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T Kamada

Publications and source records attributed to T Kamada.

At least 181 records · Page 10Linked to original sources
PubMed1996

Angiotensin I-converting enzyme insertion/deletion polymorphism: potential significance in nephrology.

Angiotensin I-converting enzyme (ACE) plays a pivotal role in cardiovascular homeostasis and by activating angiotensin I into angiotensin II and inactivating bradykinin. These two peptides play antagonistic roles on the cardiovascular system by regulating vascular tone and vascular smooth muscle cell proliferation. Identification of the ACE gene as a genetic marker for various forms of cardiovascular disease is a recent result of the progress made in molecular biology and genetics. The insertion/deletion (ID) polymorphism of the ACE gene defined by the presence or absence of the 287 base pair Alu sequence situated in intron 16 has been investigated as a possible genetic marker for a variety of cardiovascular disease including myocardial infarction, essential hypertension, cardiomyopathy, and diabetic vascular complications. This paper reviews prior reports and briefly describes our recent study on the association of the ACE I/D polymorphism and antiproteinuric effect of ACE inhibitors in patients with proteinuria.

Cardiovascular Diseases↗
PubMed1996

Sodium ionophore converts growth manner of vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVES: Vasoconstrictor peptides such as endothelin (ET) cause hypertrophy of vascular smooth muscle cells (VSMC) in Wistar Kyoto rats (WKY) and hyperplasia in spontaneously hypertensive rats (SHR). They also induce an increase in Na+ concentration ([Na+]i) and activate protein kinase C (PKC) independently. Therefore, we tested the hypothesis that the increase in [Na+]i may be involved in the conversion of growth manner under activated PKC in SHR VSMC. METHODS AND RESULTS: 10(-7) M phorbol ester (TPA) increased the diameter and protein content of VSMC from both strains under 18% serum conditions. Further addition of 10(-6) M gramicidin (Na+ ionophore) converted TPA-induced hypertrophy to hyperplasia, which was due to the quick transition from S to G2/M phase, only in SHR VSMC. Western blot analysis showed that serum- and TPA-induced tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was potentiated by 10(-6) M gramicidin in SHR. [Na+]i, which was measured by sodium-binding benzofuran isophthalate (SBFI), was increased about 35 mM by 10(-6) M gramicidin in both strains, but TPA did not affect basal [Na+]i and the gramicidin-induced increase in [Na+]i. CONCLUSIONS: We conclude that sodium ionophore may convert hypertrophy to hyperplasia synergistically with activated PKC in SHR VSMC, possibly by MAP kinase phosphorylation.

Animals↗
PubMed1996

[Molecular approach for analyses of gut function: an overview].

This paper reviewed recent progress in analyses of gut function by the aid of molecular biology. Particularly noted were 1) involvement of immediate early genes in mucosal epithelial proliferation in vitro and in ulcer healing in rat stomach in vivo; and 2) possible involvement of c-kit/stem cell factor, endothelin-receptor B, endothelin-3 and ret in regulation of gut motility and Hirschsprung's disease. These cases show that molecular biology, together with novel approaches through medical engineering, significantly expands our knowledge on regulation of gut functions.

Animals↗
PubMed1996

[Tuberculosis found among foreigners and treated at the National Hiroshima Hospital or Hiroshima Anti-Tuberculosis Association].

In this study, we investigated 31 foreign patients who had been diagnosed as having pulmonary tuberculosis at the National Hiroshima Hospital or Hiroshima Anti-Tuberculosis Association between 1982 to 1995. Their age ranged from 17 to 63 years, and all of them had been in Japan for less than five years. Twelve of the patients came from South America, 18 from Asia, and one from Egypt. Seven Peruvians had been infected in a tuberculosis outbreak. The reasons of their immigration were job-seeking (14 out of 31), education (8 out of 31), and marriage to Japanese men (6 out of 31). None of them were illegal immigrants. In four women who had married Japanese men, various symptoms such as cough, sputum, and slight fever came on during pregnancy, however, none of them had been diagnosed as having tuberculosis, and consequently they had received no medication during pregnancy. In 6 out of the 8 patients who were college students, their sputa were negative for tubercle bacilli, and they could be treated by chemotherapy as outpatients. In provincial cities, every effort should be made to detect tuberculosis among members of the foreign community who are living under different environments and conditions.

