Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 685 records · Page 38Linked to original sources

PubMed1994

Different roles of 8-hydroxyguanine formation and 2-thiobarbituric acid-reacting substance generation in the early phase of liver carcinogenesis induced by a choline-deficient, L-amino acid-defined diet in rats.

The present study was performed to assess the roles of hepatocellular oxidative damage to DNA and constituents other than DNA in rat liver carcinogenesis caused by a choline-deficient, L-amino acid-defined (CDAA) diet by examining the effects of the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD). The parameters used for cellular oxidative damage were the level of 8-hydroxy-guanine (8-OHGua) for DNA and that of 2-thiobarbituric acid-reacting substance (TBARS) for constituents other than DNA. A total of 40 male Fischer 344 rats, 6 weeks old, were fed the CDAA diet for 12 weeks with or without DPPD (0.05, 0.10 or 0.20%) or butylated hydroxytoluene (BHT, 0.25%). In the livers of the rats, the numbers and sizes of glutathione S-transferase (EC 2.5.1.18) placental form (GSTP)- and/or gamma-glutamyltransferase (GGT, EC 2.3.2.2)-positive lesions and levels of 8-OHGua and TBARS were determined. The GSTP-positive lesions of 0.08 mm2 or larger were all stained positively for GGT as well in cross-sectional area, whereas the smaller lesions were generally negative for GGT. DPPD and BHT reduced the size of the GSTP-positive lesions without affecting their total numbers. At the same time, they reduced TBARS generation without affecting 8-OHGua formation in DNA. The present results indicate that oxidative DNA damage (represented by 8-OHGua formation) and damage to constituents other than DNA (represented by TBARS generation) may play different roles in rat liver carcinogenesis caused by the CDAA diet; the former appears to be involved in the induction of phenotypically altered hepatocyte populations while the latter may be related to the growth of such populations.

Animals↗

PubMed1994

Antitumor effect of intratumoral administration of biological response modifiers: induction of immunosuppressive acidic protein, a type of alpha 1-acid glycoprotein, in mice.

The antitumor effects of biological response modifiers (BRMs) in an experimental mouse model, the "double grafted tumor system" were analyzed. Male BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on the right flank (10(6) cells) and left flank (2 x 10(5) cells) on day 0, and BRMs were injected intratumorally into the right tumor on days 3, 4 and 5. PSK (a protein-bound polysaccharide preparation), interleukin-1 (IL-1) and cepharanthin (CR) cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG and tumor necrosis factor (TNF) cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) and IL-6 inhibited neither the right nor the left tumor. Immunosuppressive acidic protein (IAP) in serum was increased transiently soon after intradermal injection of PSK, CR, OK-432 and TNF in BALB/c mice. Lentinan, however, did not induce IAP. IAP in serum was gradually increased after intradermal inoculation of Meth-A tumor in BALB/c mice. The biochemical difference between PSK-induced IAP (early, inflammatory IAP) and Meth-A-induced IAP (late, tumor-induced IAP) was investigated by crossed affinity immunoelectrophoresis with concanavalin A. IAP of murine serum was separated into 4 peaks. IAP in normal mouse was rich in high-mannose type sugar chain (Peak 3) and contained no hybrid-type sugar chain (Peak 4), which was present in inflammatory and tumor-induced IAP. Inflammatory IAP was rich in biantennary sugar chain (Peak 2) and tumor-induced IAP was rich in tri-tetraantennary sugar chain (Peak 1).

Animals↗

PubMed1994

Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults.

We investigated the role of monocyte/macrophage-activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and of interferon-gamma (IFN-gamma). These levels returned to almost normal during remission. Neither interleukin-4 nor granulocyte/macrophage colony-stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). Serum concentrations of soluble CD8 and soluble interleukin-2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T-cells obtained from patients with active HLH spontaneously secreted M-CSF and IFN-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma and M-CSF at least partly from T-cells, such as CD8+ T-cells, might contribute to activation of monocytes or histiocytes, resulting in the up-regulated monokine production and haemophagocytosis in HLH.

