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Biomedical subjects

B G Robinson

Publications and source records attributed to B G Robinson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Corticotrophin releasing hormone levels in human plasma and amniotic fluid during gestation.

OBJECTIVE: Corticotrophin releasing hormone, a hypothalamic neuropeptide also made in placenta, may regulate fetal maturation in a stress-responsive manner. The objectives of this study were: (1) to determine if levels of corticotrophin releasing hormone in the amniotic fluid correlate with fetal lung maturation; (2) to confirm that third trimester plasma levels of corticotrophin releasing hormone are increased in patients with pregnancy-induced hypertension compared to normotensives, and (3) to increase the recovery of extracted corticotrophin releasing hormone from plasma and amniotic fluid. DESIGN: (1) Levels of corticotrophin releasing hormone in amniotic fluid during the third trimester were compared with those of saturated phosphatidyl choline. (2) Corticotrophin releasing hormone levels were measured in a group of normotensive pregnant women during the entire gestation period. Corticotrophin releasing hormone levels during the third trimester were compared in normotensives and patients with pregnancy-induced hypertension. PATIENTS: Twenty-one non-pregnant normal volunteers and 63 pregnant women. MEASUREMENTS: Blood pressure, corticotrophin releasing hormone in plasma and amniotic fluid, and saturated phosphatidyl choline in amniotic fluid. RESULTS: Corticotrophin releasing hormone levels in amniotic fluid samples during the third trimester ranged from 12 to 98 pmol/l and positively correlated with the saturated phosphatidyl choline levels, but not with gestational age. A significant difference existed in plasma corticotrophin releasing hormone concentration between gestational age-matched third trimester normotensive and hypertensive gravids: corticotrophin releasing hormone levels were significantly lower in normotensives (223 +/- 65 pmol/l) than in patients with pregnancy-induced hypertension (544 +/- 106 pmol/l, P = 0.001). Plasma corticotrophin releasing hormone increased with gestational age from 51 pmol/l (range 8.4-85) at 25-32 weeks to 375 pmol/l (range 35-1386) at 33-40 weeks. During the third trimester the rise in plasma corticotrophin releasing hormone conformed to an exponential mathematical model of a positive feedback loop between placental corticotrophin releasing hormone and fetal adrenal cortisol. CONCLUSIONS: During the third trimester of pregnancy there is a positive correlation between the level of amniotic fluid corticotrophin releasing hormone and that of saturated phosphatidyl choline. The positive correlation between amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline, but not between amniotic fluid corticotrophin releasing hormone and gestational age, suggests that a factor(s), such as stress, may affect both amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline in parallel. Furthermore, our data are consistent with the hypothesis that the rise in placental corticotrophin releasing hormone is coupled to an increase in fetal glucocorticoid and lung maturation, and that stresses such as pregnancy-induced hypertension may accelerate this process.

Amniotic Fluid↗
PubMed1994

Effect of gold sodium thiomalate and its thiomalate component on the in vitro expression of endothelial cell adhesion molecules.

Endothelial adhesion molecules play an important role in the tissue recruitment of leukocytes in inflammatory conditions such as rheumatoid arthritis. We have investigated the effect of the antirheumatic drug gold sodium thiomalate on adhesion molecule protein and mRNA expression in cultured human endothelial cells. Gold sodium thiomalate inhibited cytokine (TNF, IL-1, IL-4)-stimulated expression of vascular cell adhesion molecule-1 and E-selectin but not intercellular adhesion molecule-1 on endothelial cells. Gold sodium thiomalate also suppressed TNF-stimulated increases in vascular cell adhesion molecule-1 and E-selectin mRNA levels but had no effect on intercellular adhesion molecule-1 mRNA. Thiomalate (mercaptosuccinate), but not gold thioglucose or D-penicillamine, mimics the effect of gold sodium thiomalate at equimolar concentrations. We propose that the inhibition of vascular cell adhesion molecule-1 and E-selectin expression by gold sodium thiomalate is due to its thiomalate and not its gold component. Gold sodium thiomalate has a direct effect on endothelial adhesion molecule expression, and this may contribute to its antiinflammatory activity.

Animals↗
PubMed1993

Secretory leucocyte proteinase inhibitor is produced by human articular cartilage chondrocytes and intervertebral disc fibrochondrocytes.

