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K Takekoshi

Publications and source records attributed to K Takekoshi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas.

OBJECTIVE: To understand the molecular mechanisms by which catecholamine synthesis is controlled in pheochromocytomas--tumors that synthesize and release catecholamines, which are related to various clinical manifestations of the condition. METHODS: We measured the concentrations of mRNA coding for the catecholamine-synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) and for the catecholamine contents in 12 pheochromocytomas and 12 normal adrenal medullas. RESULTS: The mean content of total catecholamine and the beta-actin mRNA expression in the pheochromocytomas were almost the same as those in the normal adrenal medullas. However, the tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas were greater than those of the normal adrenal medullas. Conversely, the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas. These differences are responsible for the difference in the proportions of catecholamines between pheochromocytomas and normal adrenal medullas. The constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in magnitude among the pheochromocytomas, and the tyrosine hydroxylase mRNA expressions correlated with the contents of total catecholamine in the tumors (r=0.964, P<0.0001). CONCLUSIONS: These findings indicate that catecholamine production in pheochromocytomas is primarily controlled by the level of gene expression.

Adrenal Gland Neoplasms↗
PubMed1998

Identification and initial characterization of stathmin by the differential display method in nerve growth factor-treated PC12 cells.

The differential display of mRNA is a new strategy to identify genes that are differentially expressed under altered conditions. We applied this method to determine differential gene expression in the rat pheochromocytoma cell line during differentiation induced by nerve growth factor (NGF). Three different mRNA species were isolated, and their differential expression was confirmed by RT-PCR. One of the mRNA species was identified as stathmin, a 19 kDa cytosolic protein attracting increasing interest for its role in signal transduction. In the NGF-treated PC12 cells, the expression of stathmin mRNA increased in a time-dependent manner, as assessed by northern blot analysis and RT-PCR. We also assessed by northern blot analysis how the expression of stathmin mRNA was altered in human pheochromocytomas (n = 5) compared with that in normal adrenal medulla tissue (n = 5). The mRNA concentrations were found to be significantly greater in the pheochromocytomas than in the normal tissues. It has been shown that stathmin mRNA concentrations are increased in various tumor cells. As pheochromocytomas are well-differentiated tumors of neural origin, it is not unexpected that stathmin mRNA is overexpressed in these tumors. Stathmin was isolated and identified as a differentially expressed gene by the differential display method in PC12 cells during differentiation induced by NGF. In addition, stathmin mRNA was found to be overexpressed in human pheochromocytomas. The mechanisms responsible for the up-regulation of stathmin mRNA during differentiation of PC12 cells and the significance of its overexpression in human pheochromocytomas remain to be determined.

Adrenal Gland Neoplasms↗
PubMed1996

Failure to find associations of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia.

This study aimed to replicate positive associations between polymorphisms of the neurotrophin-3 gene and schizophrenia. The reported associations, which were the results of searching for mutations in the locus in schizophrenics under the hypothesis of neurodevelopmental etiology of schizophrenia, are that the states carrying the (CA)23 allele of the CA repeat in the first intron have a 2.56-fold increased risk of schizophrenia and those carrying the allele Glu-63 instead of Gly-63 have a 2.6-fold increased risk of schizophrenia with onset before 25 years and with duration of the illness of more than 10 years. We analyzed these polymorphisms in 80 schizophrenics with onset before 25 years of age and with duration of illness of more than 10 years and 80 age-matched psychosis-free controls. With our sample size, there was a 90% chance of detecting odds ratios observed in initial positive reports. We found similar allele and genotype frequencies of both polymorphisms between the schizophrenic and control groups. We failed to support associations between the polymorphisms of the neurotrophin-3 gene analyzed and schizophrenia.

Adult↗
PubMed1995

[Expression of mRNAs coding for catecholamine synthesizing enzymes in human adrenal pheochromocytoma].

Pheochromocytomas synthesize and release catecholamines, which subsequently are related to various clinical manifestations of the disease. However, pheochromocytomas are not innervated and the catecholamine release and synthesis are not initiated by neural impulses. It is still unknown how catecholamine synthesis is regulated in pheochromocytomas. As a first step toward understanding the molecular mechanisms by which catecholamine synthesis is controlled in the tumor, we measured the levels of mRNA coding for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines in 6 pheochromocytomas and 2 normal adrenal glands. The TH mRNA level was overexpressed and the catecholamine contents were high in 4 out of 6 pheochromocytomas. There was a close correlation between the TH mRNA level and the catecholamines content in the tumors. We also examined the gene expression of the messengers of other catecholamine synthesizing enzymes, dopamine beta-hydroxylase (DBH) and aromatic 1-amino acid decarboxylase (AADC) in pheochromocytomas. The expression of these genes was in parallel with that of TH mRNA in the tumors. These findings indicate that catecholamine overproduction in pheochromocytomas is mediated by the overexpression of genes coding for catecholamines synthesizing enzymes, TH, DBH, and AADC.

Adrenal Gland Neoplasms↗
PubMed1994

Effect of intrahepatic portal-systemic shunting on hepatic ammonia extraction in patients with cirrhosis.

