Search PubMed⌕ Search

Biomedical subjects

J Crabbe

Publications and source records attributed to J Crabbe.

At least 37 records · Page 2Linked to original sources
PubMed1987

Altered interaction between triiodothyronine and its nuclear receptors in absence of cortisol: a proposed mechanism for increased thyrotropin secretion in corticosteroid deficiency states.

Thyroid hormones occasionally appear less effective when administered alone to patients with panhypopituitarism, and manifestations suggestive of hypothyroidism have been reported in patients suffering from untreated Addison's disease. In the latter condition, thyrotropin secretion is increased: this occurs already after as little as 2 days of temporary withdrawal of therapy with substitution doses of corticosteroids while circulating levels of thyroid hormones remain within normal limits. Therefore, a possible role of cortisol in interaction between triiodothyronine and its nuclear receptors was examined at the level of circulating lymphocytes obtained from patients with primary or secondary adrenocortical failure. The affinity of these receptors was found to be decreased, by more than 50% on average, in the absence of cortisol treatments. This change was promptly corrected upon resumption of therapy. The number of binding sites was not significantly modified. The influence of cortisol on thyroid hormone receptors discussed here might account for the clinical observations mentioned above.

Addison Disease↗
PubMed1987

Addison's disease: immunological aspects.

The frequency of HLA DR3 in patients with Addison's disease is increased and the relative risk factor rises to 10 when adrenocortical failure is part of a polyendocrinopathy.

Addison Disease↗
PubMed1987

Erythrocyte aldehyde dehydrogenase, plasma chlorpropamide concentrations and the chlorpropamide alcohol flush.

Erythrocyte aldehyde dehydrogenase activity (EALDH) was measured in 21 diabetics on long-term chlorpropamide therapy. Median EALDH was 0.362 units, range 0.108 to 0.750 units and correlated neither with previously assessed chlorpropamide alcohol flushing nor with coincident plasma or erythrocyte chlorpropamide concentration. The hypothesis that genetic or permanently acquired reduction in EALDH correlates with CPAF status was not supported. There was no concentration-related inhibition of the enzyme by prevailing plasma or erythrocyte chlorpropamide.

Alcohol Drinking↗
PubMed1986

Enhanced 17 alpha-hydroxylation of pregnenolone and increased androgen production by rabbit adrenocortical cells stimulated chronically with corticotropin.

The postulated chronic stimulatory effect of corticotropin (ACTH) on pregnenolone production and on 17 alpha-hydroxylase activity was evaluated on adrenocortical cells obtained from control and chronically ACTH-treated rabbits. The cells were incubated with various concentrations of ACTH added alone or together with trilostane, so as to inhibit further conversion of pregnenolone and dehydroepiandrosterone. The maximal steroidogenic effect of ACTH (determined in the absence of trilostane) was increased 2-fold in adrenocortical cells from ACTH-treated animals; furthermore, cortisol production was increased whereas that of corticosterone decreased. While the generation of pregnenolone was of comparable magnitude for cells from both experimental groups, chronic in vivo treatment with ACTH was followed by a 40-fold enhancement in 17-hydroxypregnenolone production. Concomitantly, maximal DHEA production documented in the presence of ACTH and trilostane was enhanced more than 200-fold, from 0.45 +/- 0.20 pmol in control rabbits to 147 +/- 67 pmol in cells from ACTH-treated animals. The corresponding values of DHEA-sulphate production were 0.86 +/- 0.12 and 432 +/- 334 pmol, respectively. Thus, a prolonged stimulatory effect of ACTH on rabbit adrenocortical cells consists in an enhancement of the capacity to generate pregnenolone, and to convert this compound into 17-hydroxylated steroids.

17-alpha-Hydroxypregnenolone↗
PubMed1986

Use of chromosomally mapped and identified mouse brain proteins for behavioral genetic analysis of alcoholism.

A logical first place to look in order to identify loci determining behavioral differences between inbred and certain outbred strains of mice is among the proteins expressed in brain. Fourteen mouse brain proteins have been demonstrated to be genetically variant, four of these have been chromosomally mapped and an additional twelve have been identified and can be simultaneously screened by two dimensional electrophoresis. Certain genetic differences in behavior relevant to alcohol consumption and the effects of alcohol occur between inbred, recombinant inbred and selectively outbred strains. Two genetic correlations are reported, one between an isoelectric point variant of A7 (a 71 kd, pI 5.4 abundant protein) and resistance to signs of ethanol withdrawal and the other between A12 (a 28 kd, pI 5.6 protein) and ethanol intake. Though tentative, these findings illustrate the power of this approach for behavioral genetic analysis and may allow the biochemical genetic bases of these traits to be understood.

Alcoholism↗
PubMed1985

Enhanced androgen production by rabbit adrenocortical cells stimulated chronically with corticotropin: evidence for increased 17 alpha-hydroxylase activity.

The effects of prolonged treatment with corticotropin (ACTH1-24, 200 micrograms s.c. daily during 12 days) on the production of androgens and glucocorticoids were studied on rabbit dispersed adrenocortical cells. The steroidogenic capacity of adrenocortical cells, expressed in terms of the maximal response to ACTH of glucocorticoid (i.e. corticosterone and cortisol) production, was significantly increased after treatment with ACTH. This was associated with a loss of sensitivity to this peptide: indeed, the concentration of ACTH required to induce a half maximal secretory response was one order of magnitude higher with cells from ACTH-treated animals. Among the C21 steroids measured the changes observed involved the 17 alpha-hydroxylated compounds (cortisol, cortisone, 11-deoxycortisol) while corticosterone production was significantly depressed. This effect of prolonged ACTH treatment on steroidogenic pathways involving 17 alpha-hydroxylation, was further evidenced by a clear-cut enhancement in androgen secretion (dehydroepiandrosterone, androstenedione and testosterone) by adrenocortical cells from ACTH-treated animals. The changes observed after treatment of the animal with ACTH were equally obvious, whether the adrenocortical cells were incubated with ACTH or with dibutyryl-c-AMP.

