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Biomedical subjects

Y Nakagami

Publications and source records attributed to Y Nakagami.

At least 37 records · Page 2Linked to original sources
PubMed1989

Responses to corticotropin-releasing hormone and its bound and free forms in pregnant and nonpregnant women.

Plasma CRH levels are considerably higher in women during the third trimester of pregnancy than in non-pregnant women. Most of plasma CRH in pregnant women is bound to CRH-binding protein (CRH-BP). To gain further insight into CRH physiology during pregnancy, we measured the responses of plasma ACTH and cortisol and the changes in bound and free forms of CRH in plasma after human CRH administration (2 micrograms/kg) in five pregnant (39-40 weeks of pregnancy) and five nonpregnant women. The mean basal plasma ACTH and cortisol levels in the pregnant women were higher than those in the nonpregnant women. However, the maximum increments in plasma ACTH and cortisol levels and the integrated ACTH and cortisol responses, after subtraction of the basal levels after CRH administration, were similar in the two groups. The plasma CRH half-time in the pregnant group was similar to that in the nonpregnant group. The mean basal plasma CRH level in the nonpregnant women was 1.5 +/- 0.2 (+/- SE) pmol/L, and that in the pregnant women was 360 +/- 35 pmol/L. On gel filtration chromatography, almost all of the CRH in the plasma was protein bound (320 +/- 30 pmol/L) in the pregnant women; no CRH peaks were detected in nonpregnant women because of the low plasma CRH levels. After CRH administration, the level of the bound form of plasma CRH was highest at 5 min, and then declined to a plateau at 15 min and 30 min in the pregnant women. In the nonpregnant women, protein-bound CRH also was highest at 5 min, but it progressively declined thereafter. The disappearance rate of the bound CRH in plasma from the nonpregnant women was similar to that of the second compartment of the plasma decay curves of the free CRH from both groups. We conclude that the plasma ACTH and cortisol responses to exogenous CRH are similar in pregnant and nonpregnant women, the effect of CRH-BP on the disappearance of plasma CRH is minimal, and plasma CRH-BP in pregnant women has the capacity to bind additional CRH.

Adrenocorticotropic Hormone↗
PubMed1988

In vitro study on proopiomelanocortin messenger RNA levels in cultured rat anterior pituitary cells.

The fundamental examination on the measurement of proopiomelanocortin (POMC) mRNA levels in cultured rat anterior pituitary (AP) cells was studied. In addition, the detailed study on time- and dose-related effects of corticotropin-releasing factor (CRF) and dexamethasone on the level of POMC mRNA in AP cells in vitro was examined. Basal levels of POMC mRNA in AP cells cultured with serum initially declined after 1-day culture, gradually increased and reached a peak after 3-day culture, and then slightly decreased after 4- and 5-day culture. These mRNA levels after 3-day culture did not change through subsequent 15-hr incubation without serum. CRF treatment caused a time- and dose-dependent increase in POMC mRNA levels. The minimum effective dose of CRF was 0.1 nM for 15-hr incubation. The significant increase in POMC mRNA levels was observed after 3 hrs of 1 nM CRF treatment with a 2-fold elevation seen after 15 hrs of exposure. Dexamethasone treatment caused a dose-dependent decrease in POMC mRNA levels in AP cells. The minimum effective dose was 0.1 microgram/ml and such mRNA levels did not decrease until 15 hrs of exposure.

Animals↗
PubMed1988

A compound adrenal medullary tumor (pheochromocytoma and ganglioneuroma) and a cortical adenoma in the ipsilateral adrenal gland. A case report with enzyme histochemical and immunohistochemical studies.

Neoplasms of all the adrenal parenchymatous elements [i.e., a compound adrenal medullary tumor (MT) consisting of pheochromocytoma (Pheo) and ganglioneuroma (GN) and a cortical adenoma] were found in the right adrenal gland of a 53-year-old man. A mature GN element was predominant in the MT, and nodules of small polygonal Pheo cells were scattered in GN. No neuroblastomatous element or malignant Pheo was found. The cortical adenoma consisted of compact cells and clear cells; it showed 3 beta hydroxysteroid dehydrogenase, glucose-6-phosphate dehydrogenase, and succinate dehydrogenase activity. The nonneoplastic cortex was slightly atrophic and showed weaker activity of the enzymes, suggesting that the adenoma was cortisol-producing. The cortex surrounding the MT was invaded and replaced by either GN or Pheo. In some places, however, hypertrophic compact cells constituted the cortex and were in contact with ACTH-immunoreactive chromaffin cells. A few of the latter were also positive for other proopiomelanocortin (POMC)-derived peptides. Pheo cells in the other parts were negative for POMC-derived peptides.