Adolescent↗
PubMed1995

Transfection of N-acetylglucosaminyltransferase III gene suppresses expression of hepatitis B virus in a human hepatoma cell line, HB611.

beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked oligosaccharides and forms a bisecting GlcNAc structure. Although the biological meaning of the bisecting GlcNAc structure remains unclear, it is known that the attachment of a bisecting GlcNAc inhibits further processing of oligosaccharides by other glycosyltransferases. To investigate whether or not structural changes of oligosaccharides affect secretion and gene expression of hepatitis B virus (HBV), we introduced the GnT-III gene into a human hepatoma cell line, HB611, which secreted HBV-related proteins into the medium. Positive transfectants were cloned by hygromycin resistant selection. Three clones have high activities of GnT-III and secreted lower levels of HBV-related proteins into the medium in comparison with other clones. These clones showed marked suppression of HBV-related mRNAs and an increased binding with E-PHA as judged by lectin blot. Expression of beta actin, alpha fetoprotein, albumin, and prealubmin was not correlated with GnT-III activity in all the seven clones. Treatment of these cells with tunicamycin or swainsonine resulted in enhanced expression of HBV-related mRNA. These results indicate that some glycoproteins whose oligosaccharide structures are changed by over-expression of GnT-III suppress HBV gene expression.

Blotting, Northern↗
PubMed1995

Phosphatase toward MAP kinase is regulated by osmolarity in Madin-Darby canine kidney (MDCK) cells.

We have reported that MAP kinase and its activator were activated by increase in extracellular osmolarity in Madin-Darby canine kidney (MDCK) cells [J. Clin. Invest. 93 (1994) 2387-2392]. The activation of MAP kinase quickly disappeared when cells in hypertonicity were shifted to isotonicity. Present study was planned to elucidate the mechanism for the inactivation of MAP kinase when osmolarity decreased. Combination of two different phosphatase inhibitors, 10(-6) M okadaic acid and 0.2 mM sodium orthovanadate, blocked the inactivation of MAP kinase after the decrease in osmolarity. We also demonstrated that phosphatase toward MAP kinase was activated in response to the decrease in osmolarity. These results suggest that MAP kinase is inactivated by phosphatase that is activated when osmolarity decreased.

Animals↗
PubMed1995

The role of radiotherapy in the management of spinal cord glioma.

PURPOSE: To determine the role of radiotherapy in the management of spinal cord gliomas. METHODS AND MATERIALS: Thirty-six patients with spinal cord glioma treated between 1979 and 1993 were examined. The patients had 13 astrocytic tumors (7 astrocytomas, 4 anaplastic astrocytomas, 2 glioblastomas), 22 ependymal tumors (18 ependymomas, 4 myxopapillary ependymomas), and 1 unclassified glioma. Fifteen of the patients were treated by surgery alone, but the remaining 21 patients also received postoperative radiotherapy. Total resection was performed on 1 astrocytoma and 13 ependymomas. In general, 40-50 Gy/16-20 fractions/4-5 weeks were given after parital resection, but no radiotherapy was given after total resection. RESULTS: Actuarial survival was significantly better for patients with ependymal tumors than for those with astrocytic tumors (p = 0007), 5-year actuarial survival rates being 96% and 50% for patients with ependymal tumors and astrocytic tumors, respectively. For patients with ependymal tumors, there was no difference in motor function and survival between those with total resection and those with partial resection followed by radiotherapy. Actuarial 3-year survival was 80% for patients with astrocytomas and 40% for those with anaplastic astrocytomas plus glioblastomas. The difference in the degree of motor function between the patients treated with radiotherapy and those without radiotherapy was not statistically significant. One anaplastic astrocytoma and one glioblastoma patient have lived longer than 4 years after radical treatment including radiocordectomy, or irradiation using doses larger than the tolerance threshold of the spinal cord. CONCLUSION: Postoperative conventional radiotherapy is indicated after less than total resection of low-grade ependymal tumors and astrocytomas but not after total resection of ependymomas. Radiocordectomy may be an option for certain cases with high-grade astrocytic tumors.