Adrenal Cortex↗
PubMed1985

Mechanism of inhibition by lithium of sodium transport in the toad bladder.

Lithium transport across the urinary bladder of Bufo marinus has been studied by means of the short-circuit current technique, as well as unidirectional ion flux measurements. Exposure to lithium of the epithelial (mucosal) surface of this preparation led to a slow, progressive decrease of ion transport, with increasing discrepancy between short-circuit current and lithium influx; in fact there was still an appreciable lithium influx across bladder exposed to amiloride even though short-circuit current was suppressed. Ohmic conductance and sodium efflux barely increased under these circumstances. Upon replacement of lithium by sodium on the epithelial side, the preparations recovered slowly indeed, and residual lithium could be detected in bladder tissue for more than 2 hr while the rate of sodium extrusion at the basal-lateral cell border was slowed down. Recovery from exposure to lithium was accelerated by vasopressin and amphotericin, both of which facilitate sodium entry at the apical border of the epithelium. Thus the lasting deleterious influence of lithium on sodium transport might result from the fact that this ion, once trapped in the cytoplasm, closes the sodium channels.

Amiloride↗
PubMed1984

The autoxidation of glyceraldehyde and other simple monosaccharides under physiological conditions catalysed by buffer ions.

Glyceraldehyde and other simple monosaccharides autoxidise under physiological conditions generating 1-hydroxyalkyl (carbon-centred) free radicals and intermediates of dioxygen reduction: superoxide, hydrogen peroxide and hydroxyl radicals. The major glyceraldehyde-derived product is the alpha-ketoaldehyde, hydroxypyruvaldehyde. Close similarities between the temperature dependence of the kinetics of glyceraldehyde autoxidation and glyceraldehyde enolisation to an ene-diol indicates that enolisation is the rate-determining step in the autoxidative process. Inspection of a wide range of carbonyl compounds showed that the monosaccharide moiety -CH(OH)-C- is conserved in carbonyl compounds reactive towards autoxidation, indicating that the ability to form an ene-diol is a prerequisite to monosaccharide autoxidation. The ene-diol intermediate autoxidises rapidly to the products: hydrogen peroxide, water and alpha-ketoaldehydes: beta-hydroxypyruvaldehyde is produced from glyceraldehyde and dihydroxyacetone, glyoxal from glycolaldehyde autoxidation. Ene-diol autoxidation is catalysed by hydrogen peroxide and trace metal ion contaminants; removal of either of these factors sufficiently retards ene-diol autoxidation such that ene-diol autoxidation rather than enolisation becomes the rate determining step in the overall autoxidative process. Under enolisation control, the rate of monosaccharide autoxidation is influenced by pH and the buffer system used for pH control.

Animals↗
PubMed1978

Serum Neurophysins in familial central diabetes insipidus.

Antibovine neurophysin antibodies (anti-bNpI and/or anti-bNpII) are present in certain patients with familial central diabetes insipidus; these are exogenous origin, as they are not present in patients who have not received treatment with crude posterior pituitary extracts over the years preceding the analysis. Immunoreactive neurophysins were detectable in the blood of five patients with familial central diabetes insipidus, and in two of them, the levels increased after a short period of water restriction. There is marked polymorphism of these neurophysins from one serum to another: neurophysin I was consistently absent, while neurophysin II, accessory neurophysins, and other immunoreactive substances not present in normal sera were sometimes present in variable amounts. Immunoreactive AVP was undetectable in the urine of all patients, while immunoreactive OT was found in three of them; the latter substance could, however, be arginine vasotocin. Data are presented suggesting that the association between the biosynthesis of neurophysin I and AVP on the one hand, and neurophysin II and OT on the other hand is maintained in patients with isolated AVP deficiency on the basis of a congenital defect.

Adolescent↗
PubMedDate not supplied

Characteristics of the response of human adrenocortical cells to ACTH.

The effects of adrenocorticotrophic hormone (ACTH) on human adrenocortical steroidogenesis were studied in adrenocortical cells which had been isolated from normal and hyperplastic glands by a technique combining tyrpsin digestion and mechanical dispersion, and incubated in the presence of ACTH or dibutyryl cyclic AMP (dbcAMP). The response was measured in terms of cyclic AMP, cortisol, corticosterone, 11-deoxycortisol and cortisone production. A classical sigmoid curve, calculated by non-linear, least square method, related the increase in cAMP production or in steroidogenesis to the log dose of ACTH. For the normal adrenocortical cells, the estimated concentration of ACTH inducing a half-maximal response was approximated 2h0 pg ACTH 1-24/ml for steroidogenesis, against 437 pg/ml for cAMP production. The estimated Vmax (per 107 cells/ml, on average) was 27 pmol cAMP/2 and for steroidogenesis (in ng/2 h): 188 for cortisol, 106 for corticosterone, 37 for 11-deoxycortisol, and 32 for cortisone, dbcAMP (1.0 mM) stimulated steroidogenesis to a comparable extent. The cells from a hyperplastic adrenal gland exhibited a steroidogenic response to ACTH and dbcAMP which was 2-3 times greater than the response of a similar number of normal adrenocortical cells. Calculated per pmol cAMP generated, the ACTH-stimulated cortisol production by cells from hyperplastic gland was also increased with respect to normal cell response. These data suggest a prolonged effect of ACTH on cortisol biosynthetic pathway beyond the membrane step of cAMP generation.

Adrenal Cortex↗