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Biomedical subjects

M Sekiya

Publications and source records attributed to M Sekiya.

At least 55 records · Page 3Linked to original sources
PubMed1996

Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.

BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty.

This protocol was performed to elucidate the preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty (PTCA). A total of 118 patients with 134 vessels undergoing successful PTCA was randomly and prospectively assigned to the probucol group (group P) or the control group (group C). The subjects consisted of 91 men and 27 women, with a mean age of 63.4 +/- 2.3 years. Sixty-six vessels of 59 patients in group P and 68 vessels of 59 patients in group C were evaluated by coronary angiography at 3 months after PTCA. Probucol (0.5 mg/day) was administered between >7 days before PTCA and 3 months after PTCA. The serum total cholesterol (TC) level and the formula low-density lipoprotein cholesterol (formula LDL-C) in group P decreased from 203.8 +/- 43.1 to 169.6 +/- 39.4 mg/dl and from 131.4 +/- 0.7 to 108.7 +/- 2.5 mg/dl, whereas in group C, the levels decreased only from 202.3 +/- 32.1 to 194.2 +/- 29.8 mg/dl and from 129.2 +/- 38.1 to 124.3 +/- 31.7 mg/dl, respectively. The restenosis rate was significantly lower in group P (19.7%; 13 of 66 vessels) than in group C (39.7%; 27 of 68 vessels; p < 0.05). In group P, the probucol blood concentration was significantly higher in the subjects without restenosis (31 +/- 9 microg/ml) than in those with restenosis (18 +/- 8 microg/ml; p < 0.01), but the serum TC and formula LDL-C levels were not significantly different between these two groups. In summary, long-term administration of probucol significantly reduces the incidence of restenosis after PTCA. it was suggested that the mechanism of this preventive effect was not reducing the serum TC or formula LDL-C levels, but rather an inhibitory action on smooth muscle cell proliferation.

Adult↗
PubMed1996

Portal insulin delivery is superior to peripheral delivery in handling of portally delivered glucose.

It is still controversial as to whether physiological portal insulin delivery has metabolic advantages over peripheral insulin delivery. To clarify this issue, glycemic regulation during intravenous (IVGTT) and oral (OGTT) glucose tolerance tests and hyperglycemic clamp studies with either peripheral or portal glucose infusion was investigated in left-segmentally pancreatectomized dogs with portal ([PPx] n = 7) or systemic ([Tx] n = 7) venous drainage of the remaining pancreas. In Tx dogs, systemic diversion of pancreatic venous effluent was accomplished by gastroduodenal-caval shunt. Data obtained were compared with those in normal control dogs ([NC] n = 7). The loss of pancreatic beta-cell mass in PPx dogs decreased insulin responses to peripheral and portal glucose loads. In contrast, Tx dogs showed insulin responses comparable to those of NC dogs to glucose loads via both routes. Against peripheral glucose loads (IVGTT and hyperglycemic clamp with peripheral glucose infusion), PPx and Tx dogs showed deteriorated glucose handling. Against portal glucose loads (OGTT and hyperglycemic clamp with portal glucose infusion), deteriorated glucose handling was observed in Tx dogs, but not in PPx dogs. Deterioration in glycemic regulation against portal glucose loads in left-segmentally pancreatectomized dogs with peripheral insulin delivery but not in pancreatectomized dogs with portal delivery indicates that intraportal hyperglycemia and hyperinsulinemia are essential for promoting hepatic glucose handling.

Animals↗
PubMed1996

Captopril, an angiotensin-converting enzyme inhibitor, induced pulmonary infiltration with eosinophilia.

In this study, we investigated the association between the drug-induced pulmonary infiltration with eosinophilia (PIE) syndrome in a patient with hypertension and the angiotensin-converting enzyme inhibitor (ACE-I) captopril. Although the patient developed diffuse lung field infiltrates accompanied by productive cough and striking peripheral eosinophilia, these symptoms disappeared after termination of the administration of captopril, pronase and cephalexine. Furthermore, the results of the peripheral lymphocyte stimulation test, skin patch test and provocation test under informed consent showed a positive reaction only for captopril. Therefore, this patient was diagnosed as captopril-induced PIE syndrome.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[Usefulness of 123I-BMIPP myocardial scintigraphy for evaluation of the left ventricular function in patients with chronic heart failure].

