Search PubMed⌕ Search

Biomedical subjects

S Brody

Publications and source records attributed to S Brody.

At least 91 records · Page 5Linked to original sources
PubMed1987

Adrenal steroids in post-menopausal women: relation to obesity and to bone mineral content.

Basal levels and ACTH-induced increments of serum 17 alpha-hydroxyprogesterone (170HP), cortisol, 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were related to the degree of obesity and to trabecular bone mineral density in 29 postmenopausal women. The ACTH-induced increment of 170HP (delta 170HP) was negatively correlated to basal DHA and delta DHA. Positive correlations were found between obesity, expressed as Broca's index, and delta DHA and the delta DHA/delta 170HP ratio. Bone mineral density was positively correlated to basal DHAS, delta DHA, delta DHAS and the delta DHA/delta 170HP ratio, and negatively correlated to delta 170HP. DHA and 170HP represent a crossroad in adrenocortical steroid biosynthesis, leading to delta 5-androgens and glucocorticoids as main products. Besides age, obesity may also influence the intra-adrenal distribution between these two main steroidogenic pathways. The results suggest that differences at a very early stage of the adrenal steroidogenesis may influence calcium homeostasis in the post-menopausal woman.

Adrenal Cortex Hormones↗
PubMed1987

High-dose estrogen-progestagen oral contraceptives: a risk factor for aneurysmal subarachnoid hemorrhage?

A 10-year follow-up (1970-79) of a defined general population (n = 159 200) of middle-aged (born in 1911-40), urban, native Swedes, revealed that the prevalence rate of subarachnoid hemorrhage was 2.8 times higher in females than in males. This was mainly due to an accumulation of non-hypertensive aneurysmal subarachnoid bleeds in women born in the period 1932-40. The cases were significantly (P less than 0.001) overrepresented among divorced women, with relative risks of 1.89, 0.98 and 0.63 for divorced women, married women and spinsters (never married), respectively. Since high-dose estrogen-progestagen oral contraceptives have largely been used by the younger members of this study cohort, it may be speculated whether the observed substantial excess prevalence rate of subarachnoid hemorrhage with saccular aneurysm, not reported previously, represents a cohort effect unexpected after the introduction of low-dose oral contraceptives.

Adult↗
PubMed1987

Serum sex hormone binding globulin (SHBG), testosterone/SHBG index, endometrial pathology and bone mineral density in postmenopausal women.

Serum levels of sex hormone binding globulin (SHBG) and testosterone (T) and bone mineral density (BMC) in the non-dominant forearm were determined in 28 postmenopausal women aged 44-62 years. Significant correlations (Spearman's rank correlation test) were found between BMC and SHBG (negative) and between BMC and the T/SHBG index on biologically active androgen (positive). Significant correlations were also found between endometrial pathology (Kruskal-Wallis test; 0 = atrophic, 1 = hyperplasia, 2 = cancer) and SHBG (negative) and the T/SHBG index (positive). It is suggested that SHBG may act as one common denominator in the pathogenesis of postmenopausal osteoporosis and endometrial disease by regulating the levels of unbound, biologically active androgens and estrogens.

Adult↗
PubMed1986

Circadian rhythms in Drosophila melanogaster: analysis of period as a function of gene dosage at the per (period) locus.

Mutations at the per (period) locus of Drosophila melanogaster affect the period of its circadian rhythms. An analysis of published data on strains having duplications and deletions of the per locus indicates that the period is a logarithmic function of the level of the per gene product. The analysis also indicates that period is relatively insensitive to the level of that gene product; a presumed 300% increase in the gene product level produces only a 4.6% decrease in the period. The period of a strain transformed with per+ DNA conforms to the same logarithmic relationship if the level of mRNA in the transformant, which is one-tenth that in the wild type, is considered equivalent to a gene dosage one-tenth the wild type dose of 2, or 0.2. The periods of strains having various doses of mutant per alleles which shorten (pers) or lengthen (per1) the period can be fitted to the same logarithmic function. The analysis may provide an explanation for the partial dominance of pers over per+ and the dominance of per+ over per1, since it suggests that the per1 gene product is nearly inactive while the pers gene product is more than 34 times as active as the wild type product. Analysis of periods of strains heterozygous at the per locus suggests that the per gene product may be a multimeric protein. Three possible roles for the per gene product in circadian rhythmicity are discussed, including a role in synchronizing rhythm-producing cells.

Alleles↗
PubMed1986

Neurospora crassa mitochondria contain two forms of a 4'-phosphopantetheine-modified protein.