Adenoma↗
PubMed1988

Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro.

The effects of corticotropin-releasing hormone (CRH) and dexamethasone on proopiomelanocortin (POMC) mRNA levels in cultured pituitary adenoma cells were studied in 10 patients with Cushing's disease. As a control, POMC mRNA levels in cells from nonadenomatous tissues were examined in four patients. Human POMC mRNA in the cells was analyzed by Northern blot hybridization. Human POMC DNA probe hybridized with only a single size class of RNA (approximately 1,200 nucleotides) from the adenoma and nonadenoma cells of each patient. The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone. CRH increased POMC mRNA levels in these cells in a dose- and time-dependent manner. The minimum concentration of CRH required to elevate POMC mRNA levels in these cells exposed for 15 h was 0.1 nM. The minimum duration of 1 nM CRH treatment required to increase these levels was 3 h under our conditions. Inhibitory effects of 1 and 10 micrograms/dl dexamethasone on ACTH release and POMC mRNA levels in nonadenoma cells were greater than those in adenoma cells. These results suggest the following: (a) that the mRNA in cultured pituitary adenoma cells is qualitatively the same as that in vivo; (b) that responses of mRNA levels to CRH are time- and dose-dependent; and (c) that adenoma cells resist the inhibitory effect of dexamethasone on POMC mRNA levels and ACTH release.

Adenoma↗
PubMed1988

Insulin-induced hypoglycemia increases proopiomelanocortin messenger ribonucleic acid levels in rat anterior pituitary gland.

To study the effect of acute stress on ACTH secretion and synthesis in rat pituitary and hypothalamus, ACTH content and POMC mRNA levels (measured by use of Northern blot analysis) in these tissues as well as the levels of ACTH in plasma and those of CRF in the hypothalamus were determined after insulin-induced hypoglycemia. Plasma ACTH levels increased at 30 and 60 min. ACTH levels in the anterior pituitary lobe (AP) decreased at 30 min, and then returned to control levels at 60 min. No change was seen in the intermediate-posterior pituitary (IP) or the hypothalamus after insulin injection. CRF levels decreased at 30 and 60 min, then returned to control levels at 90 min in the medial basal hypothalamus, including the median eminence. Hybridization with a cDNA probe revealed a single size class of POMC mRNA in AP, IP, and hypothalamus, and the size of POMC mRNA in these tissues did not change during the experimental period. POMC mRNA levels in AP increased at 60 min and reached a peak at 120 min, but those in IP and hypothalamus did not change. These results suggest that 1) insulin-induced hypoglycemia stimulates both secretion and synthesis of ACTH (at least by increasing POMC mRNA levels) in the AP, and 2) the levels of ACTH and POMC mRNA in the IP and hypothalamus are not affected by insulin-induced hypoglycemia.

Adrenocorticotropic Hormone↗
PubMed1988

Insulin-induced hypoglycemia increases corticotropin-releasing factor messenger ribonucleic acid levels in rat hypothalamus.

To study the effect of acute stress on CRF release and synthesis in rat hypothalamus, ACTH levels in plasma, CRF contents in the median eminence (ME), and CRF mRNA levels in the hypothalamus without ME and cerebral cortex were determined after insulin-induced hypoglycemia. Plasma ACTH levels increased at 30 and 60 min, while ME CRF content decreased at 30 and 60 min, then returned to the control level at 90 min. Hybridization with a cRNA probe revealed a single size class of CRF mRNA in the hypothalamus and cerebral cortex (approximately 1300 nucleotides), and the size of CRF mRNA in these tissues did not change during the experimental period. CRF mRNA levels in the hypothalamus increased to 130% of the control value at 30 min and reached a peak (186% of the control value) at 120 min, but these levels in the cerebral cortex did not change. These results suggest that insulin-induced hypoglycemia stimulates CRF synthesis by increasing CRF mRNA levels in the hypothalamus as well as CRF release, and that release and synthesis of CRF in the cerebral cortex are independent of those in the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1988

Characterization of corticotropin-releasing hormone binding protein in human plasma by chemical cross-linking and its binding during pregnancy.

