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T Tatsumi

Publications and source records attributed to T Tatsumi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Involvement of transporter associated with antigen processing 2 (TAP2) gene polymorphisms in hepatitis C virus infection.

BACKGROUND & AIMS: Transporter associated with antigen processing (TAP) has essential roles in the antigen-presenting systems, translocating antigenic peptides from the cytosol into the endoplasmic reticulum. The aim of this study was to clarify whether TAP polymorphisms are involved in hepatitis C virus (HCV) infection. METHODS: The 145 HCV-infected Japanese patients examined in this study were categorized into two groups: 36 carriers with persistently normal alanine transaminase (ALT) values and 109 patients with chronic liver disease (CLD). TAP2 gene phenotypes were determined by means of polymerase chain reaction-restriction fragment length polymorphism, and their frequencies were compared between the two groups. RESULTS: Frequencies of TAP2*0101, *0102, and *0201 were not different between the two groups. However, TAP2*0103 frequency in carriers with normal ALT levels was significantly higher than that in patients with CLD (44% vs. 16%; P = 0.00064, Pc < 0.005). Although the TAP2*0103 allele was tightly linked with class II DRB1*1302-DQB1*0604 haplotype in this study, the TAP2*0103 frequency in the normal ALT group was also significantly higher than that in the CLD group even in DRB1*1302-DQB1*0604-negative patients (31% vs. 10%; P = 0.0076, Pc < 0.05). CONCLUSIONS: These findings suggest that TAP2*0103 may be closely associated with low serum ALT activity in HCV-infected Japanese patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Interleukin 1beta protects mice from Fas-mediated hepatocyte apoptosis and death.

BACKGROUND & AIMS: Fas-mediated apoptosis is one of the major death processes of hepatocytes in liver diseases. The aim of this study was to determine whether interleukin (IL)-1beta regulates the Fas-mediated apoptotic process of differentiated hepatocytes in vivo. METHODS: IL-1beta was injected into Balb/cA mice 5 hours before lethal challenge with agonistic anti-Fas administration. Survival and hepatocyte apoptotic process of these mice were examined. RESULTS: IL-1beta pretreatment prolonged animal survival in a dose-dependent manner, and 500 ng of IL-1beta completely protected mice from lethality. Both serum alanine aminotransferase value and hepatic DNA fragmentation were significantly suppressed by IL-1beta pretreatment. IL-1beta affected neither hepatic distribution of anti-Fas antibody nor Fas expression levels on hepatocytes but significantly suppressed Fas-induced activation of hepatic caspase 3-like protease. Suppression of Fas-induced activation of the caspase by IL-1beta was diminished by coadministration with D-galactosamine and reversed by coinjection with an excess amount of uridine. CONCLUSIONS: These results suggest that IL-1beta suppresses Fas-mediated hepatocyte apoptosis by inducing molecule(s) that suppress the apoptosis control machinery upstream of caspase 3. This observation raises the possibility that IL-1beta acts as a negative regulator of Fas-mediated hepatocyte apoptosis during liver injury.

Alanine Transaminase↗
PubMed1998

Energy metabolism after ischemic preconditioning in streptozotocin-induced diabetic rat hearts.

