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Biomedical subjects

O Murakami

Publications and source records attributed to O Murakami.

At least 73 records · Page 4Linked to original sources

Elevated plasma C-type natriuretic peptide concentrations in patients with chronic renal failure.

1. C-type natriuretic peptide is a neuropeptide, which is also produced by the vascular endothelial cells. Plasma immunoreactive C-type natriuretic peptide concentrations in patients with various diseases have not yet been studied. 2. Plasma immunoreactive C-type natriuretic peptide concentrations were studied by radioimmunoassay in normal subjects, patients with congestive heart failure, non-dialysed patients with chronic renal failure and haemodialysis patients with chronic renal failure. The C-type natriuretic peptide levels were compared with the levels of atrial natriuretic peptide and brain natriuretic peptide. 3. Plasma immunoreactive C-type natriuretic peptide concentrations were greatly elevated in patients with chronic renal failure [non-dialysed, 13.0 +/- 4.2 pmol/l (mean +/- SEM), n = 9, P < 0.01 compared with normal subjects (4.4 +/- 0.4 pmol/l, n = 26); haemodialysis, 16.1 +/- 2.1 pmol/l, n = 13, P < 0.01], but not in patients with congestive heart failure (New York Heart Association Class II-IV, 3.0 +/- 0.7 pmol/l, n = 11, P > 0.05). Plasma immunoreactive atrial natriuretic peptide and brain natriuretic peptide concentrations were elevated both in patients with congestive heart failure and in haemodialysis patients with chronic renal failure. 4. Reverse-phase high performance liquid chromatography showed that immunoreactive C-type natriuretic peptide in plasma from normal subjects and haemodialysis patients was eluted in the positions of C-type natriuretic peptide-22 and -53. 5. These findings suggest that C-type natriuretic peptide is a non-cardiac circulating hormone and participates in the cardiovascular regulation in a different manner from atrial natriuretic peptide and brain natriuretic peptide.

Adolescent↗

Natriuretic peptides in the human kidney.

We studied the presence of three natriuretic peptides--atrial natriuretic peptide (ANP), human brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)--in the human kidney by radioimmunoassay and immunocytochemistry. Immunoreactive ANP, immunoreactive human BNP, and immunoreactive CNP concentrations in six kidneys were 0.12 +/- 0.07 (mean +/- SD), 0.23 +/- 0.08, and 0.37 +/- 0.07 pmol/g wet wt, respectively. Sephadex G-50 superfine column chromatography and reversed-phase high-performance liquid chromatography of kidney extracts revealed a broad peak of immunoreactive ANP comigrating with ANP-28 and urodilatin. Renal immunoreactive human BNP consisted of three components; the major component comigrated with human BNP-32. Renal immunoreactive CNP consisted of at least two components; the major component comigrated with CNP-22, and the minor component eluted in a position similar to that of authentic human CNP-53. Immunocytochemistry showed that immunoreactive human BNP was colocalized with immunoreactive ANP in the segments of distal tubules, whereas immunoreactive CNP was found predominantly in the proximal tubules. These findings indicate that these three natriuretic peptides are present in the human kidney and raise the possibility that they form a renal natriuretic peptide system that participates in the local regulation of sodium and water transport and renal circulation in the human kidney.

Adult↗

Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity in ganglioneuroblastoma and neuroblastoma.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a 38 amino acid peptide originally isolated from ovine hypothalamus. It has a potent stimulatory action on adenylate cyclase in the rat pituitary. The presence of PACAP was studied in the tumor tissues of ganglioneuroblastoma and neuroblastoma by radioimmunoassay and immunocytochemistry. Immunocytochemical studies showed positive immunostaining in 4 out of 7 ganglioneuroblastomas and 4 out of 6 neuroblastomas. Immunoreactive PACAP concentrations in tissues of 3 ganglioneuroblastomas ranged from 14.5 to 27.8 pmol/g wet weight (20.0 +/- 5.7 pmol/g wet weight, mean +/- S.D.) and the concentration in one neuroblastoma tissue was 111.0 pmol/g wet weight. Reverse phase high performance liquid chromatography of the tumor tissue extract of ganglioneuroblastoma showed a peak eluting in the position of PACAP1-38 and smaller broad peaks eluting later. These results indicated that high concentrations of immunoreactive PACAP were present in the tumor tissues of ganglioneuroblastoma and neuroblastoma, and suggest the possibility that this peptide plays a pathophysiological role in some ganglioneuroblastomas and neuroblastomas.

