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Biomedical subjects

K Totsune

Publications and source records attributed to K Totsune.

At least 55 records · Page 3Linked to original sources
PubMed1995

Melanin-concentrating hormone in human and rat.

Melanin-concentrating hormone (MCH) is a neuropeptide originally isolated from chum salmon pituitaries. To explore physiological roles of MCH in mammals, we studied the regional distribution of immunoreactive MCH in the rat tissues and the presence of immunoreactive MCH in human adrenal glands, adrenal tumors and plasma by radioimmunoassay, and the expression of MCH mRNA in rat tissues and human brain tissues by Northern blot analysis. Immunoreactive MCH was present in every region of rat brain and neurointermediate lobe of the pituitary gland, with the highest concentrations found in the hypothalamus (48.3 +/- 6.6 pmol/g wet weight, mean +/- SEM, n = 6). The immunoreactive MCH in rat hypothalamus, frontal lobe, and pons and medulla oblongata was eluted in the position of synthetic human/rat MCH in reverse-phase high-performance liquid chromatography. No immunoreactive MCH was detected in the rat peripheral tissues. Northern blot analysis showed that a single species of MCH mRNA (approximately 1 kb) was expressed specifically in the rat and human hypothalamus, but not detectable in other regions of brain or rat peripheral tissues. Immunoreactive MCH was not detected in human adrenal glands (< 0.5 pmol/g wet weight, n = 9) or adrenal tumors including pheochromocytomas. Immunoreactive MCH were not detected in plasma obtained from human healthy subjects (< 0.25 pmol/l) and rat (< 0.25 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Renal effects of high-dose natriuretic peptide receptor blockade in rats with congestive heart failure.

Previous studies suggest that elevated plasma atrial natriuretic peptide (ANP) levels participate in regulating renal excretory function in rats with congestive heart failure (CHF). To define the role of natriuretic peptides (NPs) in the regulation of renal function in CHF, the renal responses to HS-142-1 (HS), a potent NP receptor antagonist, were studied in anesthetized rats subjected to coronary ligation that developed left ventricular infarction and CHF or in sham-operated (SO) control rats. Plasma ANP levels averaged > 14-fold higher in rats with CHF than in SO rats. In response to HS (20 mg/kg IV bolus), both mean arterial pressure and renal vascular resistance increased in rats with CHF but not in SO rats; glomerular filtration rate (GFR, 1.26 +/- 0.04 versus 0.76 +/- 0.11 mL/min) and renal plasma flow rate (RPF, 3.52 +/- 0.27 versus 2.70 +/- 0.32 mL/min) were significantly reduced in rats with CHF; and in SO rats, GFR (1.26 +/- 0.06 versus 1.20 +/- 0.07 mL/min) and RPF (3.98 +/- 0.21 versus 3.99 +/- 0.18 mL/min) were not significantly affected by HS. The sodium excretion rate (0.18 +/- 0.04 to 0.06 +/- 0.01 muEq/min) and fractional sodium excretion (0.01 +/- 0.02% to 0.04 +/- 0.01%) also fell markedly after HS administration in rats with CHF, but these parameters were unchanged in SO rats. These data indicate that NPs play a critical role in maintaining renal hemodynamic function and inhibiting tubule sodium reabsorption in rats with CHF, thus opposing sodium retention and preserving sodium balance in this model.

Animals↗
PubMed1995

Adrenomedullin in human brain, adrenal glands and tumor tissues of pheochromocytoma, ganglioneuroblastoma and neuroblastoma.

