Adrenocorticotropin responses to endogenous and exogenous secretagogues in the sheep: specificity of glucocorticoid action.

Glucocorticoids act upon the hypothalamus and pituitary to regulate both corticotropin-releasing factors and adrenocorticotropin (ACTH) in a classical negative feedback loop. There are two distinct receptor systems in the central nervous system for glucocorticoids: type I corticosterone/cortisol-preferring, predominantly hippocampal receptors, and type II dexamethasone-binding receptors with a much broader distribution. To determine the relative roles played by these two receptors in determining basal and stress-induced ACTH/cortisol levels in the sheep, we have conducted two series of experiments.

Cloning and characterization of the growth hormone-dependent insulin-like growth factor binding protein (IGFBP-3) in the rat.

We report for the first time the complete amino acid sequence for the growth hormone dependent insulin-like growth factor binding protein (IGFBP-3) in the rat. A human IGFBP-3 clone was generated using the polymerase chain reaction (PCR) and used to screen a rat liver cDNA library. cDNA clones of the rat IGFBP-3 were isolated and the full amino acid sequence deduced.

Cloning and characterization of the rat alpha-inhibin gene.

The gene for the rat glycoprotein hormone alpha-inhibin has been cloned and characterized. The entire gene was found to be contained within a 5.5 kilobase EcoRI fragment.

Induction of ventricular morphogenesis and atrial natriuretic factor synthesis by thyroid hormone.

Thyroid hormones have been shown to increase atrial natriuretic peptide (ANP) synthesis in atria both in vitro and in vivo. In this study the effects of triiodothyronine (T3) administration on primary cultures of 6-day-old atrial and ventricular myocytes were studied. Levels of immunoreactive (ir-) ANP were determined by radioimmunoassay over 9 days of culture in cells cultured in the presence and absence of 10(-8) M T3.

Tissue-specific developmental expression of the kallikrein gene family in the rat.

Using a series of gene-specific oligonucleotide probes, we have explored the developmental pattern of expression of six members of the rat kallikrein gene family (PS, S1, S2, S3, K1, and P1) in the submandibular gland (SMG) and kidney of both sexes, the prostate and testis of the male, and the anterior pituitary gland (AP) of the female rat. PS (true kallikrein) mRNA was detected in early neonatal life in the SMG and kidney of both sexes. K1, a second kallikrein gene family member expressed in the adult kidney, had a developmental pattern similar to PS in the kidney.

Target tissue specificity of mineralocorticoids.

Mineralocorticoid receptors have equivalent, high affinity for aldosterone and for the physiological glucocorticoids cortisol and corticosterone, which circulate at much higher concentrations. In physiologic mineralocorticoid target tissues, glucocorticoids are excluded from mineralocorticoid receptors by conversion to their receptor-inactive 11-keto metabolites, by the enzyme 11beta hydroxysteroid dehydrogenase. Aldosterone, in contrast, escapes metabolism by cyclizing its 11-OH group with the reactive -CHO at position 18.

Helicobacter pylori: fact or fiction?

The recent isolation and classification of the spiral gastric bacteria Helicobacter pylori has led to an explosion of worldwide research. The data strongly suggest that H. pylori is the causative agent for type-B active chronic gastritis.

Oestrogen administration and the expression of the kallikrein gene family in the rat submandibular gland.

Using a series of oligonucleotide probes (18-21 mers) specific for members of the rat kallikrein/tonin (arginyl-esteropeptidase) gene family (PS, S1, S2, S3, K1, P1), we have shown by Northern blot analysis that all six genes are expressed in the submandibular gland (SMG), with PS (true kallikrein) the most abundant in both male and female rats. Though female levels of PS mRNA are similar to that in the male, levels of mRNA from both the kallikrein-like (S1, K1, P1) and tonin (S2)/tonin-like (S3) genes are all substantially lower in the female than in the male rat. In contrast with the oestrogen dependence of anterior pituitary kallikrein (PS) gene expression, oestrogen administration (6 micrograms/day for 8 days) to castrate male or female rats is without effect on PS or S1, S2, S3, K1, P1 mRNA levels in the SMG.

Inhibin concentrations in ovarian and jugular venous plasma and the relationship of inhibin with follicle-stimulating hormone and luteinizing hormone during the ovine estrous cycle.

A heterologous RIA for ovine inhibin was developed which was sufficiently sensitive and specific to describe the peripheral concentrations of immunoreactive inhibin (iINH) during the estrous cycle of the ewe and to examine the effects of cautery of ovarian follicles on concentrations of iINH in ovarian and jugular venous plasma. Parallel logit-log dose-response lines were observed among ovine follicular fluid, ewe plasma, and pure native ovine (31 kDa) and bovine (31 kDa) inhibin. iINH could not be detected in ovariectomized ewe plasma, and there was no apparent cross-reactivity with a variety of structurally related and unrelated hormones and peptides, except a monomeric form of the alpha-subunit of INH, iINH in follicular fluid was 10(4)-fold higher than that in ovarian venous plasma, which was 3-fold higher than that in peripheral plasma.

Food variety is associated with less macrovascular disease in those with type II diabetes and their healthy controls.