When Neurospora crassa was labeled with [14C]pantothenic acid during growth, the mitochondrial fraction contained two bands of radioactivity of Mr 19,000 and 22,000 by sodium dodecyl sulfate gel electrophoresis. The 19-kDa band was converted to the 22-kDa band by four treatments which are characteristic of the cleavage of a thioester bond: dithiothreitol and 2-mercaptoethanol at basic but not neutral pH, alkaline methanolysis, sodium borohydride in tetrahydrofuran, and hydroxylamine at neutral pH. Mitochondrial subfractionation indicated that the 22-kDa form was preferentially associated with the soluble fraction while the 19-kDa form was found in all fractions. Several properties of the mitochondrial protein were similar to the Escherichia coli acyl carrier protein: Mr on sodium dodecyl sulfate gels, decreased electrophoretic mobility under deacylating conditions, isoelectric point, and covalent attachment of 4'-phosphopantetheine. The 19- and 22-kDa bands may therefore represent acylated and deacylated forms of a mitochondrial acyl carrier protein.

Acyl Carrier Protein↗
PubMed1985

The kinetics of changes in the fatty acid composition of Neurospora crassa lipids after a temperature increase.

The fatty acid composition of the total lipids, phospholipids and neutral lipids of log-phase shaker cultures of the bd (band) strain of Neurospora crassa, were measured every 2 h for an 8-h period following a temperature increase from 22 to 40 degrees C. For purposes of comparison, the fatty acid composition was also measured when cultures were grown from inoculation at temperatures between 22 and 40 degrees C. In the phospholipids, the temperature jump produced, over a 4-6 hour span, a linear decrease in the linolenic acid (18:3) content from 31 to 10 mol% and an increase in the linoleic acid (18:2) content from 41 to 45 mol% for a few hours, followed by a decrease to 38 mol%. The oleic acid (18:1) content increased, after a 2 h lag, from 5 to 26 mol%. The temperature increase caused a decrease in the double bond index from 180 to 135 but produced no changes in the mol% of the saturated fatty acids, the ratio of saturated to unsaturated fatty acids, the total amount of fatty acids per gram dry weight, or the growth rate of the cultures. After the switch to 40 degrees C the total amount of 18:3 per flask increased only slightly over the 8 h period, indicating that there was little loss of 18:3 from the mycelia by beta-oxidation, or by conversion to other fatty acids. Since the mass of the culture increased some 4-fold in this time, it suggests that the decrease in the mole percent of 18:3 is probably due to a decrease in the rate of synthesis of 18:3.

Fatty Acids↗
PubMed1985

A pantothenate derivative is covalently bound to mitochondrial proteins in Neurospora crassa.

The presence of protein-bound pantothenate in Neurospora crassa was investigated by labelling a pantothenate auxotroph (pan-2) with [14C]pantothenate and examining mycelial homogenates on dodecyl sulfate/polyacrylamide gels. Five peaks of radioactivity were found, with apparent molecular masses of 200, 140, 22, 19, and 9 kDa. The 200-kDa peak was identified as fatty acid synthetase, based on its absence in a fatty acid synthetase mutant. The 22-kDa and 19-kDa peaks co-purified with mitochondrial markers on sucrose gradients. When purified mitochondria were fractionated, the 19-kDa protein was associated with the inner membrane and the 22-kDa protein was enriched in the soluble mitochondrial fraction. The label was quantitatively recovered from the mitochondrial proteins as 4'-phosphopantetheine after mild alkaline hydrolysis. Although the function of this post-translational modification of mitochondrial proteins is not known, several possibilities are discussed: the 4'-phosphopantetheine may act as a carrier group in an enzymatic reaction, or it may perform a regulatory function as part of an enzyme complex.

Centrifugation, Density Gradient↗
PubMed1985

Circadian rhythms in Neurospora crassa: the effects of point mutations on the proteolipid portion of the mitochondrial ATP synthetase.

Five oligomycin-resistant (olir) mutant strains of Neurospora crassa were analyzed for their growth rate and for the periodicity of their circadian rhythm. The most resistant strains had periods of 18-19 h while the least resistant strain had a normal period of 21.0 h. There was a rough correlation between the in vivo degree of oligomycin-resistance and the amount of change in the period. Several of the olir mutations have been previously described by Sebald et al. (1977) in terms of known amino acid changes in the primary structure of the proteolipid, or DCCD-binding protein, found in the F0 membrane portion of the mitochondrial ATP synthetase. Amino acid changes in the structure of this protein are reported here for two other olir mutations. The proteolipid isolation procedures were slightly modified to include a delipidation step, and an HPLC procedure was developed to separate the hydrophobic peptides of this protein. Analysis of heterocaryons carrying both the olir and olis markers indicated that the olir and olis mutations were codominant to each other in terms of period and growth rate. The changes in the primary structure of this DCCD-binding protein reported here are the first known examples of changes in the primary structure of a protein which alter the period of a circadian rhythm.