OBJECTIVES: The aim of this study was to compare the cardioprotective effects of preconditioning in hearts from streptozotocin-induced diabetic rats with its effects in normal rat hearts. BACKGROUND: The protective effect of ischemic preconditioning against myocardial ischemia may come from improved energy balance. However, it is not known whether preconditioning can also afford protection to diabetic hearts. METHODS: Isolated perfused rat hearts were either subjected (preconditioned group) or not subjected (control group) to preconditioning before 30 min of sustained ischemia and 30 min of reperfusion. Preconditioning was achieved with two cycles of 5 min of ischemia followed by 5 min of reperfusion. RESULTS: In the preconditioned groups of both normal and diabetic rats, left ventricular developed pressure, high energy phosphates, mitochondrial adenosine triphosphatase and adenine nucleotide translocase activities were significantly preserved after ischemia-reperfusion; cumulative creatine kinase release was smaller during reperfusion; and myocardial lactate content was significantly lower after sustained ischemia. However, cumulative creatine kinase release was less in the preconditioned group of diabetic rats than in the preconditioned group of normal rats. Under ischemic conditions, more glycolytic metabolites were produced in the diabetic rats (control group) than in the normal rats, and preconditioning inhibited these metabolic changes to a similar extent in both groups. CONCLUSIONS: The present study demonstrates that in both normal and diabetic rats, preservation of mitochondrial oxidative phosphorylation and inhibition of glycolysis during ischemia can contribute to preconditioning-induced cardioprotection. Furthermore, our data suggest that diabetic myocardium may benefit more from preconditioning than normal myocardium, possibly as a result of the reduced production of glycolytic metabolites during sustained ischemia and the concomitant attenuation of intracellular acidosis.

Adenine Nucleotides↗
PubMed1998

Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus.

The human leukocyte antigen is a crucial genetic factor that initiates or regulates immune response by presenting foreign or self antigens to T lymphocytes. The aim of this study was to investigate whether HLA polymorphism is associated with the onset or progression of liver injury in chronic hepatitis C virus (HCV) infection. We determined HLA class I antigens and class II alleles in 130 hepatitis C virus (HCV)-infected patients (33 carriers with persistently normal alanine transaminase [ALT] values and 97 patients with chronic liver disease [CLD]). HLA class I (A, B) was typed serologically, and class II (DRB1, DQB1) was typed by means of polymerase chain reaction-restriction fragment length polymorphism methods. The frequencies of DRB1*0405 and DQB1*0401 were higher in HCV-infected patients than in uninfected subjects. Among HCV-infected patients, the frequencies of B54, DRB1*0405, and DQB1*0401 were significantly higher in patients with CLD than in those carriers with persistently normal ALT values, whereas DRB1*1302, DRB1*1101, and DQB1*0604 were more frequently found in carriers with persistently normal ALT values than in patients with CLD. From extended haplotype analyses, in carriers with B54-DRB1*0405-DQB1*0401 haplotype, the risk of having liver injury was 13.2 times greater than in carriers with DRB1*0405-DQB1*0401 but without B54 [P = 0.0015, Haldane odds ratio = 13.2 (95% confidence interval, 1.7-103.8)]. In contrast, carriers with B44-DRB1*1302-DQB1*0604 had a 12.7-fold lower relative risk of developing liver injury compared to those with the haplotype containing B44 but not DRB1*1302-DQB1*0604 [P = 0.0076, Haldane odds ratio = 0.079 (0.009-0.695)]. Our findings show that extended haplotypes including class I B54 are closely associated with the progression of liver injury, whereas extended haplotypes including class II DRB1*1302-DQB1*0604 are associated with low hepatitis activity in chronic HCV infection.

Adult↗
PubMed1998

Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice: hepatoprotective role of TNF alpha.

Fas-mediated apoptosis is one of the major death processes of hepatocytes in liver diseases. Although compensatory regeneration occurs during liver injury, it has not been determined whether regenerating hepatocytes die by the same apoptotic process as quiescent hepatocytes. To clarify this issue, the hepatocyte apoptotic process, after injection of agonistic anti-mouse Fas, was compared between sham-operated mice and two-thirds partially hepatectomized mice. The onset of hepatocyte apoptosis was retarded in hepatectomized mice, as evidenced by both morphological and biochemical observations, resulting in significantly prolonged animal survival. Flow cytometric analysis revealed similar levels of Fas expression on hepatocytes between hepatectomized mice and sham-operated mice; however, the activation of liver caspase-3-like protease after Fas stimulation was suppressed in hepatectomized mice, whereas pro-caspase-3 expression did not change with or without hepatectomy. Anti-tumor necrosis factor alfa (TNF alpha), when administered before hepatectomy, partially reversed suppression of caspase-3-like activity after Fas stimulation. Furthermore, the injection of TNF alpha into untreated mice suppressed caspase-3-like activity and prolonged animal survival after Fas stimulation. These results indicate that Fas-signaling events at the level or upstream of caspase-3-like protease are suppressed during liver regeneration, resulting in delayed hepatocyte apoptosis, and also that TNF alpha acts as one of the protective factors against Fas-mediated hepatocyte apoptosis.