A human plasma CRH-binding protein (CRH-BP) was identified and characterized by chemical cross-linking of 125I-Tyr-hCRH to human plasma using disuccinimidyl suberate. The apparent mol wt of the cross-linked complex determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography was approximately 43,000. The mol wt was slightly lower in the nonreduced state, suggesting the presence of intramolecular disulfide bonds. Subtracting the mol wt of 125I-Tyr-CRH, the BP appeared to have a mol wt of approximately 38,000. Binding was specific since the appearance of the 43,000 dalton band was not affected by unlabeled ACTH, vasopressin, serum albumin, or gamma-globulin, but was inhibited by unlabeled hCRH dose dependently. Pretreatment of plasma with 0.1 mol/L HCl, 0.01 mol/L NaOH, 10 mmol/L dithiothreitol, or trypsin before cross-linking abolished its ability to bind 125I-Tyr-hCRH. Rat, rabbit, or goat plasma or human cerebrospinal fluid did not bind 125I-Tyr-CRH. It is unlikely that CRH-BP is a CRH receptor, because the estimated mol wt of the CRH-BP is smaller than the reported size of CRH receptors, and the CRH-BP did not bind to ovine CRH. The binding of 125I-Tyr-CRH to CRH-BP decreased in the third trimester of pregnancy, when plasma CRH levels were markedly elevated. However, after dissociating endogenous CRH from the CRH-BP, the binding was almost the same as in nonpregnant subjects. In addition, CRH-BP inhibited CRH-induced ACTH secretion from cultured rat anterior pituitary cells. We conclude that most of the increased plasma CRH found in pregnant women is bound to CRH-BP, and so is inactive, therefore plasma ACTH levels do not increase to above the normal range.

Adrenocorticotropic Hormone↗
PubMed1987

Inhibitory effect of norepinephrine on immunoreactive corticotropin-releasing factor release from the rat hypothalamus in vitro.

Effects of catecholamines on immunoreactive corticotropin-releasing factor (I-CRF) release from the rat hypothalamus were examined using a rat hypothalamic perifusion system and a rat CRF RIA in vitro. Norepinephrine had a potent inhibitory effect on I-CRF release in a dose-dependent manner at 0.1 nM-1 microM concentrations, but dopamine did not. This inhibitory effect of norepinephrine was completely blocked by propranolol, but only partially blocked by phentolamine. Isoproterenol also had a potent inhibitory effect at 0.01-100 nM concentrations, and a high dose of phenylephrine (10 nM) inhibited I-CRF release. Clonidine did not influence I-CRF release. These results suggest that norepinephrine inhibits I-CRF release mainly through the beta-adrenergic receptor and partially through the alpha 1-receptor.

Adrenergic Agonists↗
PubMed1987

Time course study on the effect of reserpine on hypothalamic immunoreactive CRF levels in rats.

A time course study on the changes of rat hypothalamic corticotropin-releasing factor (CRF) levels and ACTH levels in plasma, pituitary and hypothalamus after an acute treatment with reserpine was examined using a rat CRF RIA. The massive and prolonged depletion of hypothalamic norepinephrine and dopamine levels provoked by a single injection of reserpine (2 and 8 mg/kg, i.p.) caused a transient decrease of hypothalamic CRF levels and ACTH levels in the anterior pituitary glands, and an increase in plasma ACTH levels. There was a strong correlation between the depletion of hypothalamic CRF and norepinephrine levels. These results suggest that: acute depletion of hypothalamic norepinephrine levels cause the initial release of CRF that stimulates pituitary ACTH secretion, and the depletion of CRF and ACTH stores at the early stage; and noradrenergic pathways may be involved in the inhibitory mechanism of CRF release.

Adrenocorticotropic Hormone↗
PubMed1987

Stimulatory effect of acetylcholine on immunoreactive corticotropin-releasing factor release from the rat hypothalamus in vitro.

Effects of acetylcholine (Ach) and gamma-aminobutyric acid (GABA) on immunoreactive corticotropin-releasing factor (CRF) release from the rat hypothalamus were examined using a rat hypothalamic perifusion system and a rat CRF RIA in vitro. Ach stimulated CRF release in a dose-dependent manner (1 pM-1 nM). One nM Ach-induced CRF release was inhibited by atropine in a dose-dependent manner (1-100 nM), but was inhibited by only a high concentration (100 nM) of hexamethonium. In addition, such Ach-induced CRF release was inhibited by norepinephrine. GABA did not influence basal CRF release. These results suggest that Ach stimulates CRF release mainly through muscarinic receptors at least under our conditions.