Chromatography, High Pressure Liquid↗
PubMed1985

Circadian rhythms in Neurospora crassa: interactions between clock mutations.

Mutations at four loci in Neurospora crassa that alter the period of the circadian rhythm have been used to construct a series of double mutant strains in order to detect interactions between these mutations. Strains carrying mutations at three of these loci have altered periods on minimal media: prd-1, several alleles at the olir (oligomycin resistance) locus and four alleles at the frq locus. A mutation at the fourth locus, cel, which results in a defect in fatty acid synthesis, also leads to lengthening of the period when the medium is supplemented with linoleic acid (18:2). The cel mutation was crossed into strains carrying the frq, prd-1 and olir mutations, and the periods of the double mutant strains with and without 18:2 supplementation were determined. In addition, data from the literature for other combinations of loci and/or chemical effects on the period have been reanalyzed.--It was found that both prd-1 and olir are epistatic to the effects of 18:2 on cel; in the series of cel frq double mutant strains, the period-lengthening effect of 18:2 is inversely proportional to the period of the frq parent, indicating an interaction between frq and cel; period effects reported in the literature can be described as changes by a fixed ratio or percentage of the period rather than by a fixed number of hours, and the data, therefore, can support a multiplicative as well as an additive model.--Several biochemical interpretations of these interactions are discussed, based on simple chemical kinetics, enzyme inhibition kinetics and the control of flux through metabolic pathways.

Circadian Rhythm↗
PubMed1984

A comparison of two methods for detecting hormone peaks: the effect of sampling interval on gonadotropin peak frequency.

There is no consensus on the optimum method to identify gonadotropin pulses in serum. We compared two approaches for detecting gonadotropin peaks. The first employed the conventional criterion of an increment from nadir to peak of 3 times the intraassay coefficient of variation (3 CV). The second identified peaks by Student's t test to quadruplicate measurements at each time point. We obtained blood samples every 5 min for 6 h from four women in the follicular phase. We also constructed control or noise series by subdividing single serum pools into consecutively labeled aliquots. Any variations in hormone concentration in the noise series that were identified as peaks were, by definition, false positive peaks. We evaluated the effect of sampling interval on gonadotropin peak detection by omitting data to simulate sampling every 10, 15, or 20 min. The 3 CV approach identified numerous false positive peaks in the noise series and detected as many peaks in the noise series as it did in the patient series. Increasing the sampling frequency from every 20 to every 5 min nearly doubled the apparent peak frequencies in both the patient and the noise series (P less than 0.025). By contrast, the t test method detected far fewer false positive peaks and significantly more peaks in the patient series than in the noise series. Increasing the sampling frequency from every 20 to every 5 min resulted in a 50-75% increase in peak frequency by the t test method. This increase in peak frequency appeared to result from improved detection of small peaks, because samples were obtained nearer the true peaks and nadirs. The resulting increase in the nadir to peak increment made it more likely that a small peak would achieve statistical significance. We conclude that increasingly stringent criteria for pulse detection should be applied as one increase the sampling frequency, and that the t test approach is a more valid method than the 3 CV approach because it yields significantly fewer false positive peaks.

Adolescent↗
PubMed1983

Levels of sulfhydryls and disulfides in proteins from Neurospora crassa conidia and mycelia.

Proteins extracted with 6 M guanidine at 90 degrees C from conidia (asexual spores) of Neurospora crassa contained ca. 25% more total protein thiol and a fivefold-higher content of disulfide bonds than proteins extracted from mycelia, as determined by labeling with iodo[14C]acetic acid. The total thiol content was 88 mumol/g of protein in conidia and 70 mumol/g of protein in mycelia. The level of protein disulfide was 18.5 mumol/g of protein in conidia and 3.5 mumol/g of protein in mycelia, by the iodo[14C]acetic acid labeling method. Confirmatory results were obtained with 5'5-dithio-bis-2-nitrobenzoic acid titration of protein thiol groups in 1% sodium dodecyl sulfate as well as by amino acid analysis of cysteic acid derivatives. Buffer-extracted proteins from conidia, but not mycelia, were found to contain enriched levels of protein thiols and disulfides per gram of protein as compared with guanidine hydrochloride extracts. It was demonstrated that the high disulfide content of crude conidial extracts was not due to measurable levels of mixed disulfides formed between protein sulfhydryl groups and cysteine. During germination of the conidia, the high disulfide levels of the conidial proteins remained constant. These data suggest that, unlike the disulfides of glutathione, the bulk of conidial protein disulfides were not reduced, excreted, or extensively degraded during germination.

Amino Acids↗
PubMed1983

Peripheral hormone levels and the endometrial condition in postmenopausal women.