Child↗

[A case of adrenal mixed tumor of pheochromocytoma and adrenocortical adenoma presenting diabetes mellitus and hypertension].

A 61-year-old woman with hyper-catecholaminemia and hyper-glucocorticoidemia due to a mixed tumor of the right adrenal gland is described. The patient, who had been medicated for hypertension since 1977, complained of thirst and general malaise in 1986. Body weight loss was remarkable. There was neither absolute truncal obesity nor moon face. In September 1986, her blood pressure was 180/110 mmHg and blood glucose level was 400mg/dl. Noradrenaline levels in plasma and in urine were remarkably elevated (1659 pg/ml and 120 micrograms/day, respectively), and adrenaline levels were also high (397 pg/ml in plasma, 34 micrograms/day in urine). Plasma cortisol and urinary 17-OHCS were elevated (39.2 micrograms/dl and 11.9 mg/day, respectively). Plasma ACTH was in the normal range (42.6 pg/ml). Oral administration of neither 1mg nor 8 mg of dexamethasone suppressed plasma cortisol or ACTH levels. Both 131I-metaiodobenzylguanidine and 131I-adosterol accumulated in the right adrenal gland. In 1987 the adrenal tumor (3.0 x 3.5 cm, 30 g) was resected. After the operation, her blood pressure and blood glucose level returned to normal, so that the medication became unnecessary. Histologically it was revealed that the tumor was a mixed adenoma consisting of adreno-medullary and cortical cells (corticomedullary adenoma). The literature on 21 cases of pheochromocytoma associated with Cushing's syndrome was briefly reviewed. Mathison (1969) reported the first case of a mixed tumor of adreno-medullary and cortical cells. So far as we know the present case is the second.

Adenoma↗

[A case of bilateral aldosterone-producing adrenal adenomas].

A 43-year-old female was admitted to our hospital for high blood pressure control. She showed hypokalemia with increased urinary potassium excretion, high plasma aldosterone concentration (33.9ng/dl, normal range; 2-12ng/dl) and reduced plasma renin activity (trace, normal range; 0.83-5ng/ml/hr). Bilateral adrenal tumors were revealed by abdominal computed tomography, and left adrenalectomy and right partial adrenalectomy were performed. Cytochromes p-450 and other enzymes involved in aldosterone synthesis were found predominantly in the tumor portions but not in the zona glomerulosa of the attached adrenals, which histopathologically showed paradoxical hyperplasia. This was a rare case of bilateral aldosterone-producing adrenal adenomas, which we could differentiate from idiopathic hyperaldosteronism by employing immunohistochemical analysis of steroidogenic enzymes.

Adenoma↗

Plasma concentrations of immunoreactive-endothelin in patients with chronic renal failure treated with recombinant human erythropoietin.

1. Elevation of blood pressure is one of the major side effects of recombinant human erythropoietin therapy in haemodialysis patients. 2. We investigated the possible involvement of endothelin in the pathogenesis of this recombinant human erythropoietin-induced blood pressure elevation in 51 patients undergoing maintenance haemodialysis. 3. Blood haemoglobin level increased from 7.1 +/- 0.1 to 8.8 +/- 0.1 g/dl (means +/- SEM) after 8 weeks of treatment with recombinant human erythropoietin (3000-4500 units/week). An increase in mean blood pressure was found in 19 patients (37%) (n = 9, by 0-10 mmHg; n = 10, by > 10 mmHg). 4. Plasma immunoreactive-endothelin concentration significantly increased from 2.26 +/- 0.18 to 3.14 +/- 0.31 pmol/l in the 10 patients whose mean blood pressure increased by more than 10 mmHg (P < 0.05), but not in the other patients. Moreover, the increase in plasma immunoreactive-endothelin concentration showed a significant positive correlation with the change in mean blood pressure in 19 patients with elevated mean blood pressure (r = 0.47, P < 0.05). 5. There was no significant correlation between the change in plasma immunoreactive-endothelin concentration and the change in blood haemoglobin level or the change in body weight. 6. These results suggest the possibility that endothelin may contribute to the recombinant human erythropoietin-related rise in blood pressure in some haemodialysis patients.

Blood Pressure↗

Endothelin in ectopic ACTH-secreting bronchial carcinoid tumors.