Adrenomedullin is a potent vasodilator peptide that was isolated from human pheochromocytoma. But the presence of adrenomedullin in the brain has not been clarified. We studied the presence of adrenomedullin in the human brain obtained at autopsy from 6 subjects by radioimmunoassay, as well as in the human adrenal glands and tumor tissues of pheochromocytoma, ganglioneuroblastoma and neuroblastoma. Immunoreactive adrenomedullin was detected in every region of human brain examined (0.26-1.4 pmol/g wet weight) with the highest concentrations found in thalamus (1.40 +/- 0.39 pmol/g wet weight, mean +/- SEM) and hypothalamus (1.28 +/- 0.48 pmol/g wet weight). Reverse phase high performance liquid chromatography showed that the immunoreactive adrenomedullin in the human brain was eluted in the position of synthetic human adrenomedullin 1-52. High concentrations of immunoreactive adrenomedullin were found in human adrenal glands (12.6 +/- 1.0 pmol/g wet weight, n = 7), pheochromocytoma (4.5 +/- 1.5 pmol/g wet weight, n = 11), ganglioneuroblastoma (2.0 +/- 1.3 pmol/g wet weight, n = 4) and neuroblastoma (0.55 +/- 0.21 pmol/g wet weight, n = 3). The present study has shown that adrenomedullin is present in the human brain in high concentrations, suggesting that adrenomedullin acts as a neurotransmitter, neuromodulator or neurohormone in man.

Adrenal Gland Neoplasms↗
PubMed1995

Three cases of clinical or preclinical Cushing's syndrome due to adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia: pituitary-adrenocortical function and immunohistochemistry.

We performed pituitary-adrenocortical function test and analysis of plasma steroids in three cases of adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia, and examined the plasma cortisol response to meal and oral glucose in two cases. On pathological examination, nodules were mainly composed of clear cells and some nests of compact cells were observed. Immunohistochemistry of steroidogenic enzymes showed positive P-450C17 only in the compact cells and positive 3 beta-hydroxysteroid dehydrogenase only in the clear cells. These cases were similar to clinical or preclinical Cushing's syndrome due to adenoma in both pituitary-adrenocortical function and plasma steroid patterns, but different from adenoma cases in the distribution of steroidogenic enzymes.

Adenoma↗
PubMed1995

[Cerebellin in the cerebellum in spinocerebellar degeneration].

To clarify the possible pathophysiological role of cerebellin in spinocerebellar degeneration, immunoreactive cerebellin was measured in the postmortem brain of 4 patients with spinocerebellar degeneration and 4 controls. Three other representative neuropeptides, corticotropin releasing hormone (CRH), neuropeptide Y and somatostatin, were also measured. Significant decreases in the concentration of immunoreactive cerebellin and immunoreactive CRH were found in the cerebellar hemisphere in spinocerebellar degeneration, suggesting an important pathophysiological role of cerebellin and CRH in this group of diseases. No such decreases were found in neuropeptide Y or somatostatin.

Adult↗
PubMed1995

Immunoreactive endothelin in the human kidney: comparison with natriuretic peptides.

The presence of immunoreactive endothelin (IR-ET) was studied by radioimmunoassay in human kidney with and without clinical renal failure, and the levels were compared with those of three natriuretic peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Kidney tissues were obtained at autopsy from three subjects with renal disorders (diabetic nephropathy, renal tubular necrosis, and end-stage kidney disease). Normal renal tissue was obtained at surgery from two patients with renal cell carcinoma. IR-ET was detected in three diseased kidneys obtained at autopsy (0.101 +/- 0.043 pmol/g wet weight, mean +/- SD) but not in tissues of two normal kidneys obtained at surgery (< 0.015 pmol/g wet weight). Reverse-phase HPLC showed that most of the IR-ET in the kidney (> 90%) was eluted in the position of ET-1. IR-ANP (0.23 +/- 0.06 pmol/g wet weight), IR-BNP (1.15 +/- 0.94 pmol/g wet weight), and IR-CNP (0.44 +/- 0.16 pmol/g wet weight) were detected in all samples examined. Higher concentrations of IR-BNP were found in three diseased kidneys obtained at autopsy (1.70 +/- 0.83 pmol/g wet weight vs. mean in two normal kidney tissues, 0.32 pmol/g wet weight). Such increases were not observed in IR-ANP or IR-CNP. These findings indicate that IR-ET is present in the human diseased kidney even in end-stage disease, with high concentrations comparable to those of natriuretic peptides. This raises the possibility that the production of ET-1 and BNP is increased in kidneys of patients with renal disorders.