The objective of this study was to examine the expression of the secretory leucocyte proteinase inhibitor (SLPI) gene by human articular cartilage chondrocytes and intervertebral disc fibrochondrocytes. RNA was extracted from human articular cartilage chondrocytes, synovial fibroblasts and fibrochondrocytes of the annulus fibrosus. Expression was analysed by Northern blotting and hybridisation to a SLPI RNA probe. SLPI was isolated from chondrocyte culture supernatant by gel-permeation and cation-exchange chromatography and examined by a solid-phase enzyme-linked immunofiltration assay for SLPI and by SDS/PAGE using Western blotting with polyclonal IgG samples against bronchial mucus leucocyte proteinase inhibitor and SLPI. This identified biochemically and immunologically the major serine proteinase inhibitory protein synthesised by chondrocytes as SLPI. Secretory leucocyte proteinase inhibitor mRNA was detected in RNA preparations from articular cartilage chondrocytes and annulus fibrosus fibrochondrocytes. The results presented here allowed us to deduce that human articular cartilage chondrocytes and intervertebral disc fibrochondrocytes synthesized SLPI whereas human synovial fibroblasts did not.

Adult↗
PubMed1993

Renin messenger RNA, detected by polymerase chain reaction, can be switched on in rat atrium.

OBJECTIVE: The aim of the present study was to use a highly sensitive, polymerase chain reaction (PCR) technique to examine the controversial question of renin gene expression in the heart and to determine whether expression in cardiac tissue can be stimulated. DESIGN: The study involved female Wistar rats fed either a normal-sodium diet or a low-sodium diet, together with an angiotensin I converting enzyme inhibitor, enalapril, orally for 1 week. METHODS: RNA was extracted from atrium, ventricle, kidney (positive control) and submandibular gland (negative control) and, after reverse transcription into complementary DNA, was used in a 35-cycle PCR. Reaction products were visualized after electrophoresis by ethidium bromide staining and hybridization probing with [32P]-labelled target oligonucleotide. RESULTS: Atrial RNA from sodium-replete rats gave little or no renin messenger (m)RNA PCR product on ethidium bromide-stained gels. After DNA transfer, followed by hybridization probing and extended autoradiography, a faint band was seen. In sharp contrast, atrial extracts from sodium-depleted enalapril-treated rats displayed a pronounced band of hybridization, corresponding in size to that expected for renin mRNA. No band was seen for ventricle. CONCLUSION: The present PCR study has shown that in the normal sodium-replete rat, atrial tissue has only very low renin gene expression, but that after a low-sodium diet + treatment with enalapril, expression is switched on in atrium. Ventricular tissue does not express the renin gene in either state.

Animals↗
PubMed1993

Latina and African American women: continuing disparities in health.

Women of all races have faced incredible challenges as they sought to realize the promises of America. For women of color, these challenges were compounded by the second-class citizenship of U.S. racial and ethnic minority population groups. In an effort to assess the quality of life experienced by Latina and African American women, this article provides descriptive information on racial/ethnic differences in women's social conditions, health status, exposure to occupational and environmental risks, and use of health services. When possible, indices are stratified by family income to limit the effects of social class on the comparison of racial differences. The authors provide evidence that Latina and African American women are more likely than nonminority women to encounter social environments (e.g., poverty, densely populated neighborhoods, hazardous work conditions) that place them at risk for ill-health and injury. Although persistent racial disparities in health are often attributed to the lifestyle behaviors of racial minority populations, they are undoubtedly a consequence of poorer social conditions as well as barriers in access to quality health services. To achieve further gains, public policies must reduce social inequalities (i.e., by gender, race, and social class) and assure greater equity in access to resources that facilitate healthier environments and lifestyles. Public health initiatives should be community-based, reflecting a shared partnership that actively engages minority women in decision-making about their lives.

Adolescent↗
PubMed1992

The effect of insulin-induced hypoglycemia on gene expression in the hypothalamic-pituitary-adrenal axis of the rat.

This study has examined the effects of insulin-induced hypoglycemia on expression of the CRH, arginine vasopressin, and POMC genes and corresponding peptides in freely moving, unanesthetized, male Sprague-Dawley rats. Animals were infused with 150 mM NaCl for 3 days before the experimental day and were then administered insulin (4 U/kg) or saline iv. In one experiment animals were killed 0, 30, 60, or 90 min after insulin or saline, and RNA was isolated from anterior pituitary, cerebral cortex, and punches of the hypothalamic paraventricular and supraoptic nuclei. In a second experiment, animals were killed 90 min after insulin or saline treatment, and RNA was isolated from whole hypothalami. RNA was analyzed by Northern blot. Plasma glucose fell from 106 +/- 5 to 38 +/- 2 mg/dl after insulin administration and remained low for the duration of the experiment. Plasma levels of ACTH, corticosterone, and vasopressin were 10-, 6-, and 4-fold higher, respectively, in the insulin-treated vs. control animals (by analysis of variance, P less than 0.0001 in all cases), while plasma CRH was unchanged. During hypoglycemia POMC mRNA levels were 1.8-fold higher in the insulin-treated group (by analysis of variance, P less than 0.025). In contrast, paraventricular nucleus, whole hypothalamic, and parietal cortex CRH mRNA and vasopressin mRNA were unchanged. These data support previous studies which indicated that POMC gene expression is increased by hypoglycemia. However, we found no evidence for an increase in paraventricular nucleus or cerebral cortex CRH mRNA expression during hypoglycemia-associated stimulation of the hypothalamic-pituitary-adrenal axis, suggesting that another factor(s) may mediate the observed increase in POMC gene expression.