Adolescent↗

PubMed1994

Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes.

A circulating form of the membrane-bound ICAM-1 (CD54), a ligand for lymphocyte function-associated antigen-1 (LFA-1), has recently been identified in normal human serum. In this study, serum levels of soluble ICAM-1 (sICAM-1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis and chronic active hepatitis (autoimmune) showed significant elevations in sICAM-1 compared with normal healthy subjects. The median level in PBC was approximately seven-fold above normal. Significant elevations in sICAM-1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC, sICAM-1 levels were related to summary assessment of disease severity (Child-Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E-selectin did not differ significantly from healthy controls. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM-1, investigation of ICAM-1 gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM-1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM-1 in this disease. Similar increases in ICAM-1 mRNA expression were found in cultured, concanavalin A (Con A)-stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression of ICAM-1 and the secretion/shedding of sICAM-1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may be an important source of sICAM-1 in autoimmune and other chronic liver diseases. The possible role of sICAM-1 in inflammatory disorders remains to be determined.

Adolescent↗

PubMed1994

Radionuclide evaluation of the uretero-ileoceco-proctostomy (ileocecal rectal bladder).

Technetium 99m diethylenetriaminepentaacetic acid renoscintigraphy was applied to 14 patients to obtain comprehensive information on the kidney and urinary tract 12.6 +/- 8.8 months (mean +/- SD) after uretero-ileoceco-proctostomy (ileocecal rectal bladder) diversion. The total glomerular filtration rate (GFR) was within the normal range in all patients, and the diuretic renogram was normal in 19 of 28 kidneys, dilated-nonobstructive in 7 and obstructive-intermediate in 2. The mean colonic reflux was 16.6 +/- 18.4% of total excretion and the mean total residual in the colon and rectum was 38.8 +/- 15.5%. In the second study, performed 12.4 +/- 3.5 months later in 9 patients, the GFR of bilateral and individual kidneys remained stable, 17 of 18 kidneys were normal as judged by both renography and pyelography, and the occurrence and degree of colonic reflux decreased. There was a tendency for the rectal capacity to increase, while the total residual tended to decrease solely due to the decrease in colonic residual. These results indicate that the ileocecal rectal bladder functions well as an internal continent reservoir and that radionuclide investigation is a valuable and cost-beneficial means of follow-up of urinary diversions.

Aged↗

PubMed1994

Comparison of symptomatic and asymptomatic reinfarctions after small subcortical stroke.

We compared possible factors leading to symptomatic and asymptomatic reinfarcts in 207 patients an average of 2.1 years after their index atherothrombotic stroke presenting with small subcortical infarcts. Symptomatic reinfarcts were mostly small infarcts in the perforating artery regions associated with angiographic evidence of atherosclerosis of parent arteries (large-artery disease), a high hematocrit, elevated fibrinogen and Lp(a) levels. They occurred with insufficient inhibition of platelet aggregability in patients receiving antiplatelet medication. In contrast, many asymptomatic reinfarcts were small perforator infarcts not associated with large-artery disease or cortical infarcts, and occurred in the absence of hematologic risk markers, and in spite of sufficient inhibition of platelet aggregability.

Aged↗

PubMed1994

Effect of gender on the left ventricular diastolic performance during isometric handgrip exercise in normal individuals.

To evaluate the effects of gender and isometric handgrip exercise on left ventricular diastolic function in normal individuals, atrial and rapid filling fraction were investigated using M-mode echocardiography in 35 postmenopausal women and 31 age-matched men. There were no significant differences in heart rate, mean blood pressure, atrial filling fraction, and rapid filling fraction at rest between women and men. When the amount of change in hemodynamic variable during exercise was compared, there were no significant differences in heart rate and mean blood pressure between women and men. But the increase in atrial filling fraction and the decrease in rapid filling fraction were significantly larger in women than in men. These data suggest that left ventricular diastolic function is restricted in postmenopausal women, and left atrial booster pump action is mobilized when afterload is increased during isometric handgrip exercise.

Aged↗

PubMed1994

Effect of ventriculoarterial coupling on residual left ventricular pump function in diabetic patients with myocardial infarction.