We examined the relationship between free fatty acid metabolism using 123I beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) and cardiac function in patients with chronic heart failure (CHF). Cardiac free fatty acid metabolism was evaluated by the heart to mediastinum ratio (H/M), the heart to lung ratio (H/Lu), the heart to liver ratio (H/Li) and the myocardial uptake ratio (MUR) obtained from the planar imaging. Cardiac function was evaluated by the percent of fractional shortening (%FS) and the amount of left ventricular mass (LV mass) calculated with echocardiography. The study included 34 male and 14 female subjects of CHF with mean age of 61 +/- 9 years; dilated cardiomyopathy (DCM): n = 17, ischemic heart disease (IHD): n = 16, valvular disease: n = 5, hypertrophic cardiomyopathy: n = 4, hypertension: n = 4, amyloidosis: n = 2. The correlations between indices of BMIPP uptake and those of echocardiography were as follows: H/M vs. %FS (r = 0.67, p < 0.01), H/Lu vs. %FS (r = 0.49, p < 0.01), H/Li vs. %FS (r = 0.12, p = 0.42), MUR vs. %FS (r = 0.03, p = 0.86) and MUR/LV mass vs. %FS (r = 0.59, p < 0.01). The correlation coefficient between H/M and MUR/LV mass in patients with IHD was higher than that in patients with DCM. In conclusion, BMIPP, in particular, is a useful tool for evaluating cardiac function in patients with CHF.

Aged↗
PubMed1995

Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in diagnosis of coronary artery disease.

OBJECTIVES: The purpose of this study was to evaluate the feasibility, safety and diagnostic accuracy of thallium-201 myocardial tomography with intravenous adenosine triphosphate (ATP) infusion in patients with suspected coronary artery disease. BACKGROUND: Both ATP and adenosine are potent coronary vasodilators with a very short half-life. Several studies have confirmed that the diagnostic accuracy of adenosine thallium-201 scintigraphy is comparable to that with exercise. However, a high incidence of side effects, including atrioventricular (AV) block, has also been reported. Because the appropriate infusion rate for ATP has not yet been determined, this agent has not been tested in combination with myocardial scintigraphy. METHODS: The study group included 253 consecutive patients who underwent thallium-201 myocardial tomography with ATP infusion (0.16 mg/kg body weight per min for 5 min). The occurrence of adverse effects was carefully monitored. Of the 120 patients with coronary angiography, 76 had significant coronary artery disease. Tomographic images were assessed visually and by computer-quantified polar maps, and they were compared with the results of coronary angiography. RESULTS: Although 56% of the patients had some adverse effects, they were transient and mild. In all patients, the ATP infusion protocol could be completed, and no patient required aminophylline; AV block occurred in only 2% of the patients. The sensitivity and specificity were 88% and 80%, respectively, by visual analysis and 91% and 86%, respectively, by computer quantification. CONCLUSIONS: Thallium tomography with ATP is feasible and has a diagnostic value similar to that with adenosine for detecting coronary artery disease. In addition, it may have fewer side effects than adenosine myocardial tomography.

Adenosine Triphosphate↗
PubMed1995

IL-2-induced gene expression of protein-tyrosine phosphatase LC-PTP requires acidic and serine-rich regions within IL-2 receptor beta chain.

A protein-tyrosine phosphatase LC-PTP is preferentially expressed in hematopoietic cells and is an early response gene in lymphokine stimulated cells. Here, we found the LC-PTP mRNA induction by IL-2 was markedly inhibited by several tyrosine kinase inhibitors. The induction required both the acidic and serine-rich regions of the IL-2 receptor beta chain (IL-2R beta) in mouse IL-3-dependent pro-B BAF-B03 transfectants. This is strikingly different from the induction of c-myc gene expression, which requires the serine-rich region alone. In addition, overexpression of activated-Lck or -Raf kinases resulted in augmented LC-PTP mRNA expression in myeloid cell line 32D transfectants. Considering the previous findings that the acidic region of the IL-2R beta is responsible for association with Lck and activation of Raf kinase, IL-2-induced expression of LC-PTP mRNA may be primarily transduced through a Lck-Raf mediated signaling pathway.

Animals↗
PubMed1995

Insulin resistance in essential hypertensive patients with impaired glucose tolerance.

This study evaluated insulin secretion and insulin sensitivity in 17 non-obese hypertensive patients (aged 45.6 +/- 2.2 years, body mass index 24.0 +/- 0.5 kg/m2, mean +/- S.E.M.) with (n = 8) and without glucose intolerance (n = 9) and compared the results with those of 16 age-matched non-obese normotensive subjects with (n = 7) and without glucose intolerance (n = 9). The hypertensive patients without glucose intolerance showed a significantly lower insulin-mediated glucose disposal and a compensating increase in second-phase insulin secretion compared with normotensives without glucose intolerance. In hypertensives with glucose intolerance, insulin-mediated glucose disposal was significantly lower and second-phase insulin secretion was comparable to that in normotensives without glucose intolerance. After 3 months of angiotensin-converting enzyme (ACE) inhibition with oral administration of delapril, blood pressure was significantly reduced in the hypertensives with glucose intolerance (n = 9). The insulin-mediated glucose disposal significantly (P < 0.01) recovered from 6.0 +/- 0.81 to 8.0 +/- 0.71 mg/kg per min. The second-phase insulin secretion tended to be lower (but not significantly) but insulin clearance increased from 15.4 +/- 0.85 to 19.1 +/- 1.42 ml/min (P < 0.05). These data show that in hypertensive patients without glucose intolerance insulin resistance might compensatorily augment second-phase insulin secretion and lead to hyperinsulinemia. In hypertensives with glucose intolerance, insulin resistance might induce postprandial hyperglycemia, which leads to hyperinsulinemia because of second phase insulin secretion at a level similar to that of normotensives.