The presence of immunoreactive endothelin (ir-ET) in the tumor tissues of two cases of ectopic ACTH-secreting bronchial carcinoid tumors was studied by radioimmunoassay. The cross-reaction with big ET-1, ET-2, and ET-3 was 5%, 6%, and 6%, respectively. Tumor tissue ir-ET concentrations in two ectopic ACTH-secreting bronchial carcinoid tumors were 920 and 3,370 fmol/g wet weight, which were much higher than those in pheochromocytomas (146 +/- 70 fmol/g wet weight; n = 12, mean +/- SD), adrenocortical tumors (115 +/- 105 fmol/g wet weight, n = 14), and normal parts of adrenal glands (82 +/- 31 fmol/g wet weight, n = 12). High-performance liquid chromatography of the tumor tissue extract showed that the ir-ET was mainly eluted in the position of ET-1. Plasma levels of ir-ET in these two cases were not elevated (1.2 and 1.7 pmol/L). The findings of the present study suggest that ET-1 has local pathophysiologic roles in the tumor tissues of ectopic ACTH-secreting bronchial carcinoid tumors.

Adrenal Cortex Neoplasms↗

Colocalization of corticotropin-releasing factor and vasopressin in the paraventricular nucleus of the human hypothalamus.

The anatomical relationship between corticotropin-releasing factor (CRF)-containing cells and arginine vasopressin (AVP)-containing cells in the human hypothalamus was investigated by immunocytochemistry. In the paraventricular nucleus of the hypothalamus (PVH), CRF-like immunoreactivity (CRF-LI) was present exclusively in parvocellular cells, while AVP-like immunoreactivity (AVP-LI) was present in both parvocellular and magnocellular cells. No CRF-immunoreactive neurons were observed in the supraoptic nucleus. All CRF-immunoreactive parvocellular cells in the PVH were also AVP immunoreactive. We confirmed the presence of AVP in the CRF-immunoreactive cells by using two kinds of anti-AVP antisera, one of which recognized the side chain of AVP while the other recognized the ring structure of AVP. Colocalization of CRF-LI and AVP-LI was observed not only in the same perikarya but also in the same nerve fibers of parvocellular cells. The present results raise the possibility that AVP and CRF may be secreted together into the human portal circulation.

Adolescent↗

A case of ruptured dissecting aneurysm 5 years after pituitary microsurgical treatment of Cushing's disease: autopsy findings in the hypothalamic-pituitary-adrenal axis.

The patient was a 26-year-old man with Cushing's disease who underwent transsphenoidal microscopic surgery for a pituitary microadenoma. His postoperative course was uneventful, but he died suddenly five years after the operation. At autopsy, a ruptured dissecting aneurysm with marked atherosclerosis was observed in the aorta. In the pituitary, a small focus of adrenocorticotropic hormone (ACTH) producing adenoma, possibly residual adenoma, was detected and Crooke's degeneration was observed in the non-tumorous pituitary gland. But immunohistochemical patterns of pituitary hormones in the non-tumorous pituitary gland were normal and the adrenal cortex was unremarkable. In the hypothalamus, corticotropin-releasing hormone immunoreactivity was not detected and arginine vasopressin was sporadically positive. Considering these findings, this patient may have developed subclinical hypercortisolism due to the residual adenoma at the time of autopsy, despite clinical remission. Cushing's syndrome is considered to be a risk factor dissecting aneurysm, and in this case the metabolic changes in Cushing's disease may have influenced the development of the dissecting aneurysm. Periodic cardiovascular re-evaluations should therefore be performed when there is clinical remission of Cushing's syndrome.

Adenoma, Basophil↗

An ACTH-secreting bronchial carcinoid: presence of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in the tumor tissue.

The presence of three regulatory peptides, corticotropin-releasing hormone, neuropeptide Y and endothelin-1, was studied by radioimmunoassay in the tumor tissue of an ACTH-secreting bronchial carcinoid. A 36-year-old female was admitted to hospital because of moon face, central obesity and hypertension. High levels of plasma ACTH and cortisol and urinary 17-OHCS and 17-KS were found. One mg dexamethasone did not suppress plasma ACTH and cortisol levels, but 8 mg did so slightly. Corticotropin-releasing hormone (100 micrograms, iv) stimulated plasma ACTH levels (0 min; 34.8 pmol/l; 30 min; 41.1 pmol/l). The computerized tomography showed the presence of a tumor in the right lung. This lung tumor was removed surgically and has been shown by microscopical examination to be a bronchial carcinoid with ACTH-positive cells. The tumor tissue concentrations of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 were 3.34 pmol/g wet weight, 8.07 pmol/g wet weight and 0.92 pmol/g wet weight, respectively, although plasma concentrations of these three peptides were not elevated. Reverse phase high performance liquid chromatography showed that immunoreactive peptides in the tumor tissue were mainly eluted in the position of the standard peptides. These findings indicate that this case of ACTH-secreting bronchial carcinoid had high levels of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in its tumor tissue and suggested that these peptides may act locally, in a paracrine or autocrine manner, in the tumor.