To study the ventriculoarterial coupling in diabetic patients with myocardial infarction (MI), 26 diabetic and 34 nondiabetic patients were investigated using radionuclide angiography in the 3rd week after acute MI. Effective arterial elastance was nearly one half of left ventricular end-systolic elastance in nondiabetic patients. On the other hand, effective arterial elastance was twice left ventricular end-systolic elastance in diabetic patients. These data suggest that a decrease in left ventricular contractility and an increase in effective arterial elastance lead to increased potential energy and decreased work efficiency in diabetic patients.

Arteries↗

PubMed1994

Association analysis of restriction fragment length polymorphism for alpha 2-adrenergic receptor genes in essential hypertension in Japan.

Recently, restriction fragment length polymorphism (RFLP) of alpha 2-adrenergic receptor gene (alpha 2-C10) digested with Bsu36I restriction enzyme has been reported in US populations. Therefore, we examined the association of this RFLP with essential hypertension by comparing the frequency of specific alleles for this gene in Japanese populations. The distribution of this RFLP was compared with that in US populations. Subjects were hypertensive patients with a family history of essential hypertension (n = 56) and normotensive subjects whose parents had no history of essential hypertension (n = 46). DNA was prepared from leukocytes. RFLP was determined by use of Southern blot analysis with an alpha 2-C10 probe and Bsu36I. The frequencies of the major (12-kb) and minor (5.8-kb) alleles were 0.30 and 0.70 in hypertensive patients and 0.38 and 0.62 in normotensive subjects, respectively. The difference between observed alleles in all subjects in each group was not significant (chi 2 = 1.33, P > .1). The difference between the overall allelic frequency in Japan and that reported in US populations was significant. This study found no evidence for an association between alpha 2-adrenergic receptor gene/Bsu36I RFLP and essential hypertension in Japan. However, the findings showed that the allele frequency in Japan differed from that reported in US populations.

Adult↗

PubMed1994

Molecular mechanism of adipogenic activation of the angiotensinogen gene.

Angiotensinogen gene expression is controlled in a tissue- and development-specific manner. Interestingly, the angiotensinogen gene is abundantly expressed in adipose tissues other than the liver, where it is mainly produced. We investigated the molecular mechanism of angiotensinogen gene expression in a 3T3-L1 preadipocyte-adipocyte system. Although angiotensinogen mRNA was barely detectable in preadipocytes, its levels increased significantly during differentiation. As a whole, the pattern of the change in transcriptional activity of the angiotensinogen promoter was similar to that of the angiotensinogen mRNA levels during adipogenic differentiation, indicating that the activation of the angiotensinogen promoter might be involved in the adipogenic differentiation-coupled gene expression. The proximal promoter region, from -96 to +22 of the transcriptional start site, was sufficient to confer adipogenic activation, and the proximal element from -96 to -52 of the transcriptional start site was necessary for this promoter stimulation. DNA-protein binding experiments showed that this proximal element specifically bound to a nuclear factor induced by adipogenic differentiation. These results suggest that the proximal promoter element from -96 to -52 plays a role in adipogenic activation of the angiotensinogen promoter.

3T3 Cells↗

PubMed1994

Angiotensinogen as a risk factor for essential hypertension in Japan.

A common molecular variant of angiotensinogen (AGT), the precursor of the potent vasoactive hormone angiotensin II, has been incriminated as a marker for a genetic predisposition to essential hypertension in Caucasians (Jeunemaitre, X., F. Soubrier, Y. V. Kotelevtsev, R. P. Lifton, C. S. Williams, A. Charru, S. C. Hunt, P. N. Hopkins, R. R. Williams, J. M. Lalouel, and P. Corvol. 1992. Cell. 71:169-180). We now show that the same variant, T235, is associated with essential hypertension in Japanese patients. The observation of this association in a distinct, ethnically homogeneous population further substantiates an involvement of angiotensinogen in the pathogenesis of essential hypertension and has physiological, epidemiological, and evolutionary implications.