Adolescent↗
PubMed1995

Expression of CD38 gene, but not of mitochondrial glycerol-3-phosphate dehydrogenase gene, is impaired in pancreatic islets of GK rats.

Goto-Kakizaki (GK) rat, a rodent model of spontaneously occurring non-insulin dependent diabetes mellitus (NIDDM), exhibits impaired glucose-stimulated insulin secretion. To explore the background of the beta-cell dysfunction in NIDDM, we investigated whether and how the expression pattern of factors that would potentially be involved in the glucose-stimulated insulin secretion machinery is changed in GK rats. Using quantitative reverse transcription-PCR (RT-PCR) method, we found that the gene expression of CD38, a type 2 membrane protein which has ADP-ribosyl cyclase activity, is reduced by approximately 50% in islets of GK rats. Despite previous studies showing reduction in the FAD-linked mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity in GK rats, the mGPDH mRNA amounts were equal to those in the control Wistar rats, suggesting a difference that arose post-transcriptionally. These observations support the idea that multiple defects of the glucose-responsive insulin secreting machinery are involved in the development of diabetes in GK rats.

ADP-ribosyl Cyclase↗
PubMed1995

Assessment of autonomic function in traumatic quadriplegic and paraplegic patients by spectral analysis of heart rate variability.

We analyzed by means of autoregressive spectral analysis the spontaneous beat-to-beat heart rate variability (HRV) of quadriplegic and paraplegic male subjects at rest in the supine position. In agreement with our previous study, in nine of 15 quadriplegic patients only the high-frequency (HF: center frequency = respiratory frequency) component (a marker of vagal modulation of heart rate) was observed. In contrast, in six of the quadriplegic patients both the HF component and the low-frequency (LF: center frequency at approx. 0.1 Hz, 0.03-0.15 Hz in this study) component (a marker of sympathetic and vagal modulation of heart rate) were observed. However, in six quadriplegic patients who presented the LF component, (i) the center frequency of the LF component was lower than that in 10 healthy, sedentary, age-matched males (control I) (P < 0.01), (ii) the power of the HF component was smaller than that in the control-I group (P < 0.01) and (iii) the LF/HF power ratio (an index of sympathovagal balance) was larger than that in the control-I group (P < 0.05). On the other hand, in nine paraplegic patients with an intact 1st-4th thoracic spinal cord, from which the cardiac sympathetic nerves originate, the total power, the power of the LF component and that of the HF component were smaller than those in nine healthy, sedentary, age-matched males (control II) (P < 0.05, P < 0.01 and P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Beneficial effects of inhibition of angiotensin-converting enzyme on ischemic myocardium during coronary hypoperfusion in dogs.