Increased plasma ammonia levels in patients with advanced cirrhosis have been attributed to reduced conversion of enteric ammonia to urea by the diseased liver and to entry of enteric ammonia into systemic circulation by way of portal-systemic shunts. Because single-pass extraction is high for portal venous ammonia, reduction of portal blood supply to hepatocytes may have detrimental effects on the hepatic extraction of ammonia. To assess how the development of intrahepatic portal-systemic shunts alters hepatic ammonia metabolism, we determined portal and hepatic venous ammonia levels along with measurements of intrahepatic portal-systemic shunts using 99mTc-macroaggregated albumin in 46 patients with portal hypertension. Hepatic venous ammonia levels in the groups of patients with idiopathic portal hypertension, Child class A cirrhosis and Child class B or C cirrhosis were 36 +/- 17, 75 +/- 26 and 93 +/- 52 micrograms/dl, respectively, in increasing order, and portal venous ammonia extraction rates as calculated with the equation (portal venous ammonia-hepatic venous ammonia)/portal venous ammonia x 100% were decreased in the same order (77% +/- 14%, 50% +/- 21%, 40% +/- 25%, respectively). Furthermore, we noted a significant negative correlation between the intrahepatic shunt indexes as calculated by counts per minute in lungs/counts per minute in lungs and liver x 100% and the ammonia extraction rates. It was noteworthy that among Child class C patients, the ammonia extraction rates were significantly lower in patients with high intrahepatic shunt indexes than in those with low shunt indexes. These results demonstrate a significant direct relationship between hepatic ammonia extraction rates and intrahepatic shunting in cirrhosis.

Adult↗
PubMed1994

Anti-shock effect of pituitary adenylate cyclase activating polypeptide (PACAP) on experimental endotoxin shock in dogs.

Effects of pituitary adenylate cyclase activating polypeptide with 38 amino acid residues (PACAP-38) on both cardiovascular functions and plasma hormone levels during endotoxin shock were studied in anesthetized dogs. When PACAP-38 (a bolus 420 pmol/kg injection or a bolus 420 pmol/kg injection followed by a continuous 30 pmol/kg/min infusion for 60 min) was administered intravenously 5 min after application of endotoxin, both mean arterial pressure and cardiac output were restored at 10 min. The continuous administration of PACAP-38 was more effective in improving the symptoms of shock. Plasma adrenalin and cortisol levels were significantly increased by both regimens. These results clearly indicate that the anti-shock properties of PACAP-38 may be attributed to its abilities to increase plasma cortisol and adrenalin levels and to stimulate cardiac function.

Animals↗
PubMed1994

Pertussis toxin pretreatment enhances catecholamine secretion induced by pituitary adenylate cyclase-activating polypeptide in cultured porcine adrenal medullary chromaffin cells: a possible role of the inositol lipid cascade.

We determined how pertussis toxin (PTX) pretreatment alters PACAP-induced catecholamine secretion in cultured porcine adrenal medullary cells. Pretreatment of these cells with PTX (1 ng/ml for 24 h or 10 ng/ml for 6 h) markedly enhanced PACAP-induced catecholamine secretion. PTX pretreatment also produced a small increase in basal secretion and secretion in response to nicotine and carbachol, but the effect of the PACAP-induced secretion was most striking. We examined the role of the phosphoinositol cascade in potentiating the PACAP-induced catecholamine secretion by PTX and found that PACAP-induced accumulation of inositol phosphates in PTX-pretreated cells was significantly greater than that in untreated cells. Furthermore, removal of extracellular Ca2+ and addition of Ca2+ channel blockers inhibited the catecholamine secretion induced by PACAP in PTX-pretreated cells. From these results, we speculate that a PTX-sensitive G-protein tonically inhibits phospholipase C. PTX enhances the PACAP-induced secretion of catecholamine by blocking the action of this inhibitory G-protein.

Adenylate Cyclase Toxin↗
PubMed1994

[Zinc and selenium metabolism in liver cirrhosis].

The liver plays an important role in the metabolism of trace minerals. Hypozincemia has been well documented in cirrhotic patients and multiple mechanisms, including poor intake and depressed absorption, appear to be responsible for it. Of particular interest is a role of zinc deficiency in hepatic encephalopathy and the therapeutic potential of zinc supplementation in patients with liver cirrhosis. Although some reports indicate beneficial effects of oral zinc supplementation in cirrhotic patients with hepatic encephalopathy, not all studies have been positive. Serum selenium concentration depends on the amount of selenium ingested and the decreased levels found in cirrhotic patients should be interpreted with caution.

Humans↗
PubMed1993

Effect of NG-nitro-L-arginine on shock induced by endotoxin and by platelet activating factor in dogs.

When NG-nitro-L-arginine, a nitric oxide synthase inhibitor, administration was started 5 min prior to shock induction in anesthetized dogs, a partial restoration was observed in endotoxin-induced shock and a complete recovery in platelet activating factor (PAF)-induced shock. When NG-nitro-L-arginine infusion was started 5 min after shock induction, no significant recovery was observed in endotoxin-induced shock and a complete recovery in PAF-induced shock. These data indicate that enhanced production of nitric oxide by vascular endothelial cells may contribute to endotoxin- or PAF-induced shock and also that some mediators including inducible nitric oxide synthase and/or cellular damage might be involved in endotoxin-induced shock.