Adolescent↗

PubMed1994

Molecular mechanism of transcriptional activation of angiotensinogen gene by proximal promoter.

Angiotensinogen is shown to be produced by the liver and the hepatoma cell line HepG2. As a first step for understanding the molecular relationship between the transcriptional regulation of the angiotensinogen gene and the pathogenesis of hypertension, we have analyzed the basal promoter of the angiotensinogen gene. Chloramphenicol acetyltransferase (CAT) assays with 5'-deleted constructs showed that the proximal promoter region from -96 to +22 of the transcriptional start site was enough to express HepG2-specific CAT activity. Electrophoretic mobility shift assay and DNase I footprinting demonstrated that the liver- and HepG2-specific nuclear factor (angiotensinogen gene-activating factor [AGF2]) and ubiquitous nuclear factor (AGF3) bound to the proximal promoter element from -96 to -52 (angiotensinogen gene-activating element [AGE2]) and to the core promoter element from -6 to +22 (AGE3), respectively. The site-directed disruption of either AGE2 or AGE3 decreased CAT expression, and the sequential titration of AGF3 binding by in vivo competition remarkably suppressed HepG2-specific CAT activity. Finally, the heterologous thymidine kinase promoter assay showed that AGE2 and AGE3 synergistically conferred HepG2-specific CAT expression. These results suggest that the synergistic interplay between AGF2 and AGF3 is important for the angiotensinogen promoter activation.

Angiotensinogen↗

PubMed1994

Mechanism of cAMP regulation of renin gene transcription by proximal promoter.

Renin is produced mainly by the kidney, and cAMP is a main positive regulator of its synthesis. This study was undertaken to analyze the molecular mechanism of cAMP-mediated regulation of Ren-1C gene transcription by the proximal promoter. We first showed that the promoter region from -365 to +16 of the mouse renin gene (Ren-1C) mediated the cAMP-induced chloramphenicol acetyltransferase gene expression in embryonic kidney-derived 293 cells. Deletion analysis and heterologous promoter assay disclosed that the proximal promoter region from -75 to +16 was able to activate chloramphenicol acetyltransferase expression by cAMP, and indicated that the proximal promoter element from -75 to -47 (RP-2 element) overlapping the TATA-like region was able to confer cAMP responsiveness. Electrophoretic mobility shift assay and DNase I footprinting analysis demonstrated that novel nuclear factors in 293 cells interacted with the RP-2 element, and that cAMP increased the binding activity of these nuclear factors to the RP-2 element. Furthermore, we demonstrated that cAMP enhanced the binding of nuclear factors derived from juxtaglomerular cells, the main production site of renin in the kidney, to the RP-2 element in vivo. These results suggest that the RP-2 element plays an important role in the cAMP-mediated regulation of Ren-1C gene transcription through the proximal promoter.

Base Sequence↗

PubMed1994

The protective effect of preconditioning on reperfusion-induced arrhythmia is lost by treatment with superoxide dismutase.

The purpose of this study was to investigate the relation between free radicals and the effect of preconditioning on reperfusion arrhythmias using the isolated working rat heart model. Rats were divided into 3 groups: control, preconditioned without superoxide dismutase (SOD) and preconditioned with SOD (n = 8 each group). The incidence of reperfusion-induced ventricular fibrillation (Vf) in the preconditioned without SOD group was reduced from 100% to 13% (p < 0.005 vs control). This protective effect of preconditioning was not observed in the SOD-treated group (incidence of Vf increased from 13% to 75%, p < 0.025). The protective effect of preconditioning on reperfusion arrhythmias is related to the presence of oxygen free radicals which occur during the reperfusion period of the preconditioning phase.

Animals↗

PubMed1994

Improvement of regional wall motion in medically treated myocardial infarction with single-vessel coronary artery disease.