Acetylcholine↗
PubMed1987

Phase III trial of the Japanese Urological Cancer Research Group for Adriamycin: cyclophosphamide, adriamycin and cisplatinum versus cyclophosphamide, adriamycin and 5-fluorouracil in patients with advanced transitional cell carcinoma of the urinary bladder.

A non-randomized clinical study on systemic combination chemotherapy was conducted by the Japanese Urological Cancer Research Group for Adriamycin to compare the effectiveness of CAP (cyclophosphamide 200-500 mg/m2, adriamycin 30-50 mg/m2 and cisplatin 30-50 mg/m2) and CAF (cyclophosphamide 200-500 mg/m2, adriamycin 30-50 mg/m2 and 5-fluorouracil 250 mg/m2) in 123 patients (104 evaluable) with advanced and/or metastatic cancer of the urinary bladder. Among 96 patients who were non-randomly selected to receive CAP, 4 achieved complete remission, 12 achieved partial remission, 7 achieved minor response, 30 had stable disease, and 43 had disease progression. The response in the 8 patients who received CAF were: partial remission in 1 and progressive disease in 7. The overall response rate to CAP therapy was 17%, as against 13% for CAF therapy. The median duration of survival with CAP was 29 weeks and with CAF, 22 weeks. The differences between the two groups in duration of survival and response rate were not statistically significant. Complete and/or partial remissions were observed in the lymph nodes, lung and liver in 32%, 24%, and 57% of cases, respectively. There was no objective response in bone metastasis. The main side effects of CAP were anorexia (88%), nausea and/or vomiting (81%), alopecia (65%), leukopenia (72%), anemia (48%), and renal dysfunction (17%). No patients died as a result of toxicity of these combination chemotherapy modalities.

Adult↗
PubMed1987

Immunoreactive corticotropin-releasing factor in rat plasma.

Immunoreactive ACTH (I-ACTH) levels in the rat anterior pituitary and plasma, and immunoreactive corticotropin-releasing factor (I-CRF) concentrations in the median eminence (ME) and plasma were determined after adrenalectomy and in insulin-induced hypoglycemia. I-CRF was detected in plasma from normal rats (mean +/- SD, 5.6 +/- 0.9 pg/ml; n = 6). Gel filtration chromatography of I-CRF from pooled plasma of these rats revealed a single peak which eluted in the position of authentic rat CRF. I-CRF levels in ME and I-ACTH levels in anterior pituitary decreased immediately after adrenalectomy, then gradually increased to high levels 14 days after surgery. Plasma I-CRF and I-ACTH concentrations increased immediately after surgery, slightly decreased to near the control levels at 24 h, and then increased to high concentrations 14 days after surgery. Plasma and ME I-CRF levels 14 days after adrenalectomy, followed by daily dexamethasone replacement, were almost the same as control levels. In insulin-induced hypoglycemia, plasma I-ACTH and I-CRF concentrations increased and ME I-CRF content decreased at 30 and 60 min. These results suggest that plasma I-CRF levels reflect changes in hypothalamic CRF levels.

Adrenalectomy↗
PubMed1987

A short negative feedback mechanism regulating corticotropin-releasing hormone release.

The effect of ACTH administration on plasma CRH levels was studied. In five patients with Addison's disease and three patients with hypopituitarism, bolus iv injection of 0.25 and 0.5 mg ACTH-(1-24) reduced plasma CRH levels (that had become elevated 48 h after discontinuation of corticosteroid replacement) to near-normal levels at 30-60 min in a dose-dependent manner. Plasma immunoreactive beta-endorphin levels were similarly decreased in patients with Addison's disease. ACTH-(1-24) (0.25 and 0.5 mg) injection failed to inhibit plasma CRH levels in five normal subjects. Basal CRH release from the rat hypothalamic median eminence in vitro was inhibited by 0.22 and 2.2 nM ACTH-(1-24) and ACTH-(1-39) in a dose-dependent manner. These results suggest that in the absence of negative feedback control of ACTH secretion by glucocorticoids, ACTH can regulate its secretion by inhibition of hypothalamic CRH release.

Addison Disease↗
PubMed1987

[Clinical experience of tegafur-uracil (UFT) against bladder cancer and renal cell carcinoma].

