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T Kato

Publications and source records attributed to T Kato.

At least 505 records · Page 28Linked to original sources
PubMed2000

A question and answer E-mail system for responding to query from the general public with which the system manager can identify delayed replies.

We constructed a question and answer system for direct delivery of E-mail queries from the general public to the proper hospital representative and with which the system administrator can monitor E-mail replies. The system consists of two sub-systems; one is an E-mail questionnaire sub-system that automatically delivers E-mail queries to the proper person and an E-mail reply monitor sub-system with which the system administrator can monitor the E-mail replies. The monitor system compares the origin address of the E-mail reply and the destination address on a questionnaire filled out at the time the query is made. In a test of the system, 56 queries were received in 31 days, with 37 replied to. The interval from receipt of an E-mail query to reply was calculated. Nineteen replies were submitted within 2 days.

Administrative Personnel↗
PubMed2000

Sisters homozygous for the spinocerebellar ataxia type 6 (SCA6)/CACNA1A gene associated with different clinical phenotypes.

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease caused by a CAG repeat expansion in the CACNA1A gene. The neurodegeneration that occurs in CAG repeat diseases is considered to share a common mechanism that may result in the gain of a toxic function related to the expanded polyglutamine tracts. However, the phenotypic expression in homozygotes for CAG repeat diseases has been controversial, and is not clearly related to a gain of functional mechanism. We identified a Japanese family with two sisters who were homozygous for the SCA6 with identical CAG repeat expansion (25/25). They showed an earlier age of onset (27 years in both) than their father (44 years), a heterozygote with an expanded allele showing the same CAG repeat length as the homozygotes (25/14). Interestingly, the two sisters showed differences in disease progression and severity, although the age of onset and CAG repeat length were identical. These findings strongly suggest that the gene dosage influences the age of onset, but other unknown factors are also important in the phenotypic expression of homozygous SCA6.

Adult↗
PubMed2000

Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and bacterial heat shock proteins.

Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and heat shock proteins were studied by using enzyme-linked immunosorbent assay to examine levels of immunoglobulin G (IgG) against Escherichia coli GroEL, a recombinant DnaJ of Actinobacillus actinomycetemcomitans heat shock protein, a synthetic peptide made from the 180th to the 188th amino acids of Mycobacterium bovis BCG Hsp65, and a recombinant human Hsp60, in sera obtained from 43 pustulosis palmaris et plantaris patients judged to have chronic infectious diseases of the oral cavity. We found that the titers of IgG against E. coli GroEL and A. actinomycetemcomitans DnaJ in the sera from pustulosis palmaris et plantaris patients were significantly higher than those in the control group, whereas the titers of IgG against the synthetic M. bovis Hsp65 and the recombinant Hsp60 did not differ significantly. Periodontal therapy and extraction of teeth with periapical infectious resulted in remission of pustulosis palmaris et plantaris and a statistically significant reduction in the levels of IgG against E. coli GroEL in 9 of the 22 patients (41%) examined. We also found that the IgG levels against A. actinomycetemcomitans DnaJ in 6 serum samples of 16 (37%) were reduced, but not significantly, after the treatment. These results suggest that the IgG responses to heat shock proteins partially induced by oral bacteria may be related to the onset of pustulosis palmaris et plantaris in some patients.

Adult↗
PubMed2000

Histatin 5 inhibits inflammatory cytokine induction from human gingival fibroblasts by Porphyromonas gingivalis.

Porphyromonas gingivalis is a gram-negative rod associated with the progression of human periodontal disease. It has been demonstrated that outer-membrane proteins as well as lipopolysaccharides from P. gingivalis ATCC 53977 can induce interleukin 6 (IL-6) and IL-8 from the cells of the periodontium in vitro. But, they cannot induce IL-1 and tumor necrosis factor-alpha from the cells. In the present study, we studied the effects of salivary protein on cytokine induction from human gingival fibroblasts by P. gingivalis outer-membrane protein. Histatin 5 suppressed the IL-6 and IL-8 induction by P. gingivalis outer-membrane protein. This activity was more effective when outer-membrane protein was incubated with histatin 5 before addition to the cell culture. The present study indicates that histatin 5 restrains induction of inflammatory cytokines by periodontal pathogens and that histatin is one of the salivary proteins responsible for this activity.

Bacterial Outer Membrane Proteins↗
PubMed2000

Graft failure secondary to necrotizing enterocolitis in multi-visceral transplantation recipients: two case reports.