In developed countries, the health outcome most under scrutiny with respect to food intake is macrovascular disease. Since food is so complex, global indices of food intake are required to assess the relation. In the present study, an index of food variety was examined for its ability to predict changes in the arterial wall.

The scleroderma neck sign.

The scleroderma neck sign, as described by Barnett, is a visible and palpable tight band over platysma in the hyperextended neck. A recent survey of 76 patients with scleroderma revealed that more than 90% had the scleroderma neck sign. Our study was performed using 15 patients with scleroderma and 30 controls including 3 with primary Raynaud's disease to examine the specificity of the scleroderma neck sign, and to look for a correlation between the presence of the scleroderma neck sign and histological changes of scleroderma in the skin overlying platysma.

Relative contributions of chemo-attractant and terminal components of complement to anti-glomerular basement membrane (GBM) glomerulonephritis.

The relative contributions of chemo-attractant and terminal components of complement to heterologous phase glomerular injury was studied in anti-GBM glomerulonephritis in rabbits. Normal rabbits (complement intact) were given anti-GBM antibody at a dose which resulted in 140 micrograms specific kidney-fixed antibody per gram of renal cortex, and developed significant proteinuria (1910 +/- 327 mg/24 h; control 18.2 +/- 6.

Direct pituitary inhibition of prolactin secretion by dopamine and noradrenaline in sheep.

The effects of dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) on the release of prolactin were examined in ovariectomized ewes. Infusion of dopamine (0.5 or 1 microgram/kg per min for 2 h i.

Retinoic acid affects the cell cycle and increases total protein content in epithelial cells.

Retinoids and particularly retinoic acid (RA) have been incriminated in the adaptation to uninephrectomy and compensatory kidney growth in humans. However, there is no data assessing the effects of RA on renal cells. Since the bulk of the compensatory kidney growth is due to tubular cells, we studied the effects of RA, retinol and epidermal growth factor (EGF) on a rabbit kidney epithelial cell line RK13 in culture.

Intrapituitary cell-cell communication regulates ACTH secretion.

Exposure of rat anterior pituitary cells in culture to a cytotoxin specific for CRF-target cells is followed by increased basal ACTH secretion from the remaining cells three days after the last exposure to the cytotoxin. When CRF-target-depleted populations are co-cultured with unexposed pituitary cells ACTH secretion is more than double that predicted in the absence of cell-to-cell interaction. These data provide evidence for an intrapituitary cell-to-cell signalling system modulating ACTH secretion.

The effects of deoxyspergualin on lymphocytes and monocytes in vivo and in vitro.

It has been suggested that deoxyspergualin, a new immunosuppressant, may be immunosuppressive via a purely antimonocyte action. As this appears to be unlikely, this study examines the effect of deoxyspergualin on lymphocyte and monocyte function in vivo and in vitro. It is demonstrated that deoxyspergualin inhibits human lymphocyte proliferation in response to mitogens and allogeneic stimulation.

Immunocytochemical demonstration of mineralocorticoid receptors in rat and human kidney.

Using a polyclonal antiserum against the hinge region of the recently cloned human mineralocorticoid receptor (MR) and indirect peroxidase immunohistochemistry, we have shown MR-like immunoreactivity (LI) in superficial nephron segments, including distal convoluted tubule, connecting piece and initial cortical collecting duct. The absence of staining in cells tentatively identified as intercalated cells on light microscopy was confirmed by pre-embedding electron microscopy. Though the intracellular distribution of immunostaining varied with the fixative used, the cellular distribution of MR-LI is in good general agreement with earlier micropuncture and autoradiographic studies.

Kallikrein-gene expression in the rat gastrointestinal tract.

The serine proteinase glandular kallikrein has been demonstrated in the gastrointestinal tract, although there is some doubt as to whether it is synthesized there or derives from exocrine-gland secretions. Using a rat pancreatic kallikrein cRNA probe we have demonstrated kallikrein-like gene expression in the corpus, duodenum, jejunum, ileum, caecum and colon, and compared the pattern of expression with that of the gastrointestinal peptides somatostatin, gastrin and glucagon. In addition, using a panel of oligonucleotide probes specific for various members of the rat kallikrein-gene family, we have shown that the kallikrein-like gene expressed appears to be expressed as true kallikrein.

Statistical measurements of accuracy in cervical cytology.

Statistical measures that can be used to monitor the level of accuracy of cervical cytologic screening are examined: sensitivity, the false-negative rate, the interval cancer rate among women with negative reports and the predictive value of a positive test. Sensitivity and the false-negative rate are subject to biases and problems of determination that may make them less useful as measures of accuracy. The interval cancer rate and the positive predictive value may be better methods of assessing the frequency of serious abnormalities following negative cytologic reports and the accuracy of cytologic reports of serious abnormalities, respectively.

Glucocorticoids regulate ovine hypophysial portal levels of corticotropin-releasing factor and arginine vasopressin in a stress-specific manner.

Hypophysial portal circulation levels of immunoreactive (ir) CRF, immunoreactive arginine vasopressin (ir-AVP), and systemic ir-ACTH and cortisol were determined in dexamethasone-infused (20 micrograms/h) ewes, both under basal conditions and in response to audiovisual and hypoglycemic stress. Glucocorticoid infusion lowered mean basal levels of ir-CRF (P less than 0.05), ir-ACTH (P less than 0.