Long-term changes in regional wall motion (RWM) following acute myocardial infarction (AMI) in 42 patients with uncomplicated single-vessel disease were examined retrospectively by repeat cardiac catheterizations. The first and second cardiac catheterizations were performed at an average of 28 days and 6.6 years after the onset of AMI, respectively. All 42 patients underwent first and second cardiac catheterizations without undergoing coronary artery bypass surgery or coronary angioplasty. Regional left ventricular functions were analyzed by the centerline method using a right anterior oblique left ventriculogram. The wall motion abnormality score (WMAS) was defined as [# chord below -2SD] x [mean SD chord below -2SD]. The improvement in the WMAS was more prominent in cases with an occluded infarct-related artery. Thus, we concluded that 1) RWM improves significantly with medical treatment in long-term follow-up in cases of uncomplicated AMI with single-vessel disease, and 2) the improvement of RWM is completed within the first few weeks after AMI in cases with a patent infarct-related artery.

Adult↗

PubMed1994

Effects of NS-2, a new class 1 antiarrhythmic agent, and AFD-19, its active metabolite, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats: comparison with disopyramide and mexiletine.

We studied the antiarrhythmic effects of NS-2 (4-diisobutylamino-1,1-diphenyl-1-butanol maleate) and AFD-19 (active metabolite of NS-2) on early stage ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized male rats. These effects were compared with those of disopyramide and mexiletine. Drugs were intravenously administered either before or after coronary occlusion. When administered 5 min before occlusion, 3 mg/kg of NS-2 and AFD-19 exhibited equivalent anti-arrhythmic activity to that of 5 mg/kg of disopyramide and mexiletine, as assessed by reductions in the number of premature ventricular complexes and in the incidences of ventricular tachycardia and ventricular fibrillation. In a dose of 5 mg/kg, the antiarrhythmic effects of NS-2 and AFD-19 were more pronounced. When administered 5 min after coronary artery occlusion, only NS-2 and AFD-19 (in doses of 5 mg/kg) had significant antiarrhythmic effects. None of the drugs influenced the severe ventricular arrhythmias induced by reperfusion when administered 1 min before reperfusion. In conclusion, NS-2 might be effective in reducing the severity of the life-threatening ventricular arrhythmias that occur during acute myocardial infarction.

Amino Alcohols↗

PubMed1994

Genetic characterization of Drosophila RBP-J kappa (suppressor of hairless) as a neurogenic gene in adult PNS development.

Drosophila RBP-J kappa is a novel sequence-specific DNA binding protein encompassing the integrase motif which is highly conserved in various organisms. Its gene has been shown to be identical to Suppressor of Hairless which regulates adult peripheral nervous system (PNS) development. To elucidate the precise function of the RBP-J kappa protein in adult PNS development, we analyzed transgenic files that misexpress the RBP-J kappa protein. Such studies have shown that RBP-J kappa regulates PNS cell fate in at least two steps: commitment to sensory mother cell by lateral inhibition and terminal differentiation into the socket and shaft cells. Taken together with analysis of phenotypes of Suppressor of Hairless mutants, RBP-J kappa shows the synergistic activity with neurogenic genes.

Animals↗

PubMed1994

Species-specific expression of the hepatic renin gene.

The catalytic reaction of renin, an aspartyl proteinase, with angiotensinogen is the rate-limiting step fo the renin-angiotensin system involved in the maintenance of blood pressure and electrolyte balance in mammals. We have characterized species-specific expression of the hepatic renin gene by RNase protection experiment, primer extension analysis, and promoter assay using an in vitro DNA transfection. RNase protection experiments revealed that the renin gene is expressed in rat liver, but neither in mouse nor in human. Primer extension analysis identified the putative promoter region of the rat renin gene, which contains TATAAAA sequence, a canonical regulatory DNA element. In order to test whether the upstream region of the renin gene with respect to the putative transcription initiation site is a functional promoter, we have examined the ability of the 5'-flanking sequences of the rat renin gene as well as the human and mouse genes to activate expression of a reporter gene containing the bacterial chloramphenicol acetyltransferase (CAT)-coding sequences, by transient transfection assays. In transfected HepG2 cells, a hepatoma cell line, only the rat renin promoter was capable of driving the CAT gene expression. These results suggested that the rat-specific renin gene expression in the liver could be primarily determined by its promoter specificity.

Animals↗