Aged↗
PubMed1994

Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity in human hypothalamus: co-localization with arginine vasopressin.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel hypothalamic peptide consisting of 38 amino acids (PACAP1-38) with a potent stimulatory action on adenylate-cyclase in rat pituitary. The presence of PACAP-like immunoreactivity in human brain was studied by radioimmunoassay. Co-localization of PACAP with arginine vasopressin and oxytocin was investigated by immunocytochemistry in the human hypothalamus. Immunoreactive PACAP was detected in all regions of human brain (cortex, thalamus, hypothalamus, pons and hemisphere of cerebellum) with the highest levels found in the hypothalamus (8.5 +/- 1.9 pmol/g wet weight, n = 4, mean +/- S.E.M.). High performance liquid chromatography of the human hypothalamic extract showed that approximately 50% of the immunoreactive PACAP was eluted in the position of PACAP1-38. Immunocytochemical studies showed the presence of PACAP immunoreactive neurons in the paraventricular and supraoptic nuclei of human hypothalamus. PACAP co-localized with arginine vasopressin in magnocellular cells of these nuclei. These findings suggest that PACAP1-38 plays important physiological roles in the human hypothalamus.

Aged↗
PubMed1994

Immunoreactive C-type natriuretic peptide in human adrenal glands and adrenal tumors.

C-type natriuretic peptide (CNP) in human adrenal glands and adrenal tumors was measured with a specific radioimmunoassay for CNP. Tissue immunoreactive (IR-) CNP concentrations were 0.54 +/- 0.40 pmol/g wet tissue (gwt) (mean +/- SD) in 14 pheochromocytomas, 0.69 +/- 0.19 pmol/gwt in six adrenocortical tumors, and 0.49 +/- 0.22 pmol/gwt in seven normal adrenal glands (cortex and medulla mixed). These concentrations were comparable to those found in tissues from human brains. Sephadex G-50 superfine column chromatography and reverse-phase high performance liquid chromatography revealed that IR-CNP in normal adrenal glands and pheochromocytoma consisted of at least two components: a component in low molecular weight form chromatographically identical to CNP-22 and the other, a high molecular weight form very similar to human CNP-53. This study has shown that IR-CNP is present in human adrenal glands and adrenal tumors with similar molecular forms and comparable concentrations to those in the human brain.

Adenoma↗
PubMed1994

C-type natriuretic peptide in the human central nervous system: distribution and molecular form.

The distribution and molecular form of C-type natriuretic peptide (CNP) in the human central nervous system were studied with a specific radioimmunoassay for CNP-22. Immunoreactive (IR-) CNP was detectable in all regions of the brain examined (cerebral cortex, thalamus, hypothalamus, pons, and cerebellum) (0.21-0.81 pmol/g wet tissue, n = 4). The highest concentration of IR-CNP was found in the spinal cord at 1.83 +/- 0.13 pmol/g wet tissue (mean +/- SD, n = 3). Reversed-phase high performance liquid chromatography revealed a major peak migrating at the position corresponding to synthetic human CNP-53 and minor peaks comigrating with synthetic CNP-22 and the methionine-oxidized form of CNP-22, respectively. These findings suggest that IR-CNP is widely present in the human central nervous system mainly in a high molecular weight form as the major component and in the molecular form of CNP-22 as the minor component.

Aged↗
PubMed1994

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↗
PubMed1994

Endothelin in chronic renal failure.

Plasma concentrations of IR endothelin are elevated in patients with chronic renal failure. But its exact causes have not been clarified. Hypertension may be one of the most important factors associated with elevated plasma IR endothelin concentrations, although it still remains to be determined whether hypertension is a result or a cause of the elevated plasma IR endothelin concentrations in patients with chronic renal failure. Elevation of plasma IR endothelin concentrations was found in hemodialysis patients with rHuEPO-induced blood pressure elevation. Endothelin may be one of the causes in rHuEPO-induced hypertension in some hemodialysis patients. Endothelin receptors have been cloned, and several endothelin antagonists have been reported. The studies using clinically useful endothelin antagonists will further clarify the pathophysiology of endothelin in patients with chronic renal failure.

Amino Acid Sequence↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