BACKGROUND: Angiotensin-converting enzyme (ACE) produces angiotensin II, causing vasoconstriction of coronary arteries and reduction of coronary blood flow. The present study was undertaken to test the hypothesis that an ACE inhibitor increases coronary blood flow and improves myocardial metabolic and contractile functions of ischemic myocardium. METHODS AND RESULTS: In 65 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When cilazaprilat (3 micrograms/kg per minute) was infused into the bypass tube for 10 minutes after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 30 +/- 1 to 43 +/- 2 mL/100 g per minute despite there being no changes in coronary perfusion pressure (43 +/- 1 mm Hg). The ratio of myocardial endocardial flow to epicardial flow increased during an infusion of cilazaprilat. Both fractional shortening and lactate extraction ratio of the perfused area were increased (fractional shortening: 4.1 +/- 0.6% to 8.9 +/- 0.6%, P < .001; lactate extraction ratio: -55.7 +/- 3.3% to -36.7 +/- 3.9%, P < .001). During an infusion of cilazaprilat, the bradykinin concentration of coronary venous blood was markedly increased. The increased coronary blood flow due to cilazaprilat was attenuated by HOE-140 (an inhibitor of bradykinin receptors; coronary blood flow: 35 +/- 2 mL/100 g per minute), and by N omega-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase; coronary blood flow: 34 +/- 2 mL/100 g per minute). Intracoronary administration of bradykinin mimicked the beneficial effects of cilazaprilat. Cyclic GMP content of the coronary artery was increased by cilazaprilat compared with the untreated condition in the ischemic myocardium. In the denervated hearts, the increased coronary blood flow due to cilazaprilat was not attenuated. On the other hand, CV11974, an inhibitor of angiotensin II receptors, slightly increased coronary blood flow to 34 +/- 2 from 30 +/- 1 mL/100 g per minute. CONCLUSIONS: We conclude that an inhibitor of ACE can increase coronary blood flow and ameliorate myocardial ischemia, primarily due to accumulation of bradykinin and production of nitric oxide from the ischemic myocardium. Inhibition of angiotensin II production due to inhibition of ACE partially contributes to coronary vasodilation in the ischemic myocardium.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Group II phospholipase A2 activates mitogen-activated protein kinase in cultured rat mesangial cells.

Group II phospholipase A2 (PLA2) is a mediator of inflammation in various disease including glomerulonephritis. We recently found that urinary excretion of PLA2 was increased in patients with mesangial proliferative glomerulonephritis and that interleukin-1 (IL-1) enhanced platelet derived growth factor-stimulated mesangial cell proliferation through the action of group II PLA2 secreted in response to IL-1 stimuli. Here we report signal transducing mechanism through group II PLA2 in mesangial cells. Group II PLA2 (1-15 U/ml) rapidly activated mitogen-activated protein (MAP) kinase. IL-1 beta activated MAP kinase in two phases and the slow activation in the late phase, proceeding in parallel with increased group II PLA2 secretion elicited by IL-1 treatment, was inhibited by the specific antibody raised against group II PLA2. This suggests that the late phase activation of IL-1-induced MAP kinase was mediated, at least in part, by secreted group II PLA2.

Animals↗
PubMed1995

Roles of alpha 1-adrenoceptor activity in the release of nitric oxide during ischemia of the canine heart.

The difference in end-products of the nitric oxide, i.e., nitrate-plus-nitrite, in the coronary arterial and venous blood was increased during coronary hypoperfusion of the canine heart (12.8 +/- 0.6 vs. 2.2 +/- 0.2 microM at the baseline). Norepinephrine from sympathetic nerve endings in the heart is released due to ischemic stress, however the relation of norepinephrine with nitric oxide is unknown during ischemia. Neither beta- or alpha 2-adrenoceptor antagonists attenuated the release of nitric oxide during coronary hypoperfusion. An intracoronary infusion of an alpha 1-adrenoceptor antagonist attenuated the release of nitric oxide during coronary hypoperfusion (5.3 +/- 0.4 microM), and the attenuation of alpha 1-adrenoceptor activity further decreased coronary blood flow during hypoperfusion. These findings suggest that alpha 1-adrenoceptor activity contributes to the mechanisms whereby nitric oxide is released from the ischemic myocardium.

Animals↗
PubMed1995

Plasma nitric oxide end products are increased in the ischemic canine heart.