ACTH Syndrome, Ectopic↗

[Evaluation of immunotoxicity tests using cyclosporin A-treated rats: the International Collaborative Immunotoxicity Study II (cyclosporin A)].

Immunotoxicological effects of cyclosporin A (CsA) were studied by enhanced histopathological and functional tests in rats. Male F344 rats were orally administered with CsA in doses of 0, 2.5, 10, and 40 mg/kg/day for 28 successive days. Hematological examination revealed that the CsA treatment brought about a marked dose-dependent decrease in the number of WBCs, which was attributed to a decrease in the number of lymphocytes. In the femoral bone marrow, a significant reduction in the number of nucleated cells was observed, which was attributed to a decrease in the number of lymphocytes and erythroblasts. Histopathologically, diminution of thymic medullas, appearance of tangible body macrophages in thymic cortices, and calcification and basophilic changes in kidneys were observed in the middle and high dose groups. Immunohistological examination with anti-rat T lymphocyte antibody showed a decrease in the number of T cells at the periarterial lymphatic sheaths in the spleens. As for the functional tests, CsA treatment remarkably reduced the PFC number even in the low dose group. The Con A response of spleen cells was decreased in the middle and high dose groups. The STM response was reduced only in the high dose group. The NK activity was little affected. Thus, in the CsA-treated F344 rats, the enhanced histopathological and some functional tests which were proposed by ICICIS, were found to be useful to detect damages to the immune system.

Administration, Oral↗

Plasma growth hormone (GH) responses to corticotropin-releasing hormone in patients with acromegaly--the effect of dexamethasone pretreatment and the comparison with GH responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and GH-releasing hormone.

It has been reported that paradoxical GH responses to corticotropin-releasing hormone (CRH) occur in only few patients with acromegaly. However, we have observed such responses in 7 of 14 active acromegalic patients. Therefore, we have studied the GH responses to thyrotropin-releasing hormone (TRH) (500 micrograms, iv), gonadotropin-releasing hormone (LHRH) (100 micrograms, iv) and GH-releasing hormone (GHRH) (100 micrograms, iv) in these patients to examine the relationships between the GH responses to CRH and the responses to these hypothalamic hormones. Further, these patients received human CRH (1-41) NH2 (100 micrograms, iv) with or without dexamethasone (Dex) pretreatment (1 mg/100 ml saline, iv, from -30 to +30 min) to study the mechanism of CRH-induced GH secretion, and a perifusion experiment was performed using adenoma tissue obtained at surgery from one patient (10(-7) M CRH and TRH were added) to elucidate whether CRH acts directly at the pituitary level. Aberrant GH responses induced by CRH were found in 7 of 14 (50%) acromegalic patients (TRH responders: 10/13, 77%; LHRH responders: 2/9, 22%; GHRH responders: 10/12, 83%). In these patients, percent GH increment induced by CRH ranged from 81 to 144% (Mean +/- SE, 118 +/- 8%), and the GH peak (19 +/- 3 min) appeared as early as after TRH (23 +/- 4 min, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma.

1. We investigated the usefulness of neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma using a simple and highly sensitive r.i.a. for human neuropeptide Y. 2. Plasma immunoreactive neuropeptide Y concentrations were measured without extraction in plasma samples (100 microliters) from patients with various diseases. 3. The plasma immunoreactive neuropeptide Y concentration in patients with phaeochromocytoma (172.3 +/- 132.4 pmol/l, mean +/- SD, n = 23) was significantly higher than that in healthy adult subjects (40.1 +/- 10.1 pmol/l, n = 40, P < 0.0001). The plasma immunoreactive neuropeptide Y concentrations in patients with ganglioneuroblastoma (590.7 +/- 563.6 pmol/l, n = 6) and patients with neuroblastoma (566.9 +/- 524.4 pmol/l, n = 15) were significantly higher than those in control children (1-9 years old, 82.2 +/- 39.9 pmol/l, n = 72, P < 0.0001). 4. The plasma immunoreactive neuropeptide Y concentration in patients with essential hypertension (34.0 +/- 3.7 pmol/l, n = 18) was within the normal range, but in patients with chronic renal failure undergoing maintenance haemodialysis (192.1 +/- 68.0 pmol/l, n = 25) and in non-dialysed patients with chronic renal failure (85.1 +/- 23.1 pmol/l, n = 7) it was significantly higher than that in healthy adult subjects (P < 0.0001). 5. Eighty-seven per cent of the patients with phaeochromocytoma, 67% of the patients with ganglioneuroblastoma and 80% of the patients with neuroblastoma showed plasma immunoreactive neuropeptide Y concentrations higher than the upper limits in the control subjects [62 pmol/l (adult) and 160 pmol/l (children)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Studies on reinforcing effects of methylephedrine, caffeine and their mixture with intravenous-self administration in rhesus monkeys].