The safety of prolonged administration of UFT in which tegafur and uracil were mixed in a ratio of 1:4 in molar fraction was studied in 44 cases of bladder cancer and 10 cases of renal cell carcinoma. Daily doses of UFT were 300-600 mg, and average total doses administered were 102.0 g for bladder cancer and 116.6 g for renal cell carcinoma cases. Incidence of adverse effects were 25.0% in bladder cancer and 18.5% in renal cell carcinoma cases. Anorexia, nausea, vomiting and decrease in WBC were observed, but rates of having discontinued the administration of UFT were very low, being 9.1% in bladder cancer and 10.0% in renal cell carcinoma. Thus, UFT was considered to be tolerable during prolonged use in bladder cancer and renal cell carcinoma and also a drug in which more usefulness is expected in multidisciplinary treatments in future.

Adult↗
PubMed1987

[Clinical trial of CSF-HU (colony-stimulating factor derived from human urine: P-100) on granulocytopenia induced by anticancer therapy in urogenital cancer patients].

We examined the value of the CSF-HU preparation (colony-stimulating factor derived from human urine: P-100) to prevent or treat granulocytopenia induced by anticancer chemotherapy. Subjects were urogenital cancer patients who underwent two courses of the same chemotherapy regimen. Among these patients, we selected the subjects whose leucocyte counts were decreased to less than 2000/mm3 after the first course of anticancer chemotherapy. P-100 was administered from the following day of the end of the second course of chemotherapy at a dose of 8,000,000 units/day by intravenous drip infusion for 7 successive days. According to the global evaluation by consideration of changes in leucocyte and granulocyte counts, the utility rate by physicians was 52.4% (22/42), and that by a committee was 50.0% (18/36). No difference was seen in utility rate and efficacy rate according to P.S., cancer types and antineoplastic drugs used. Side effects were noted only in 2.3% (1/44) which was mild and transient fever. These findings suggest that P-100 is a very useful drug for prevention and/or treatment of granulocytopenia following cancer chemotherapy.

Adolescent↗
PubMed1987

Radioimmunoassay of corticotropin-releasing hormone: methodology and clinical application.

Corticotropin-releasing hormone (CRH) levels in the human plasma and cerebrospinal fluid (CSF), and those in the rat hypothalamus, peripheral and hypophyseal portal plasma were studied by a specific h/r CRH RIA and an immunoaffinity procedure. CRH levels in the plasma and CSF were low in patients with hypercortisolemia and those with hypothalamic hypopituitarism, but high in patients with hypocortisolemia except for patients with hypothalamic hypopituitarism. Plasma CRH responded to insulin-induced hypoglycemia (ITT) those with Addison's disease and those with primary hypopituitarism, but not in patients with Cushing's syndrome or in patients with hypothalamic hypopituitarism. The results suggest that the major component of plasma CRH may be of hypothalamic origin, but other extrahypothalamic tissues cannot be ruled out as minor sources of plasma CRH. In addition, the measurement of CRH levels in the plasma and CSF seems to be of value in evaluating the hypothalamic function. The short negative feedback mechanism regulating CRH release was demonstrated in humans and rats. In the absence of the long negative feedback control of ACTH secretion by glucocorticoids, ACTH originating from the pituitary may regulate ACTH secretion form the pituitary through inhibition of CRH release.

Addison Disease↗
PubMed1986

Effects of serotonin, cyproheptadine and reserpine on corticotropin-releasing factor release from the rat hypothalamus in vitro.

We investigated the effects of serotonin, cyproheptadine and reserpine on corticotropin-releasing factor (CRF) release from the rat hypothalamus, and the effect of cyproheptadine on CRF-induced adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary (AP) in vitro using a perifusion system for rat hypothalami and AP, and a rat CRF radioimmunoassay. Cyproheptadine, 10(-8) M, had a direct inhibitory effect on both basal and 10(-9) M CRF-induced ACTH secretion from the rat AP in vitro. In addition, 10(-9)-10(-7) M cyproheptadine inhibited basal CRF release in a dose-dependent fashion, and also suppressed serotonin- and KCl-induced CRF release. Conversely, 10(-9)-10(-7) M reserpine failed to influence CRF release from the rat hypothalamus. These results indicate that a serotonergic mechanism may be involved in the CRF-releasing mechanism, and inhibition of depolarization-dependent calcium entry into cells and/or nerve endings. In addition an anti-serotonergic mechanism is involved in the inhibitory action of cyproheptadine.

Adrenocorticotropic Hormone↗