Coronary arteriovenous difference in stable end-products of nitric oxide metabolism, nitrate and nitrite, was increased in ischemic canine hearts. In accordance with the reduction of coronary blood flow by 40, 67, 80 and 100%, the plasma nitrate+nitrite concentration increased from 3.2 +/- 0.6 to 8.7 +/- 1.3, 12.5 +/- 1.8, 15.9 +/- 2.7, and 20.2 +/- 2.3 microM, respectively. The plasma nitrate+nitrite concentrations were further elevated during reperfusion. Administration of NG-nitro-L-arginine methyl ester decreased the production of both nitrate+nitrite and coronary blood flow; the former was restored by the concomitant administration of L-arginine. These findings suggest that the increases in the nitric oxide production result from the action of nitric oxide synthase during myocardial ischemia and reperfusion, decreasing coronary vascular resistance and attenuating myocardial ischemia.

Animals↗
PubMed1995

Transforming growth factor beta up-regulates expression of the N-acetylglucosaminyltransferase V gene in mouse melanoma cells.

beta-1,6-N-acetylglucosaminyltransferase V (GnT-V) (EC 2.4.1.155) that catalyzes beta-1,6 branching in asparagine-linked oligosaccharides is activated on viral or oncogenic transformation and is associated with tumor metastasis. To study the molecular mechanisms involved in regulation of expression of the GnT-V gene, we cloned cDNA and genomic DNA for the enzyme (Saito, H., Nishikawa, A., Gu, J., Ihara, Y., Soejima, Y., Sekiya, C., Niikawa, N., and Taniguchi, N. (1994) Biochem. Biophys. Res. Commun. 198, 318-327). We found that transforming growth factor beta (TGF beta) specifically induced GnT-V expression in mouse melanoma cells. The activity of GnT-V was increased 24 h after the addition of TGF beta and remained at high levels up to 72 h. Northern blot analysis showed that the mRNA levels of GnT-V were consistent with the increased activity. To further investigate the nature of the induction, mRNA stability and transcriptional activity were assayed. The enhancement of the GnT-V mRNA expression resulted from prolonged mRNA stability, not from increased transcription. Consequently, elevated mRNA levels were observed even 72 h after the addition of TGF beta. Lectin blot analysis involving leukoagglutinin showed newly synthesized beta-1,6 branching structures in the sugar chains of a protein of approximately 130 kDa at 48 h after TGF beta treatment. These results suggested that TGF beta caused changes in the sugar chains of proteins in melanoma cells by up-regulating GnT-V expression.

Animals↗
PubMed1995

Ubiquitous, but variable, expression of two alternatively spliced mRNAs encoding mouse homologues of transcription factors E47 and E12.

Two basic helix-loop-helix (bHLH) transcription factors, E47 and E12, are involved in cell-specific gene expression as part of dimeric complexes which interact with the cis-acting motif E-box. Although both generated from a single gene (E2A) by means of alternative splicing, the structural difference in these bHLH regions between the two suggests that the two bHLH proteins may differ in some of their functions. As a step toward elucidating the individual implications of E47 and E12, we investigated the mRNA expression ratios of their homologues (A1 and kA1, respectively) in mouse tissues and cell lines. Both the A1 and kA1 mRNAs were ubiquitously expressed in all tissues examined. However, their ratios varied: e.g., skeletal muscle, 2.2 +/- 0.3 (mean +/- SE); spleen, 2.0 +/- 0.2; pancreatic islet cells, 1.2 +/- 0.2. The A1/kA1 ratios in the cell lines investigated were similar to those of their original tissues. In conclusion, the ubiquity in mRNA expression observed for both the E47 and E12 homologues in mouse provides support for their involvement in a broad range of transcriptional regulation. The variation in the A1/kA1 expression ratios, on the other hand, supports the idea that A1 (E47) and kA1 (E12) each have some unique roles in the functions of these E2A gene-encoded bHLH proteins.

Alternative Splicing↗
PubMed1995

Noninvasive assessment of left ventricular relaxation using continuous-wave Doppler aortic regurgitant velocity curve. Its comparative value to the mitral regurgitation method.