The reinforcing effects of methylephedrine hydrochloride (ME), anhydrous caffeine (CA) and their mixture (ME+CA) were studied by the intravenous cross self-administration experiment and by the progressive ratio experiment in four male rhesus monkeys each. In the intravenous cross self-administration experiment, ME, CA and ME+CA were found to have reinforcing effects. Self-administration rates above the level of cocaine, a typical reinforcing drug, were not observed in ME or CA alone, but observed in their mixture (120 + 126 micrograms/kg/inj.: M dose or 480 + 504 micrograms/kg/inj.: H dose). The minimum reinforcing doses were 120 micrograms/kg/inj. (M dose) for ME, 126 micrograms/kg/inj.: (M dose) for CA, and ME 30 micrograms+CA 32 micrograms/kg/inj. (L dose) for the mixture. Vomiting was observed during the session in monkeys which showed higher self-administration rates of ME and the mixture, and decreases in the rates were observed in these animals on the next day. One animal at H dose of the mixture, which showed a high self-administration rate on both the 1st and 2nd days, died after the end of the session on the 2nd day. In the progressive ratio experiment, the final ratios at 120 micrograms/kg/inj. of ME, 126 micrograms/kg/inj. of CA and the mixture of ME 120 micrograms/CA 126 micrograms/kg/inj. were almost equal to or less than that of saline (negative control). Thus, these drugs didn't show reinforcing effects at the above levels. However, a reinforcing effect was observed in three out of four monkeys administered 1920 micrograms/kg/inj. of ME, 2016 micrograms/kg/inj. of CA, and the mixture of ME 1920 and CA 2016 micrograms/kg/inj.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunoreactive endothelin in urine of patients with and without diabetes mellitus.

Immunoreactive (ir)-endothelin (ET) in urine was studied with a radioimmunoassay in patients with diabetes mellitus (DM) and non-DM diseases including endocrine disorders, primary glomerular diseases, autoimmune diseases, and hematological malignancies. Twenty-four-hour excretions (mean +/- SEM) of ir-ET were 8.0 +/- 0.9 pmol/day in the DM group (n = 13) and 9.5 +/- 1.2 pmol/day in the non-DM group (n = 51). No significant differences among DM and other disease groups were noted with respect to 24-h ir-ET excretion. Reverse-phase high-performance liquid chromatography of a normal urine extract revealed a major peak eluting later than ET-1. Gel chromatography revealed a single major peak in a smaller molecular weight (MW) region in normal urine and an additional peak in larger MW region in a urine extract from a DM patient. Urinary ir-ET consists of at least two components which may be metabolites of ET or ET precursors in plasma or peptides derived from the kidney.

Adolescent↗

Immunoreactive endothelin in pheochromocytomas.

The presence of endothelin (ET) in tumor tissue and plasma of patients with pheochromocytoma was studied by radioimmunoassay. Immunoreactive (ir-) ET concentrations in 12 pheochromocytomas ranged from 66 to 253 fmol per gram wet tissue (gwt) (146 +/- 20 fmol/gwt, mean +/- SEM). These values were not significantly higher than tissue ir-ET concentrations of two primary aldosteronism (66 and 132 fmol/gwt) and three normal adrenal glands (71-120 fmol/gwt) (0.05 less than p less than 0.1). However, tumor tissue ir-ET concentrations in six of the 12 pheochromocytomas were higher than 132 fmol/gwt (the upper value of the control tissues). Sephadex G-50 column chromatography and reverse-phase high-performance liquid chromatography of pheochromocytoma tumor extracts showed a major peak eluting at an identical position to synthetic ET-1. Plasma ir-ET concentrations of pheochromocytomas (1.4 +/- 0.9 fmol/ml, n = 17) were not significantly different from those of patients with essential hypertension (1.0 +/- 0.7 fmol/ml, n = 20) and normal subjects (1.0 +/- 0.4 fmol/ml, n = 18) (0.05 less than p less than 0.1). This study has shown that high concentrations of ET-1 are present in tumor tissues of 50% of pheochromocytomas.

Adrenal Gland Neoplasms↗