalization were seen between PNA+ and PNA- cells. On two-dimensional gel electrophoresis, PNA+ and PNA- thymocytes from oil-injected (control) adrenalectomized mice showed patterns of incorporation of 35S-methionine into protein that differed in at least 12 spots, as revealed by autoradiography. PNA+ and PNA- cells from mice treated with submaximal (6 micrograms/day) or near-maximal thymolytic doses of dexamethasone (20 micrograms/day) were also examined by two-dimensional gel electrophoresis. Both PNA+ and PNA- cells showed substantial, overlapping dexamethasone-induced changes in protein synthetic profiles.

Animals↗
PubMed1982

Dysgerminoma--gonadoblastoma and familial 46XY pure gonadal dysgenesis: case report and review of the genetics and pathophysiology of gonadal dysgenesis and H-Y antigen.

46XY gonadal dysgenesis is a rare condition of intersexuality first described in detail by Swyer in 1955. It is characterized by a phenotypic female who is tall, eunuchoid with normal female external genitalia, hypoplastic uterus and Fallopian tubes, streak ovaries and primary amenorrhoea. The patients exhibit none of the associated congenital defects such as webbing of the neck and genu valgum seen in Turner's syndrome. Although rare, this clinical entity is important to recognize because of the high incidence of gonadoblastomas and subsequent development of dysgerminoma. The condition may be familial and therefore siblings need to be screened. To the geneticists and scientists researching in the area of intersexuality, hermaphroditism and sexual determination, it has helped to unveil the mechanisms of gonadal and genital sexual development.

Adolescent↗
PubMed1982

Differences in proteins synthesized by fibroblasts from normal individuals and patients with complete testicular feminization.

Patterns of protein synthesis by genital skin fibroblasts from three unrelated normal individuals and three unrelated patients with complete testicular feminization were compared to two-dimensional gel electrophoresis. cell lines were maintained in monolayer culture and pulse labeled with [35S]methionine. Cells were lysed in 9 M urea, and aliquots of 20 microliters subjected to isoelectric focussing and polyacrylamide gel electrophoresis followed by autoradiography. Gels of control fibroblasts showed two proteins (mol wt approximately 45,000, approximately 85,000; pKi approximately 5.0) markedly more prominent than on gels from affected fibroblasts. This pattern was unaltered by prior exposure to dihydrotestosterone, suggesting differences in constitutive proteins of the fibroblast cells. Parallel studies demonstrated a marked reduction in the ability of fibroblasts from patients with complete testicular feminization to bind androgens in vitro compared with those of normal individuals. The relationship between these proteins, androgen receptors, and androgen insensitivity requires further investigation.

Androgen-Insensitivity Syndrome↗
PubMed1982

Glucocorticoid and mineralocorticoid effects on adrenocorticotropin and beta-endorphin in the adrenalectomized rat.

Immunoreactive ACTH (ir-ACTH) and immunoreactive beta-endorphin (ir-betaEP) were determined in plasma, anterior pituitary, neuro-intermediate lobe, and hypothalamus of sham-adrenalectomized rats, and adrenalectomized rats given six daily injections of vehicle (oil), dexamethasone, 9alpha-fluorocortisol or deoxycorticosterone. 6 d after adrenalectomy, anterior pituitary ir-ACTH and ir-betaEP were double, and plasma levels approximately fivefold those in controls. Adrenalectomy did not alter hypothalamic levels of either peptide, or ir-betaEP in neuro-intermediate lobe, in which tissue ir-ACTH was below detection limit at routine dilutions. Dexamethasone (0.2-200 mug/d) concurrently suppressed plasma ir-ACTH and ir-betaEP, with a near maximal effect at 20 mug, and a half-maximal effect between 2 and 6 mug; similar dose-response characteristics were found for thymolysis. Step-wise increases in anterior pituitary content of both peptides were found, with no change in hypothalamic levels of either peptide, or neuro-intermediate lobe ir-betaEP. 9alpha-fluorocortisol (0.2-200 mug/d) produced plasma, anterior pituitary, and hypothalamic effects equivalent to dexamethasone, but with one-tenth the potency. Unlike dexamethasone, higher doses of 9alpha-fluorocortisol significantly elevated neuro-intermediate lobe ir-betaEP. Deoxycorticosterone (2-2,000 mug/d) produced no significant changes in plasma, anterior pituitary or hypothalamic levels of either peptide; like 9alpha-fluorocortisol, doses of >60 mug/d significantly elevated neuro-intermediate lobe ir-betaEP. Whereas ir-ACTH and ir-betaEP synthesis in and release from the anterior pituitary are under complex negative feedback glucocorticoid control, there exists a mineralocorticoid-specific effect on neuro-intermediate lobe content of ir-betaEP.

Adrenal Glands↗
PubMed1982

Mineralocorticoid and glucocorticoid effects on 31,000- and 29,000-dalton proopiomelanocortin in rat anterior pituitary and neurointermediate lobe.

