Search PubMed⌕ Search

Biomedical subjects

Z Ota

Publications and source records attributed to Z Ota.

At least 217 records · Page 12Linked to original sources

Cortisol responsiveness to insulin-induced hypoglycemia in Cushing's syndrome with huge nodular adrenocortical hyperplasia.

A 51-yr-old male patient with a 3 yr history of Cushing's syndrome is described. The baseline plasma cortisol level was elevated, while the plasma ACTH levels remained at an undetectable level. Dynamic testing of pituitary-adrenal function revealed no suppression after 8 mg of dexamethasone, and there was no response to metyrapone or CRF, while plasma cortisol showed a hyperresponse to synthetic ACTH. Plasma cortisol responded to insulin-induced hypoglycemia without an obvious ACTH response. These and the computerized tomography data suggested a "huge" bilateral nodular adrenocortical hyperplasia which was later confirmed by surgery. The left and right adrenal glands weighed 55 and 76 g, respectively. In vitro experiments, using the adrenal tissue, showed that there was an adrenal cortisol response to 1-39 ACTH but not to regular insulin, arginine vasopressin, angiotensin II, norepinephrine or epinephrine. These results indicate that plasma cortisol responded to a slight hypoglycemia-induced plasma ACTH change which was not detected in the ACTH radioimmunoassay or to factors other than ACTH which might be induced by hypoglycemia.

Adrenal Cortex↗

Effect of synthetic atrial natriuretic polypeptide on hemorrhage-induced adrenocorticotropin secretion of the rat.

The effect of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) on the in vivo and in vitro release of ACTH and corticosterone was examined. In the in vivo study ACTH and corticosterone responses to rapid 2-ml/rat hemorrhage were measured in sixteen conscious rats after alpha-hANP administration. The hemorrhage increased plasma ACTH and corticosterone concentrations in the control group of rats (p greater than 0.01). ANP inhibited hemorrhage-induced ACTH secretion (p less than 0.05), but the plasma corticosterone response was not affected. In the in vitro study a high concentration of ANP (1 microM) reduced basal corticosterone secretion from the isolated rat adrenal gland (p less than 0.05), but the response to ACTH (10 ng/ml) and dibutyryl cyclic AMP (0.5 mM, 5.0 mM) was not affected. Our data suggest that ANP inhibits hemorrhage-induced ACTH secretion from the anterior pituitary but inhibits corticosterone secretion from the adrenal gland very weakly.

Adrenal Glands↗

Effects of (D-ala2, met5)-enkephalinamide and naloxone on ACTH and corticosterone secretion.

An intravenous administration of (D-ala2, met5)-enkephalinamide (DALA) caused a significant elevation of plasma ACTH and corticosterone at 10 to 20 min after injection in unanesthetized freely moving rats. An intraperitoneal administration of cyproheptadine tended to reduce plasma ACTH and corticosterone levels at 60 min after injection, but it did not attenuate the DALA-induced ACTH and corticosterone elevation. A large dose of naloxone (1-10 mg/kg body weight) caused a significant elevation in plasma corticosterone, but naloxone at 10 mg/kg body weight reduced the basal ACTH level and DALA-induced ACTH elevation. When both DALA and naloxone were injected, the steroidogenic effect was attenuated. Neither DALA nor naloxone affected the basal ACTH release and CRF-induced ACTH stimulation in rat anterior pituitary cell cultures. These results suggest that DALA acts at the extra-hypophyseal level to stimulate ACTH and corticosterone and that the naloxone stimulatory effect on steroidogenesis acts on the adrenal gland or is mediated by stimulating corticosterone stimulating factors other than ACTH.

Adrenocorticotropic Hormone↗

Corticotropin-releasing factor (CRF) and vasopressin concentration in major brain regions after adrenalectomy and their involvement in adrenalectomy-induced ACTH elevation.

CRF and vasopressin concentrations in major brain regions after bilateral adrenalectomy and their involvement in adrenalectomy-induced ACTH secretion were investigated. At 5, 14 and 28 days after bilateral adrenalectomy, the plasma ACTH level was greatly elevated, whereas hypothalamic CRF content was reduced at 5 days and was not changed at 14 and 28 days after adrenalectomy. The CRF concentration in the medulla oblongata was reduced at 2-4 weeks after adrenalectomy. On the other hand, the arginine vasopressin (AVP) concentration was significantly elevated 2-4 weeks after adrenalectomy. An intrajugular administration of anti-ovine or anti-rat CRF serum significantly suppressed the elevated plasma ACTH level in adrenalectomized, freely moving rats, whereas anti-AVP serum or antipressor AVP antagonist, dpTyr(Me)AVP did not suppress the ACTH level. These results indicate that CRF played an important role in the adrenalectomy-induced ACTH elevation but that vasopressin was not involved.