Animals↗
PubMed1998

Microbial contamination of 'sterile water' used in Japanese hospitals.

We examined the following samples of water from 10 hospitals for microbial contamination: water obtained using an ultra filtration system (UF water), a reverse osmosis system (RO water), a water distillation system (distilled water) and tap water. UF water and RO water are used for handwashing before surgery, and distilled water for the preparation of drugs. All 10 samples of tap water examined were contaminated with < 10 colony forming units (cfu)/mL. Thirteen (68%) of 19 samples of UF water, nine (53%) of 17 samples of RO water and 15 (79%) of 19 samples of distilled water were contaminated with 10(1)-10(4) cfu/mL. The majority of micro-organisms were non-fermentative bacteria such as Sphingomonas paucimobilis and CDC gr. IV C-2. Japanese hospitals commonly use UF water and RO water for preoperative handwashing under the assumption that it is sterile. Our results suggest, however, that these types of water are inferior microbiologically to tap water. Distilled water from the dispensary was also contaminated with micro-organisms. The available chlorine content of tap water was 0.17-0.42 ppm and that of UF water (from tap water) 0-0.06 ppm. There was no available chlorine in RO water or distilled water (each from tap water). The reduction or disappearance of available chlorine appears to be associated with microbial contamination of UF water, RO water and distilled water.

Chlorine↗
PubMed1998

Cross-linking of Fc(gamma)-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T-lymphocyte induction in vitro.

In hepatitis C virus (HCV) infection, immune complex (IC)-type virus particles are frequently observed in circulation. The IC leads to cross-linking of Fcgamma receptors (FcgammaR) on monocytes and exerts immunoinhibitory function. To test the roles of IC in HCV-specific cytotoxic T lymphocyte (CTL) induction, we generated HCV CTL from peripheral blood mononuclear cells of chronic hepatitis C patients with or without HCV-IC- or immunoglobulin G (IgG)-coated culture plates and compared their lytic activities. HCV-IC or adherent IgG, which induces FcgammaR cross-linking, significantly reduced CTL activity. Expression of B7-1 on monocytes decreased on adherent IgG. In addition, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) production increased from cells on adherent IgG and their mRNA expression in monocytes was enhanced. Anti-TNF-alpha antibody during induction on adherent IgG inhibited lysis; however, anti-TGF-beta completely reversed its inhibitory effect. These results demonstrated that HCV-IC or adherent IgG impaired HCV-CTL induction in vitro. The FcgammaR-mediated CTL suppression occurred via decreased expression of monocyte B7-1 and/or enhanced production of TGF-beta1.

Adult↗
PubMed1998

Plasminogen activator inhibitor-1 promoter 4G/5G genotype is not a risk factor for myocardial infarction in a Japanese population.

There is little question that the blood clotting process is triggered and causes the vascular occlusion associated with myocardial infarction. Although it is less clear what part blood coagulation events might play in the etiology of coronary artery disease, impaired regulation of anticoagulation or fibrinolysis might be involved. Among anticoagulant and fibrinolytic factors, an elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration has been identified as a risk factor for the development of myocardial infarction. An association between one polymorphism of the PAI-1 promoter (4G/5G single nucleotide deletion/ insertion at position -675) and plasma PAI-1 levels was described in 1995. However, most recent studies seem to point to the lack of such an association. This is the first report on the frequency of this polymorphism in the Japanese population with respect to the risk of myocardial infarction. Sixty-six patients with myocardial infarction and sixty-two healthy control patients were chosen for the analysis of the PAI-1 promoter 4G/5G genotype with polymerase chain reaction-single strand conformation polymorphism. Five myocardial infarction patients and six in the control group were homozygous for the 4G/4G genotype. Twenty-eight and 27 4G/5G and 33 and 29 5G/5G genotypes were found in myocardial infarction and control groups, respectively. The total frequencies of the 4G and 5G alleles were approximately 30% and 70% in both control and myocardial infarction groups. In conclusion, the PAI-1 promoter genotype is not a risk factor for myocardial infarction in the Japanese population. This is in contrast to the first report in Caucasians, suggesting an interaction with other genetic or environmental factors which influences the risk of myocardial infarction.