The effects of adrenal steroids on proopiomelanocortin (POMC) levels in rat pituitary have been studied by two-dimensional gel electrophoresis. In intact rats the relative abundance of POMC was much higher in the neurointermediate lobe (N-IL) than in anterior pituitary (AP); in both tissues the predominant species appeared to be of 29,000-dalton (29K) molecular mass, with lesser amounts of a 31K form. In both tissues, the 31K and 29K forms showed multiple spots, consistent with different degrees of sialoglycosylation. Adrenalectomy was followed by a marked increase in AP levels of POMC, and a marked decrease in N-IL levels. In adrenalectomized rats, dexamethasone administration did not affect N-IL levels of POMC, but suppressed 35S incorporation into POMC in AP in a dose-related manner; deoxycorticosterone showed minimal effects on AP levels of POMC, but progressively elevated N-IL levels; 9 alpha fluorocortisol (9 alpha fF) progressively both suppressed AP levels, and raised N-IL levels of POMC. Estimation of immunoreactive (ir) ACTH and ir-beta-endorphin in parallel samples showed an elevation of N-IL levels in response to mineralocorticoids (deoxycorticosterone, 9 alpha fF), and a paradoxical elevation of AP levels in response to glucocorticoids (dexamethasone, 9 alpha fF) compared with oil-injected adrenalectomized controls. We conclude (a) that glucocorticoids suppress the secretion of ir-ACTH and ir-beta-endorphin to a greater extent than they inhibit the synthesis of POMC; (b) that mineralocorticoids specifically elevate the N-IL levels of both POMC and its immunoreactive product (beta-endorphin).

Adrenocorticotropic Hormone↗
PubMed1982

Dihydrotestosterone and estradiol deplete corticosensitive thymocytes lacking in receptors for these hormones.

The sex steroids dihydrotestosterone (DHT) and estradiol (E2), were found to deplete the same cortical population of thymocytes as the glucocorticoid dexamethasone (DM) in intact and in adrenalectomized, castrated mice. Although receptors for DM were demonstrated in this cortical population, none were found for E2 or DHT. We suggest that the sex steroids bind to other thymic elements, possibly thymic reticular epithelial cells, which may in turn act secondarily on cortical thymocytes, or their precursors within the thymus.

Animals↗
PubMed1981

Androgens and the thymus.

Tritiated dihydrotestosterone ([3H]DHT) binds with high affinity to a single class of limited capacity sites in cytoplasmic preparations from rat and mouse thymus glands. The affinity of these bindings sites for [3H]DHT (Kd at 4 C, 1 nM) and their specificity [methyltrienolone (R1881) greater than DHT greater than testosterone much greater than estradiol = progesterone greater than promegesterone (R5020) much greater than aldosterone = cortisol] are characteristic of androgen receptors in classical target tissues. The affinity of thymic androgen receptors for [3H]DHT did not differ with age, sex, or species; the concentration of androgen receptors was higher in males than females and higher in older compared with younger animals. Castration of male mice was followed by marked (approximately 2-fold) thymic hypertrophy; the concentration of androgen receptors fell to approximately one third the control value as a function of organ weight, but did not change significantly as a function of thymic DNA. Chronic administration of DHT (200 micrograms/day) did not alter thymic weight or androgen receptor levels in intact male mice. In castrate mice, however, the administration of 200 micrograms DHT completely abolished the thymic hypertrophy otherwise seen post castration and significantly increased the total thymic content of androgen receptor. The administration of dexamethasone (0.6-60 micrograms/day for 5 days) caused dose-related thymolysis; on a weight basis, the concentration of androgen receptor rose markedly, suggesting that androgen receptors are confined to the subpopulation of thymocytes relatively resistant to glucocorticoids.

Aging↗
PubMed1976

Binding of thyroid microsomes by lymphocytes from patients with thyroid disease and normal subjects.

Lymphocytes that could bind 125I-labelled thyroid microsomal membranes (ABL) were present in the peripheral blood of patients with various types of thyroid disease as well as in normal healthy subjects. In patients with anti-thyroid cytoplasmic antibodies the number of ABL was about three times normal (11-21 +/- 0-60 compared with 3-26 +/- 0-18 per 10(4) lymphocytes). In contrast, in patients with thyroid disease without anti-thyroid cytoplasmic antibodies, the number of antigen-binding lymphocytes was not significantly greater than in the normal controls (3-94 +/- 0.14 per 10(4) lymphocytes). The binding of thyroid microsomes by antigen-binding lymphocytes could be blocked by thyroid microsomes but not by thyroid mitochondrial membranes, thyroglobulin or liver microsomes.

Autoantibodies↗
PubMedDate not supplied

Effects of naloxone, glycyrrhizic acid, dexamethasone and deoxycorticosterone in repetitive stress.

1. The present study examined the effect of naloxone (NAL), glycyrrhizic acid (GCA), deoxycorticosterone (DOC) and dexamethasone (DEX) on daily repeated 2 h chronic restrained stress (RS) on the locomotor activity (LA) of rats tested in the open field arena to elucidate the possible roles of opioids, glucocorticoids and mineralocorticoids in response to stress. 2. Intact and adrenalectomized (ADX) rats were either injected with 0.1 mL of NAL (0.32 microgram/100 g BW), 2.4 mg/kg DOC or 120 micrograms/kg DEX or had 1.0 mg/mL GCA dissolved in their drinking water or normal saline (for the ADX group) dissolved in their drinking water. 3. In intact groups, treatment with NAL completely blocked the stress response and treatment with GCA, DOC and DEX partially prevented the stress response. Adaptation occurred on either days 4, 5, 6 or 7 for intact rats treated with DEX, DOC, GCA or control rats, respectively. All ADX control rats died following the first 2 h RS. Adrenalectomized rats treated with DEX or DOC adapted later compared with intact rats, while rats given either GCA or NAL were unable to block or adapt to chronic RS. 4. These findings demonstrate that the stress response is primarily mediated by endogenous opioids, in that it is blocked by NAL. Both mineralocorticoids and glucocorticoids, which can act centrally to inhibit endorphins, partially blocked the stress response. The effect of GCA in intact rats was similar to that of both DEX and DOC in intact rats. Adrenalectomized rats treated with GCA (despite their lack of endogenous corticosterone) showed a stress response that was significantly different from the other ADX groups, implying that GCA had effects independent of endogenous corticosterone.

11-beta-Hydroxysteroid Dehydrogenases↗