We report on two recipients of multi-visceral grafts who exhibited sudden onset of acute abdomen discomfort 2 weeks post-transplantation after a fairly uneventful immediate post-operative course. Both patients were shown to have pneumatosis intestinalis and one had air in the portal vein. Both patients underwent exploration, which showed non-viable intestine (terminal ileum and colon in the first patient and the entire small intestine distal to the ligament of Treitz in the second patient). There was no vascular thrombosis. The necrotic intestine was resected in both cases. The first patient developed sepsis and died 15 days later despite the rescue efforts. The second patient was re-transplanted twice and is doing well. The histopathology of the segments involved revealed cryptitis, vasculitis, and features of transmural necrosis. Accordingly, both clinical and pathologic features are diagnostic of necrotizing enterocolitis. To our knowledge this is the first report of this complication following intestinal or multi-visceral transplantation.

Adolescent↗
PubMed2000

Mitochondrial dysfunction in bipolar disorder.

Mitochondrial dysfunction is implicated in bipolar disorder based on the following lines of evidence: 1) Abnormal brain energy metabolism measured by 31P-magnetic resonance spectroscopy, that is, decreased intracellular pH, decreased phosphocreatine (PCr), and enhanced response of PCr to photic stimulation. 2) Possible role of maternal inheritance in the transmission of bipolar disorder. 3) Increased levels of the 4977-bp deletion in mitochondrial DNA (mtDNA) in autopsied brains. 4) Comorbidity of affective disorders in certain types of mitochondrial disorders, such as autosomal inherited chronic progressive external ophthalmoplegia and mitochondrial diabetes mellitus with the 3243 mutation. Based on these findings, we searched for mtDNA mutations/ polymorphisms associated with bipolar disorder and found that 5178C and 10398A polymorphisms in mtDNA were risk factors for bipolar disorder. The 5178C genotype was associated with lower brain intracellular pH. mtDNA variations may play a part in the pathophysiology of bipolar disorder through alteration of intracellular calcium signaling systems. The mitochondrial dysfunction hypothesis, which comprehensively accounts for the pathophysiology of bipolar disorder, is proposed.

Adenosine Triphosphate↗
PubMed2000

Continuous infusion of prostaglandin E1 via the superior mesenteric artery can prevent hepatic injury in hepatic artery interruption through passive portal oxygenation.

AIMS/BACKGROUND: Hepatic artery interruption (HAI) causes severe ischemic liver damage, especially following hepatopancreatobiliary surgery. In order to inhibit a decrease in oxygen delivery after HAI, continuous infusion of PGE1 via the superior mesenteric artery (SMA) was administered in pigs and changes in hepatic blood flow and oxygen delivery were investigated. Furthermore, its effectiveness in the prevention of liver injury was evaluated by histology and serum enzyme levels. METHODS: Animals were subjected to HAI without PGE1 infusion (control group n=6) and to continuous infusion of PGE1 (0.02 microg/kg/min) into the SMA (PGE1 group n=6). RESULTS AND CONCLUSION: PGE1 infusion via the SMA not only increased the portal blood flow but also elevated the oxygen content of the portal blood. The reduction in oxygen delivery to the liver was 50% in the control group, and only 13% in the PGE1 group. Serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels 24 h after HAI in the control group were 3415+/-1283 IU/L and 9839+/-2959 respectively while in the PGE1 group they were 939+/-426 IU/L and 5510+/-1545 IU/L respectively. Histological examination showed massive necrosis in the control group at 72 h but only focal liver cell necrosis in the PGE1 group. Based on this finding and the fact that this treatment can be performed easily and safely, continuous infusion of PGE1 via the SMA may be a useful intervention to prevent severe liver damage after hepatic artery interruption.

Alprostadil↗
PubMed2000

AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1.

The Wnt signaling pathway is essential for development and organogenesis. Wnt signaling stabilizes beta-catenin, which accumulates in the cytoplasm, binds to 1-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes. Mutations in CTNNB1 (encoding beta-catenin) or APC (adenomatous polyposis coli) have been reported in human neoplasms including colon cancers and hepatocellular carcinomas (HCCs). Because HCC5 tend to show accumulation of beta-catenin more often than mutations in CTNNB1, we looked for mutations in AXIN1, encoding a key factor for Wnt signaling, in 6 HCC cell lines and 100 primary HCC5. Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs. In cell lines containing mutations in either gene, we observed increased DNA binding of TCF associated with beta-catenin in nuclei. Adenovirus mediated gene transfer of wild-type AXINI induced apoptosis in hepatocellular and colorectal cancer cells that had accumulated beta-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Nifedipine suppresses neointimal thickening by its inhibitory effect on vascular smooth muscle cell growth via a MEK-ERK pathway coupling with Pyk2.