BACKGROUND: The most established parameters of left ventricular (LV) relaxation are peak negative value of the first derivative of LV pressure (-dP/dtmax) and the time constant of isovolumic LV pressure fall. The instantaneous pressure gradient between the aorta and the LV during diastole can be calculated from the continuous-wave Doppler aortic regurgitant velocity spectrum. Because the fluctuation of aortic pressure during LV isovolumic relaxation is negligibly minor and because LV minimal pressure is negligibly low, LV pressure during the isovolumic relaxation period may be derived from the continuous-wave Doppler aortic regurgitant velocity spectrum. This study was designed to clarify whether analysis of continuous-wave Doppler aortic regurgitation recording provides accurate measures of LV relaxation over a wide range of LV function and to determine comparative values of aortic and mitral regurgitation methods in the assessment of LV relaxation. METHODS AND RESULTS: In eight mongrel dogs with acute ischemic LV dysfunction, the continuous-wave Doppler aortic regurgitant velocity spectrum was recorded simultaneously with high-fidelity LV and aortic pressures, while the continuous-wave Doppler mitral regurgitant velocity spectrum was recorded simultaneously with high-fidelity left atrial and LV pressures. The aortic regurgitant velocity spectrum was provided for the determination of Doppler-derived mean rate of LV pressure fall in 20 ms after the onset of aortic regurgitation (delta P/delta t-AR) and the time interval from the onset of aortic regurgitation to the point at (1-1/e)1/2 of the maximal aortic regurgitant velocity as an estimate of the time constant. The mitral regurgitant velocity spectrum was provided for Doppler-derived mean rate of LV pressure fall in 20 ms after the point of -dP/dtmax (delta P/delta t-MR) and the time interval from the point of -dP/dtmax to the point with mitral regurgitant velocity of (1/e)1/2 of the mitral regurgitant velocity at the point of -dP/dtmax as an estimate of the time constant. delta P/delta t-AR and delta P/delta t-MR correlated well with catheter-derived -dP/dtmax (r = .92, r = .98, P < .01, respectively). The time constant derived from aortic and mitral regurgitant velocity spectra (tau-AR and tau-MR) also correlated well with catheter-derived time constant (r = .84, r = .76, P < .01, respectively). However, a mean difference of the catheter-derived time constant minus tau-MR was larger than tau-AR (29 +/- 30 versus 4 +/- 17 ms, P < .01, presented as mean +/- 2 SD). CONCLUSIONS: LV relaxation can be assessed from the continuous-wave Doppler aortic regurgitant velocity spectrum. The aortic regurgitation method provides an even more accurate estimate of the time constant compared with the mitral regurgitation method, particularly in the presence of LV dysfunction.

Animals↗
PubMed1995

Characterization of nodules induced by bioactive glass on cultured periodontal-ligament fibroblasts.

We previously reported that materials leached from bioactive glass (BG) and vitamin D3 induced the formation of nodules on cultured periodontal-ligament fibroblasts (PLF). In this study, we have investigated the relationship between the conditions of the materials and nodule formation, analyzed morphologically, and also studied whether the production of nodules was specific to cultured PLF. PLF and skin fibroblasts were cultured in the presence or absence of BG. The amounts of calcium, phosphate, sodium and silicon in the culture medium and the number of nodules were measured at the 55th day. The nodules were observed microscopically and analyzed using an X-ray microanalyzer. In PLF, nodules were formed regardless of the presence or absence of BG; however, they were more numerous in the presence of BG. In skin fibroblasts, nodules were not observed. The amounts of calcium and silicon were higher in the presence of BG, while the amount of phosphate was lower. The nodules appeared crystalline with a spongy structure and contained calcium and phosphorus. Our results show that the nodules were associated with PLF and precipitated by the materials (higher concentrations of calcium and silicon), and they were spongy crystal composed of calcium and phosphorus.

Biocompatible Materials↗