Adrenalectomy↗

Multiple endocrine neoplasia with Cushing's syndrome due to paraganglioma producing corticotropin-releasing factor and adrenocorticotropin.

A male patient with corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH)-producing syndrome is described. Soon after being referred to us the patient developed pneumonia, anaemia, oedema and respiratory distress, and died on the 24th day after admission. Autopsy and histology revealed that he had a rare type of multiple endocrine neoplasia (type 1 + paraganglioma) with a mediastinal paraganglioma, parathyroidal hyperplasia, pancreatic islet cell adenoma, duodenal multiple carcinoid tumours and adrenocortical nodular hyperplasia. It was not possible to examine the pituitary. The paraganglioma contained a large amount of immunoreactive (IR)-CRF (606 ng/g wet weight), IR-ACTH (59.4 ng/g wet weight), IR-human proopiomelanocortin n-terminal (1-76) peptide (hNT, 156.8 ng/g wet weight) and IR-beta-lipotropin (beta-LPH, 146.9 ng/g wet weight). The major IR-ACTH, beta-LPH and IR-hNT were eluted at ACTH-(1-39), beta-LPH and hNT marker positions, respectively. Big ACTH was not detected. IR-CRF eluted at the human CRF marker position on Sephadex G-75 chromatography and high performance liquid chromatography (HPLC). The IR-CRF fraction from the HPLC showed CRF bioactivity which paralleled that of synthetic human CRF in monolayer cultured rat anterior pituitary cells. Our results suggest that not only ACTH but CRF produced by the paraganglioma was responsible for the patient's Cushing's syndrome.

Adrenocorticotropic Hormone↗

Mechanism of hematuria. I. Electron microscopic demonstration of the passage of a red blood cell through a glomerular capillary wall in rat masugi nephritis.

Masugi nephritis was induced in Sprague-Dawley rats by an intravenous injection of rabbit anti-rat kidney serum. In the autologous phase of the disease, three of 18 rats manifested continuous hematuria. Ultrastructural examination of renal glomeruli by transmission and scanning microscopy revealed gaps in the basement membranes, and the transcapillary passage of red blood cells through the discontinuous regions in the hematuric rats. Control animals revealed no gaps in the glomerular basement membranes regardless of the method used in their preparation for electron microscopy. These data support the hypothesis that hematuria is a result of the passage of red blood cells through gaps in the glomerular basement membrane in Masugi nephritis.

Animals↗

Effect of indapamide on atrial natriuretic polypeptide receptor in spontaneously hypertensive rat kidney.

The effect of a hypotensive state on atrial natriuretic polypeptide (ANP) receptors of the kidney treated by indapamide was investigated in spontaneously hypertensive rats (SHRs). SHRs aged 12 weeks were injected intraperitoneally with indapamide (10mg/kg/day) for 10 days and an ANP radiolabeled receptor assay (RRA) was done on the 11th day. The systolic blood pressure of SHRs injected with indapamide (IDP group) was statistically lower than that of SHRs injected with 2% gum Arabic solution (control group). Concerning the RRA of ANP in the SHR kidney, high affinity and low capacity binding sites were observed in the IDP group (Kd = 0.220 +/- 0.059 nM, Bmax = 6.10 +/- 2.36 fmol/100 micrograms) compared with the control group (Kd = 0.401 +/- 0.147 nM, Bmax = 9.96 +/- 2.50 fmol/100 micrograms). These finding suggested that the hypotensive state induced by treatment with indapamide may change the ANP receptor in kidneys of a SHR.

Animals↗

Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats.

The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neuro-intermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR.

Animals↗

Characterization of the spontaneous DNA-synthesizing and/or IgG-secreting cells in peripheral blood from patients with systemic lupus erythematosus.