Adrenocorticotropic Hormone↗
PubMed1992

Medullary thyroid carcinoma: Australian experience with genetic testing.

Linkage analysis has been performed in four pedigrees with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (MTC) using pericentromeric chromosome 10 probes. Important information regarding carrier status has been provided in 10 individuals, many of whom would not have been identified by pentagastrin stimulation testing. We have also used pulsed field gel electrophoresis (PFGE) to link the probes H4.IRBP and pMCK2 to a 150 kb fragment. Using PFGE, no evidence was found in DNA from lymphocytes of a major DNA rearrangement in two individuals affected with MEN 2A and an individual with MEN 2B compared with normals. Metastatic MTC from one patient has been used to generate a cDNA library which will be used to screen for candidate MEN 2A and MEN 2B gene(s).

Carcinoma↗
PubMed1991

Detection of anti-ovarian antibodies by indirect immunofluorescence in patients with premature ovarian failure.

The sera of 30 patients with premature ovarian failure (POF) and a control group of 19 menopausal women were screened for anti-ovarian and other tissue antibodies. Anti-ovarian antibodies were detected by indirect immunofluorescence using monkey ovary substrates from two different commercial sources. Serum anti-ovarian antibodies were detected in only one of the patients with POF. This test does not appear to be reliable for the detection of serum anti-ovarian antibodies, and the clinical usefulness of screening patients with POF for anti-ovarian antibodies is questionable.

Adrenal Glands↗
PubMed1991

Renin gene expression in various tissues determined by single-step polymerase chain reaction.

1. Renin mRNA is present in the kidney and, in lower concentrations, in many extrarenal tissues and serves as an index of renin gene activity, as well as potential renin or prorenin synthesis in cell populations within those tissues. Unfortunately the quantity can be very low. 2. A new, highly sensitive technique is described for detection of renin mRNA that involves the enzyme Taq polymerase for both reverse transcription of renin mRNA into renin cDNA and for amplification of the 769-1099 nucleotide segment by the polymerase chain reaction (PCR), all of which involves a single reaction mixture. 3. In this way renin mRNA was detected in kidney and several extrarenal tissues as a PCR product of approximately 330 base pairs on agarose gels by ethidium-bromide staining or hybridization probing. The region of renin mRNA chosen for amplification spanned several intron sites in the coding sequence so that the presence of amplicants derived from genomic DNA could be readily discriminated, as a band of approximately 1.5 kilobases. 4. Thus single-step PCR offers a powerful new approach to detection of renin mRNA.

Animals↗
PubMed1990

Are the catabolic effects of tumor necrosis factor mediated by glucocorticoids?

The effect of tumor necrosis factor (TNF) on the hypothalamic-adrenal stress response was determined by infusion of TNF, 0, 2 x 10(5), and 4 x 10(5) U/kg per 24 hours, in parenterally fed male Wistar rats. Following infusions over 1 to 6 days, adrenal weight was increased with increasing dosage of TNF. Tumor necrosis factor at a dosage of 4 x 10(5) U/kg per 24 hours increased the plasma corticotropin level over the same period. In a further series of experiments the metabolic effects of TNF were compared with the effects of corticosterone, the predominant glucocorticoid in the rat. In comparison with controls, rats given corticosterone (75 mg subcutaneously) or TNF (2 x 10(5) U/kg per 24 hours) demonstrated decreased nitrogen balance and diminished carcass nitrogen content over a 6-day period. Tumor necrosis factor alone, however, induced a significant increase in liver nitrogen content and diminished jejunal mucosa DNA and protein levels in comparison with the control and corticosterone groups. Finally, adrenalectomized animals receiving basal corticosterone replacement were infused with TNF. Urinary nitrogen loss was significantly diminished in these animals compared with sham adrenalectomized controls, indicating that an intact adrenal stress response is necessary for the increased nitrogen loss following TNF infusion. Tumor necrosis factor may exert an important regulatory influence on the interorgan substrate flux that occurs during critical illness. The effects of TNF on skeletal muscle proteolysis can be simulated by adrenal glucocorticoid administration. The effects of this cytokine on visceral organs appear to be unique to TNF and cannot be reproduced by the administration of glucocorticoids alone.

Adrenal Glands↗
PubMed1990

The effect of exercise on circulating immunoreactive calcitonin in men.