Aged↗
PubMed1997

B7/BB-1 expression and hepatitis activity in liver tissues of patients with chronic hepatitis C.

Cytotoxic T lymphocytes (CTL) are closely related to the mechanism of liver injury in chronic viral hepatitis. Recently, it has been suggested that antigen-specific T cell activation requires both presentation of antigen by major histocompatibility complex (MHC) molecules and the delivery of costimulatory signals. Such signals are provided by B7/BB-1, one of the most important accessory molecules, sufficient for causing antigen-specific MHC-restricted T cell activation. To evaluate the role of B7/BB-1 in chronic hepatitis C, we immunohistochemically studied its expression in liver tissues obtained from 61 patients with hepatitis C virus (HCV) infection and compared them based on hepatitis activity. In HCV-infected liver, B7/BB-1 was strongly expressed in the cytoplasm of hepatocytes. B7/BB-1-positive cells accompanied liver-infiltrating lymphocytes and were mainly detected in the periportal region. B7/BB-1 expression was closely correlated with the activity of viral hepatitis as evaluated from scores of periportal or intralobular inflammation and necrosis, or serum alanine transferase (ALT) levels. Further study by immunostaining with anti-HCV core and anti-human leukocyte antigen (HLA) class I antibody showed B7/BB-1 positive cells near HCV core antigen- and HLA class I-positive cells, with B7/BB-1-positive cells mostly included among HLA class I-positive cells. These findings suggested that B7/BB-1 expression by hepatocytes may be induced by HCV infection and may trigger generation and activation of CTL, which may cause damage to HCV-infected HLA class I-expressing hepatocytes.

Adult↗
PubMed1997

Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma.

Costimulation mediated by costimulatory molecules, such as B7-1 and B7-2, which are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)-4 counter-receptor, plays an important role in the induction of T cell-mediated antitumor immunity. We investigated the expressions of B7-1, B7-2, and human leukocyte antigen (HLA) class I in seven human hepatocellular carcinoma (HCC) cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. RT-PCR showed that all these human HCC cell lines were positive for B7-1 and B7-2 at the messenger RNA (mRNA) level. Flow cytometric analysis revealed that they all expressed B7-1, B7-2, and HLA class I on the cell surface. However, the expression levels of B7-1 and B7-2 were very low whereas those of HLA class I were high. B7-1 and B7-2 expression could be increased by treatment with interferon alpha and interferon gamma in a dose-dependent manner, although the expression levels of B7-1 and B7-2 after interferon treatment remained low. By transfecting Hep3B cells with a plasmid containing human B7-1 complementary cDNA (cDNA), we were able to establish Hep3B cell lines strongly expressing B7-1. From mixed lymphocytes and tumor cultures analysis, the primary cytolytic activity against parental Hep3B cells could be induced effectively by B71-transfected Hep3B cells. These findings suggested that B7-1 gene transfer is the best way to induce strong expression of this molecule and this might be useful for immuno-gene therapy against human HCC.

Antigens, CD↗
PubMed1997

Interleukin-6 overexpression cannot generate serious disorders in severe combined immunodeficiency mice.