Characterization of the cells responsible for spontaneous DNA synthesis and/or IgG secretion in systemic lupus erythematosus (SLE) was undertaken by fractionation of the peripheral blood mononuclear cells (PBM). Each fraction was analyzed for its capacity to incorporate [3H]thymidine [( 3H]TdR) and secrete IgG without mitogen. The non-E rosette-forming cell (non-ERRC) fraction, which consisted of the surface immunoglobulin-positive [sIg(+)] cells and null cells, revealed a markedly increased spontaneous DNA synthesis (620.0 +/- 586.9 cpm) during the first hour of culture and an elevated spontaneous IgG secretion (8639 +/- 2630 ng/ml) during 9 days of culture. Of particular interest was the finding that both increased responses were conducted by the null cells; the null cell population had approximately a fourfold relative increase of [3H]TdR incorporation and a 60-fold relative increase of IgG secretion compared with the sIg(+) cell population. These results suggest that SLE patients have a small population of preactivated B-cell lineage cells, which lack sIg or have a very low density of sIg.

Antibody Formation↗

Purification of insulin-binding antibody by affinity chromatography using monocomponent insulin as ligand.

Insulin-binding antibody (IBA) was purified by affinity chromatography using porcine monocomponent (MC) insulin as the ligand. The purity of the antibody was compared with that of the antibody extracted using porcine crystalline (Cr) insulin. Comparing the antibody solutions obtained with MC insulin (MC-lig-sol) or Cr insulin (Cr-lig-sol), the content of IBA in Cr-lig-sol was higher than in MC-lig-sol, but the content of proinsulin-binding antibody (PBA) in MC-lig-sol was very small and statistically lower than that in Cr-lig-sol (P less than 0.01). Adding native MC insulin to a competitive radioimmunoassay suppressed the IBA titer obtained with MC insulin more than that obtained with Cr insulin. By adding native proinsulin in a similar assay system, the PBA titer obtained with Cr insulin was suppressed more than that extracted with MC insulin. Scatchard analysis of the 2 solutions showed that the affinity constants of high affinity antibodies were almost identical, but that of low affinity antibody in MC-lig-sol was larger than in Cr-lig-sol. The binding capacity of low affinity antibody in Cr-lig-sol was 15 times as much as that in MC-lig-sol. Using MC insulin, instead of Cr insulin, as the ligand in affinity chromatography increased the purity of recovered IBA. chromatography increased the purity of recovered IBA.

Chromatography, Affinity↗

Calmodulin inhibitors decrease the CRF-and AVP-induced ACTH release in vitro: interaction of calcium-calmodulin and the cyclic AMP system.

The effect of N-(6-aminohexyl)-5-chloro-naphthalene-1-sulfomide (W-7) and trifluoperazine (TFP) was examined on ACTH release from cultured rat anterior pituitary cells and pituitary halves. These drugs significantly inhibited the ACTH release induced by synthetic ovine corticotropin-releasing factor (CRF) in a dose-related manner. In pituitary halves, arginine vasopressin (AVP) at 10 and 100 ng/ml showed almost the same ACTH-releasing activity as CRF at the same concentrations. W-7 and TFP inhibited the CRF-and AVP-induced ACTH release from pituitary halves. The cyclic AMP levels in the pituitary halves were significantly increased by CRF, but not AVP. Although W-7 inhibited CRF-induced ACTH release, it did not have an effect in cyclic AMP accumulation. These results suggest that CRF exerts ACTH-releasing activity through both the calcium-calmodulin system and cyclic AMP system and that AVP stimulates ACTH release mainly through the calcium-calmodulin system.

Adrenocorticotropic Hormone↗

Brain corticotropin-releasing factor (CRF) and catecholamine responses in acutely stressed rats.

Ether-laparotomy stress produced a rapid increase in rat hypothalamic CRF concentration, followed by a rapid reduction and subsequent increase. Cold-restraint stress significantly reduced hypothalamic CRF concentration at 15 min after stress onset. Serum ACTH and corticosterone levels were significantly elevated at 15 min after the onset of both stresses. The CRF responses in the medulla oblongata were not similar to the hypothalamic CRF responses. Norepinephrine concentration in the hypothalamus was reduced, whereas dopamine concentration in the hypothalamus and medulla oblongata was significantly increased. Epinephrine concentrations in these tissues did not show any significant change throughout the stress period. The observations lead to the following conclusions: hypothalamic CRF plays a major role in stimulating ACTH secretion under acute stress; the reduction in hypothalamic CRF is due to an excess release in the early phase of acute stress; hypothalamic CRF and medulla oblongata CRF are controlled by different mechanisms; norepinephrine in the hypothalamus may not be involved in stimulating hypothalamic CRF secretion in the early phase of acute stress; and catecholamines are regulated differently in the hypothalamus and medulla oblongata.

Adrenocorticotropic Hormone↗