Moderate-duration exercise increases serum catecholamine and serum calcium levels and might as a result be also expected to increase the levels of circulating serum immunoreactive human calcitonin (HCT). To explore this possibility, HCT was studied during and after moderate duration symptom-limited dynamic exercise in 13 healthy males, mean age 28 +/- 6.9 (SD) years. The mean duration of exercise using the Bruce treadmill protocol was 14.1 +/- 2.2 (SD) minutes. The mean heart rate (HR) peaked at 185 +/- 6 (SD) bpm which was 96.1% of the predicted maximal HR for age. Values for HCT, uncorrected for changes in plasma volume, showed a minimal decrease in the recovery phase, whilst HCT corrected for changes in plasma volume did not alter during exercise or recovery. The serum parathyroid hormone (PTH) also did not change. At peak exercise, uncorrected but not corrected values for plasma noradrenaline, adrenaline and dopamine had increased significantly. Corrected plasma total calcium increased during recovery. In summary, dynamic weight-bearing moderate-duration exercise did not elevate HCT in healthy males.

Adult↗
PubMed1990

Differential regulation of corticotropin-releasing hormone mRNA in rat brain.

Corticotropin-releasing hormone (CRH), a major hypothalamic component of the hypothalamic-pituitary-adrenal axis, has been localized to both the paraventricular nucleus (PVN) and cerebral cortex. Adrenalectomy causes an increase in PVN CRH content, whereas its effect on cortical CRH content is not clear. In the present study, adrenalectomy resulted in a threefold rise in the CRH mRNA content of anatomic micropunches of the PVN of individual rats (P less than 0.001), which was abolished by dexamethasone replacement. In parietal cortex, adrenalectomy did not affect CRH mRNA content, whereas hypophysectomy resulted in a twofold rise in CRH mRNA content (P less than 0.02), which was not significantly reduced by dexamethasone replacement. These results demonstrate that the CRH gene is negatively regulated by glucocorticoid in the PVN but not in cerebral cortex and that the increase in cortical CRH mRNA content after hypophysectomy may be evidence for negative regulation of cortical CRH gene expression by a second pituitary-dependent factor other than glucocorticoid.

Adrenalectomy↗
PubMed1989

Species-specific placental corticotropin releasing hormone messenger RNA and peptide expression.

The human placenta is a major site of synthesis of the hypothalamic neuropeptide corticotropin releasing hormone (CRH). We have examined placentae of several other species for expression of the CRH gene in this tissue. CRH mRNA was detected in human, gorilla, and rhesus monkey placentae, but not in rat, guinea pig and lemur placentae. A nonhuman primate may therefore be a suitable experimental model for studying placental CRH gene expression in vivo.

Animals↗
PubMed1989

Preprocorticotropin releasing hormone: cDNA sequence and in vitro processing.

Human corticotropin releasing hormone (hCRH) is expressed in both hypothalamus and placenta. Its expression in placenta increases markedly in the latter part of gestation. We have isolated and characterized a human placental CRH cDNA clone and performed in vitro translation of sense-strand hCRH cRNA synthesized from this cDNA and co-translational processing of the resulting preproCRH peptide. Sequence analysis of the cDNA confirms the exon-intron junctions predicted from the gene sequence and establishes the presence of at least two sites of transcription initiation of the human CRH gene in placenta. The translated preproCRH gene product contains a hydrophobic, functional signal sequence which suggests that placental CRH peptide is capable of being secreted. These structural features of the preproCRH mRNA and peptide may help to understand the regulation of placental CRH observed during human gestation.

Base Sequence↗
PubMed1989

Prevalence and characteristics of at-risk drinkers among a health visitor's caseload.

There has been a steady rise in alcohol consumption in the UK over the past 40 years. There is now plenty of evidence that this increase has been greatest in women and young people. Among young women excessive drinking leads to a variety of physical, mental and social problems of direct relevance to a health visitor who is concerned with the health and well being of her clients and their children. However the assessment of alcohol consumption is often not recognised as a part of the health visitors' role and no study was found which looked at the levels of alcohol consumption among a health visitors caseload. The aims of this study were to determine the amount of alcohol consumption in this group of people and to look at factors associated with heavy alcohol use.

Adolescent↗
PubMed1988

Vasopressin mRNA in the suprachiasmatic nuclei: daily regulation of polyadenylate tail length.

Daily variation has been found in the length of the polyadenylate tail attached to vasopressin messenger RNA in the suprachiasmatic nuclei, which is the location of an endogenous circadian pacemaker in mammals. No such variation was found in the supraoptic or paraventricular nuclei. This variation in the length of the polyadenylate tail may underlie the circadian rhythm of vasopressin peptide levels in cerebrospinal fluid and is a unique example of a daily rhythm in messenger RNA structure.

Animals↗
PubMed1988

Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta.

Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. We report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery.

Cells, Cultured↗