Administration, Oral↗
PubMed1995

Primary hyperparathyroidism associated with multiple myeloma.

A 73-year-old woman was diagnosed as primary hyperparathyroidism. Hypercalcemia recurred after parathyroidectomy, though serum calcium concentration temporarily resumed to normal. Hypercalcemia was eventually shown to be due to multiple myeloma. In spite of the frequent association of hypercalcemia with malignant disease and the relative frequency of primary hyperparathyroidism as a cause of hypercalcemia, primary hyperparathyroidism accompanied by multiple myeloma has been considered in only a limited number of reports. Here, the cases in the literature are reviewed and discussed.

Adenoma↗
PubMed1995

[Normal-sized ovary carcinoma syndrome: histopathological analysis of 14 cases].

Fourteen cases of "normal-sized ovary carcinoma syndrome" (diffuse metastatic malignant disease of the abdominal cavity of the female, with normal-sized ovaries, with no origin assigned definitively by intraoperative or preoperative evaluation, Feuer et al., 1989) were analyzed histologically, histochemically, immunohistochemically and ultrastructurally. Through these studies, 14 cases were divided into 11 primary peritoneal tumors (4 diffuse malignant mesotheliomas and 7 serous surface papillary carcinomas) and 3 metastatic peritoneal tumors (2 ovarian tumors and 1 appendicular tumor). To distinguish serous surface papillary carcinomas from epithelioid diffuse malignant mesotheliomas, examinations such as hyaluronidase digestion test, electron microscopy, and immunohistochemical studies using antibodies for Ber-EP4 and Vimentin were found to be useful. In order to achieve an accurate prognosis of normal-sized ovary carcinoma syndrome, it seems necessary for us to accumulate more information on this syndrome.

Carcinoma, Papillary↗
PubMed1994

Downregulation of Wilms' tumor gene (wt1) during myelomonocytic differentiation in HL60 cells.

The putative Wilms' tumor-suppressor gene (wt1) encodes a zinc finger DNA binding protein that functions as a transcription repressor. The wt1 gene expression corresponds to kidney development, suggesting a role for this gene in nephroblast differentiation. Here we show that wt1 mRNA expression was downregulated during terminal differentiation of promyelocytic HL60 cells. When HL60 cells were induced to differentiate to granulocytes by dimethyl sulfoxide (DMSO) or retinoic acid (RA), a marked downregulation in the levels of wt1 transcripts was found. The wt1 transcripts were also downregulated in HL60 cells during differentiation to monocytes by vitamin D3 or 12-o-tetradecanoyl-phorbol-13-acetate. Nuclear run-on transcription studies showed the transcriptional rate of wt1 gene was not significantly altered during DMSO-induced granulocytic differentiation, suggesting the downregulation was mostly caused by posttranscriptional modification. Importantly, wt1 transcripts were not significantly altered in K562 cells by treatments with DMSO or RA, which do not induce differentiation of K562 cells. These findings suggest that wt1 gene expression may be downregulated as a differentiation-linked event in HL60 cells.

Base Sequence↗
PubMed1994

Induction of protein-tyrosine phosphatase LC-PTP by IL-2 in human T cells. LC-PTP is an early response gene.

Tyrosine phosphorylation has been implicated in interleukin 2 (IL-2)-induced growth signaling and the phosphorylation levels are regulated by the balance of tyrosine kinase and tyrosine phosphatase activities. Here, we demonstrate the rapid activation of a leukocyte tyrosine phosphatase LC-PTP (HePTP) gene expression by IL-2 in an IL-2 dependent human T cell ILT-Mat. Accumulation of LC-PTP mRNA appeared at 1 h and peaked at 6 h after IL-2 stimulation, simultaneous with the G1 to early S phase, and the induction of LC-PTP mRNA did not require protein synthesis. LC-PTP protein increased approximately 6-fold at 8 h after IL-2 stimulation. Nuclear run-on assays showed that the induction of LC-PTP mRNA expression is mostly due to transcriptional activation. These data suggest that LC-PTP is an early response gene and its protein seems to be a crucial molecule which regulates the tyrosine phosphorylation level during T cell proliferation.

Enzyme Induction↗