Thirteen postmenopausal women with benign endometrial changes including proliferative, secretory and polypous endometrium, endometrial hyperplasia and atypia (group I) and 13 randomly selected age-matched controls with normal atrophic endometrium (group II) were studied with respect to serum levels of dehydroepiandrosterone (DHA) and its sulfate (DHAS), testosterone, total estrone, estradiol-17 beta, progesterone, FSH and prolactin. Serum levels of DHA, DHAS, testosterone and total estrone were significantly higher in group I than in group II; otherwise no significant differences were found. Mean values for body weight and for Broca's index, respectively, were almost identical in the two groups. It is speculated that the adrenal androgens may affect the endometrium in two ways, viz. via peripheral conversion to estrogens and/or via direct interaction with endometrial steroid receptors. The results give further support to the hypothesis of an association between adrenocortical hyperactivity and endometrial abnormalities including endometrial carcinoma.

Body Weight↗
PubMed1983

Serum levels of 4-androstene-3,17-dione in menstruating and postmenopausal women. Evaluation of a radioimmunoassay and correlation with bone mineral content and endometrial pathology.

A radioimmunoassay for serum 4-androstene-3,17-dione (A-4) using anti-4-androstene-3, 17-dione-11 alpha-hemisuccinate bovine serum albumin was applied to serum samples from 16 healthy, normally menstruating women in different phases of the menstrual cycle, from 36 healthy postmenopausal women and from 23 postmenopausal women with various bone mineral contents and endometrial conditions, undergoing an acute ACTH stimulation test. The values obtained in the normal subjects were consistent with those found in the literature. A-4 levels were significantly higher at midcycle than in the follicular phase and were significantly lower in postmenopausal than in menstruating women. ACTH increased the levels of A-4 significantly. However, no significant correlation was found between basal levels or the ACTH-induced increments of A-4 on the one hand and bone mineral content, endometrial condition and the patients' weight, age, or Broca's index on the other. This is in contrast to our previous finding of significant correlations between basal dehydroepiandrosterone sulfate and ACTH-induced increments in dehydroepiandrosterone on the one hand and bone mineral content on the other in the same clinical material. We discuss whether the differences in correlations to bone mineral content between the two adrenocortical androgens may be due to a rather more complex origin of the steroid moiety of A-4.

Adrenocorticotropic Hormone↗
PubMed1982

Adrenocortical steroids, bone mineral content and endometrial condition in post-menopausal women.

In 23 post-menopausal women, serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, unconjugated and total oestrone and prolactin were measured before and during an ACTH test. Significant positive correlations were found between basal levels of DHA and DHAS; DHA and unconjugated oestrone; DHA and total oestrone; testosterone and total oestrone and between unconjugated and total oestrone. ACTH significantly raised the levels of the steroids but not of prolactin. Significant positive correlations were found between basal levels and ACTH induced increments in DHA; between basal DHAS and increments in DHA and between increments in DHA and DHAS. A significant negative correlation was found between basal levels and increments in cortisol. No significant correlations were found between other combinations of hormone basal levels and/or increments. Significant positive correlations were found between basal levels of DHAS and the DHA response to ACTH respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also found between bone mineral content and pre-cancerous/cancerous state of the uterine epithelium. The results are a further support to the concept of a link between adrenal androgens and bone mineral density, and do also indicate a relation to endometrial pathology. The lack of correlation between cortisol and other steroids indicate different regulatory mechanisms. Prolactin does not seem to be involved in the regulation of the adrenal androgen synthesis.

Adrenal Cortex Hormones↗
PubMed1982

Circadian rhythms in Neurospora crassa: a mutation affecting temperature compensation.

The circadian rhythm of conidiation (spore formation) in Neurospora crassa is known to be temperature compensated, that is, the period is only slightly affected by the incubation temperature. Thus, the Q10 (the relative rate enhancement corresponding to a 10 degrees C rise in temperature) of the rhythm of the bd csp strain from 14 to 30 degrees C was 1.1, whereas the Q10 of the uncompensated growth rate in the same interval was 2.4. A mutation at the cel locus resulted in loss of the temperature-compensation property in cultures grown below 22 degrees C. The Q10 of the rhythm below 22 degrees C was 2.2, and periods of about 40 hr were observed. In contrast, the Q10 of the rhythm above 22 degrees C was 1.1, with circadian periods of 18-21 hr. Thus, cel displayed a threshold temperature or "break point" for the temperature compensation of its rhythm. Supplementation of cel strains, which require fatty acids, with unsaturated or short-chain fatty acids raised the threshold temperature to 26 degrees C, whereas supplementation with long-chain saturated fatty acids lowered it to 18 degrees C. These data suggest a role for fatty acids, as liquid components or as cellular metabolites, in the mechanism of temperature compensation.

Circadian Rhythm↗