Amino Acid Oxidoreductases↗
PubMed1993

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system were examined. When PACAP-38 (270 or 420 pmol/kg body weight) was administered intravenously to the anesthetized dogs, both mean arterial pressure and left ventricular systolic pressure increased within 2 min after a temporal depression. Pulmonary arterial systolic pressure increased promptly. These hemodynamic values and heart rates (HR) 5 min after injection were significantly higher than the corresponding values in physiological saline injected dogs, and some effects were still sustained over 15 min. Cardiac output and stroke volume also increased and the values at 5 min were significantly higher than those in controls. The high dose of PACAP-38 (420 pmol/kg) evoked greater responses than those induced by the low dose (270 pmol/kg). Plasma adrenaline, but neither noradrenaline nor dopamine concentration significantly increased 15 min after injection of 420 pmol/kg PACAP-38. Moreover, PACAP-38 clearly stimulated cyclic AMP production in rat cardiac myocytes with EC50 of 1.5 x 10(-9) M and plasma cAMP levels significantly and dose-dependently increased in dogs 5 min after administration. These results first demonstrated that PACAP has inotropic and chronotropic actions on the heart possibly by a direct stimulation of adenylate cyclase in cardiac myocytes and also that the cardiovascular functions may be possibly modified by an evoked adrenaline secretion in vivo.

Animals↗
PubMed1993

[The effect of NG-nitro-L-arginine administration on the hemodynamics and plasma hormone levels during endotoxin shock in dogs].

Although various mediators such as platelet activating factor, anaphylatoxin and cytokines are considered to be involved in the pathology of endotoxin-induced shock, an endothelium-derived relaxing factor (EDRF), nitric oxide (NO) or its related substance, has recently been shown as a vasodilating factor that is produced from L-arginine. On the other hand, NG-nitro-L-arginine (L-NNA) is shown to inhibit NO production from L-arginine. Thus, in order to examine a possible involvement of NO in the shock, the effect of L-NNA administration was studied on the hemodynamics and plasma hormone levels during endotoxin-induced shock in anesthetized dogs. Twenty-five mongrel dogs were divided into the following 5 groups; (1) In group C, only physiological saline was administered. (2) In group L, a bolus injection of L-NNA (4 mg/kg B.W.) was followed by a continuous infusion of the agent (0.05 mg/kg B.W./min) for 120 min. (3) In group E, lipopolysaccharide (LPS) E. Coli 011:B4 2.625 mg/kg body weight was administered. (4) In group LE, L-NNA administration (bolus and continuous) the same as in group L was started 5 min before the injection of LPS. (5) In group EL, L-NNA administration (bolus and continuous) was started 5 min after the injection of LPS. In Group LE, MAP decreased to -45.9 mmHg 5 min after LPS injection and -33.0 mmHg 120 min from pre-level. The levels of MAP from 15 to 90 min were significantly higher than those in Group E. In Group EL, MAP decreased to -61.4 mmHg 5 min after LPS injection and this low level (-59.5 mmHg) continued for 120 min. A protecting effect of L-NNA against LPS-induced hypotension was clearly observed only when administration of the agent was started before LPS injection. These results indicated that LPS induced shock could be produced by a possible increase of NO production in the vascular endothelial cells. The other finding in the present experiment using anesthetized animals was that L-NNA had a stimulatory action on some endocrine systems such as the renin-aldosterone system and pituitary-adrenal axis, although the exact mechanism of this action of L-NNA on such systems was unclear.

Adrenocorticotropic Hormone↗
PubMed1993

[Measurements of serum pituitary hormones and dynamic tests to evaluate the pituitary functions].

Hormones produced by the anterior pituitary have conventionally been measured in the serum by radioimmunoassays (RIA), whereas more sensitive immunoradiometric assays (IRMA) have now been developed and are replacing RIA. Dynamic tests (stimulatory tests and suppression tests) rather than single and random determinations are often important tools in the study of pituitary functions. Stimulatory tests (such as glucagon plus propranolol test for growth hormone and water deprivation test for arginine-vasopressin) are used to evaluate hypofunction and suppression tests (such as dexamethasone suppression test for adrenocorticotrophic hormone) are used to investigate hyperfunction. This chapter, mainly dealing with representative dynamic tests, describes test protocols and how to interpret test results.

Adrenocorticotropic Hormone↗
PubMed1990

Increased endothelin concentration in CSF from patients with subarachnoid hemorrhage.

A considerable quantity of endothelin-like immunoreactivity was demonstrated as present in the CSF of patients with subarachnoid hemorrhage. The endothelin levels in the CSF raised from 0.4 +/- 0.2 (Mean +/- SD) pmol/L at Day 0-1 to 2.2 +/- 0.6 pmol/L at Day 6 and the levels decreased gradually. The result suggest that endothelin may contribute the generation of vasospasm often observed in subarachnoid hemorrhage.

Endothelins↗