C57BL/6 human interleukin-6 (IL-6) transgenic mice develop mesangial proliferative glomerulonephritis with massive IgG1 plasmacytosis and die of renal failure in early life. To test whether the IL-6 overexpression could cause development of mesangial proliferative glomerulonephritis without plasmacytosis or promote proliferation of immature B cells that have not undergone immunoglobulin gene rearrangement, the IL-6 transgene was introduced into mice with severe combined immunodeficiency (SCID). In the immunocompetent littermate IL-6 transgenic mice, there were various symptoms such as plasmacytosis, nephropathy, anemia, and thrombocytosis, accompanied by marked increases in serum IL-6 levels as they aged. All these mice died by 25 weeks of age. In contrast, the SCID-IL-6 transgenic mice had no such abnormalities, except certain hematological changes, although the transgene was expressed in various tissues. In these mice, the serum IL-6 levels were 10- to 15-fold higher than those in the nontransgenic mice, and they remained constant throughout their lives. Furthermore, there were no signs of lymphoid development. This study demonstrates that deregulation of IL-6 expression does not stimulate cell growth or differentiation of immature B cells, and thus does not result in plasmacytosis and age-related increases in IL-6 production, and also does not generate mesangial proliferative glomerulonephritis.

Animals↗
PubMed1997

Myocardial stretch induced by increased left ventricular diastolic pressure preconditions isolated perfused hearts of normotensive and spontaneously hypertensive rats.

OBJECTIVE: The aim of our study was to determine whether myocardial stretch (non-ischemic stress) could precondition isolated perfused hearts of both normotensive Wister-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: The perfused hearts in Langendorff mode were subjected to 30 min of global no-flow ischemia followed by 30 min of reperfusion. Left ventricular developed pressure (LVDP) and end-diastolic pressure (LVEDP) were measured. In the control group, LVEDP was set at 10 mmHg. In the stretch group, LVEDP was increased to 30 or 60 mmHg for 5 min before 30 min of ischemia. In the ischemic preconditioning group, the hearts were exposed to two cycles of a 5-min period of ischemia before 30 min of ischemia. Myocardial lactate contents were measured at the baseline and at the end of the 60 mmHg stretch. RESULTS: Hemodynamic parameters of LVDP and LVEDP at 30 min of reperfusion improved in the stretch group (LVEDP of 60 mmHg) and the ischemic preconditioning group. Coronary flow did not decrease during the stretch. Recovery of the coronary flow during reperfusion was better in the stretch and ischemic preconditioning groups. Postischemic contractile function was better in WKY rats than in SHR. Myocardial lactate contents at the end of 60 mmHg stretch were negligible. CONCLUSIONS: Myocardial stretch induced by increasing LVEDP preconditioned isolated perfused hearts of both WKY rats and SHR, via mechanisms not involving myocardial ischemia during stretch.

Animals↗
PubMed1997

Overexpression of PRAD1/cyclin D1 in plasma cell leukemia with t(11;14)(q13;q32).

Two patients with plasma cell leukemia (PCL) with a t(11;14)(q13;q32) translocation are reported. Case 1 is a 64-year-old woman diagnosed as having primary PCL (IgA/lambda, Stage III) with high serum LDH and beta 2-microglobulin (beta 2MG) levels. She was treated with combination chemotherapy but died of gastrointestinal bleeding on the 45th hospital day. Case 2 is a 52-year-old man, initially diagnosed with multiple myeloma (IgG/kappa, Stage III) in August 1993. Relapse several months after primary chemotherapy was characterized by a rapid increase in plasma cells in peripheral blood, high serum LDH and beta 2MG levels, and resistance to further chemotherapy. Both cases showed complex karyotypic abnormalities including t(11;14), and Northern analysis revealed overexpression of the PRAD1/ cyclin D1 gene. The PRAD1 gene is found on chromosome band 11q13 and encodes cyclin D1. Cyclin D1 plays an important role in control of the cell cycle, and overexpression of PRAD1/cyclin D1 may be involved in disease progression in these cases.

Chromosomes, Human, Pair 11↗
PubMed1997

Neutralization of transforming growth factor beta 1 augments hepatitis C virus-specific cytotoxic T lymphocyte induction in vitro.

In hepatitis C virus (HCV) infection, TGF-beta 1 is upregulated in the liver and may be involved in the pathogenesis of chronic liver disease. TGF-beta 1 is also produced by activated T cells and acts as a potent immunosuppressor. The aim of this study was to investigate the roles of TGF-beta 1 in HCV-specific cytotoxic T lymphocyte (CTL) induction and enhance their killer activity by TGF-beta 1 modulation. We generated anti-HCV CTL from peripheral blood mononuclear cells from HLA-A2 patients under stimulation with the HCV-core peptide having the HLA-A2.1 binding motif. The lytic activities of CTL or precursor frequency (CTLpf) generated with or without anti-TGF-beta antibody were compared. To optimize the IL-2 dose for CTL induction, low (50 U/ml) and high (500 U/ml) doses were tested and the lytic activities were compared. TGF-beta 1 amounts in the supernatants were assessed by enzyme-linked immunosorbent assay and by their growth inhibitory effect on mink lung epithelial cells. CTL activity was enhanced by anti-TGF-beta antibody in a dose-dependent manner but CTLpf did not significantly change. A high dose of IL-2 reduced the activity to 45% of that observed with a low dose, whereas TGF-beta 1 increased as the dose of IL-2 increased. Exogenous IL-10 reversed the inhibitory effect of a high dose of IL-2 on the killing activity by reducing TGF-beta 1 mRNA expression in T cells and its production. These results demonstrated that endogenous TGF-beta 1 is an autocrine suppressor in CTL induction in vitro. Therefore, the blockade of endogenous TGF-beta 1 could enhance the killing potential of anti-HCV CTL.

Adult↗
PubMed1997

[Effect of aprotinin on bleeding during and graft patency after coronary artery bypass grafting].

The purpose of this study was to evaluate the effect of aprotinin on intraoperative bleeding and graft patency in 200 patients undergoing elective CABG. Patients were classified into three groups; patients receiving 1500000 KIU of aprotinin (group A), 300000 KIU of aprotinin (group B) and no aprotinin as the control (group C). The groups were almost the same as to age, sex, number of grafts and use of ITA. Intraoperative bleeding and reexploration were significantly decreased in group A compared with group B and C. All patients underwent coronary angiography between the 4th and 8th post-operative weeks. Graft patency was significantly decreased in group A (SVG: 90.4%, ITA: 91.1%) compared with group B (SVG: 95.3%, ITA: 100%) and C (SVG: 95.5%, ITA: 99.2%). Perioperative myocardial infarction increased in group A (3.7%). Aprotinin was effective in reducing intraoperative bleeding in CABG, but decreased early graft patency after CABG. It is suggested that aprotinin should not be used routinely in CABG unless a patient has bleeding tendency which is likely to be seen in emergency and redo surgery.

Aged↗
PubMed1997

[Usefulness of 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT in a congestive heart failure patient with isolated coronary ostial stenosis].

We reported a 47-year-old female with congestive heart failure (CHF) of unknown origin. In this case, it was suggested that 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT images were useful in the diagnosis of CHF of unknown origin. She had complained of easy fatigability and dyspnea on effort since Sep. 1995. She was admitted to our hospital because of worsening of symptoms in Dec. 1995. Slightly decreased uptake in anterior, lateral and apical walls was recognized in 99mTc-tetrofosmin SPECT images, meanwhile 123I-BMIPP SPECT images showed markedly reduced uptake in the same areas. This discordance in the distribution between 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT suggested that CHF was not due to dilated cardiomyopathy, but ischemic myocardial disease. Coronary angiography revealed 90% stenosis at the just proximal of left coronary artery. This case was diagnosed an isolated coronary ostial stenosis with CHF, because she was menstruated middle aged woman and did not have a history of aortitis syndrome, syphilis and coronary risk factor before.

Coronary Disease↗