The aim of this study was to determine whether nifedipine could suppress an atherogenic process such as balloon-injured intimal thickening in vivo and the proliferation of vascular smooth muscle cells (VSMC) in vitro. First, we examined the in vivo effect of nifedipine to determine whether it could suppress intimal thickening induced by balloon catheterization. Sprague-Dawley (SD) rats were divided into three groups (L, nifedipine 0.3 mg kg(-1) day(-1); H, nifedipine 3 mg kg(-1) day(-1); C, no nifedipine), and Alzet((R)) osmotic pumps were implanted in their backs for continuous administration. The neointimal layers were completely occupied by proliferated VSMC, and the area ratios of neointima/media treated with nifedipine significantly decreased dose-dependently compared to those of the control. Neither blood pressure nor lipid levels changed among the three groups. We next evaluated the in vitro effect of nifedipine on the proliferation of cultured rat VSMC. Nifedipine decreased the values of [(3)H]-thymidine incorporation and total cellular protein content as well as the levels of phosphorylated extracellular signal-regulated protein kinase (ERK) 1/2, mitogen-activated protein kinase kinase (MEK) 1/2, and even the phosphorylation of Pyk2, in dose-dependent fashions. In addition, nifedipine suppressed the levels of proliferative cell nuclear antigen (PCNA) dose-dependently in both VSMC and balloon-injured thoracic aortae. These results indicate that nifedipine has an inhibitory effect on intimal thickening by attenuating intimal VSMC proliferation, suggesting that nifedipine could be effective for preventing the progression of atherosclerotic plaque as in restenosis after angioplasty.

Actins↗
PubMed2000

Novel gene therapy for rheumatoid arthritis by FADD gene transfer: induction of apoptosis of rheumatoid synoviocytes but not chondrocytes.

Synovial cells in the rheumatoid synovium show abnormal proliferation, leading to joint destruction. Rheumatoid synovial cells express functional Fas antigen and are susceptible to Fas-mediated apoptosis. We have proposed the induction of apoptosis by Fas/Fas ligand system of proliferative rheumatoid synovium as a novel therapy for rheumatoid arthritis (RA). We have recently reported that Fas-associated death domain protein (FADD) plays a key role in Fas-mediated apoptosis of synovial cells in patients with RA. In this study, we determined whether FADD gene transfer could induce apoptosis of RA synoviocytes in vitro and in vivo. Transfection of FADD gene by adenoviral vector into cultured RA synoviocytes induced up-regulation of FADD expression and apoptosis. In addition, local injection of FADD adenovirus (Ad-FADD) eliminated synoviocytes in vivo by induction of apoptosis of proliferating human rheumatoid synovium engrafted in severe combined immunodeficiency mouse, which is the most suitable animal model of RA for the evaluation of treatment strategy in vivo. In addition, Ad-FADD-induced apoptosis was limited to cells of the synovium tissue and did not affect chondrocytes. Our results strongly suggest that FADD gene transfer can induce apoptosis of RA synoviocytes both in vitro and in vivo, suggesting that FADD gene transfer might be effective in the treatment of RA.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Bioassay of bile acids using an enzyme-linked DNA aptamer.

A new analytical method for the detection of bile acids has been developed by adopting an alkaline phosphatase-linked DNA oligomer that binds to bile acids. A 5'-biotin-labeled DNA oligomer with a 40-nucleotide length that is defined by the in vitro selection method was connected with alkaline phosphatase through an avidin-biotin linkage and applied to an enzyme immunoassay format. Sample solutions were incubated with small aliquots for a cholic acid-immobilized agarose matrix, on which the alkaline phosphatase-linked DNA oligomer had been bound prior to carrying out the assay. The amount of the alkaline phosphatase-linked DNA oligomer dissociated from the cholic acid-immobilized agarose matrix, which was detected using a fluorogenic substrate for alkaline phosphatase, indicated the amount of bile acids in the samples. The results suggest that the DNA aptamer directly linked with the reporter enzyme is applicable as a detector ligand for the immunoassay format. A linear calibration range was obtained for cholic acid between 0.1 to 5 mmol l-1 with a limit of detection of 10 mumol l-1. The %RSD was 7 at 5 mmol l-1 of cholic acid.

Animals↗
PubMed2000

Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosis.

BACKGROUND: Proton pump inhibitor triple therapy with clarithromycin and metronidazole has been widely used for Helicobacter pylori eradication. However, the efficacy and the safety of this therapy in patients with liver cirrhosis have not been established. AIM: To evaluate the effect of hepatic dysfunction on metabolism of clarithromycin as it is used for H. pylori eradication therapy in patients with liver cirrhosis, and the efficacy of eradication therapy in those patients. METHODS: Serum levels of clarithromycin and its metabolite. 14-(R)-hydroxyclarithromycin, were examined in 18 subjects (five normal controls and 13 hospitalized patients with liver cirrhosis) on a selected day between days 7 and 10 of a 2-week course of eradication therapy. This therapy consisted of lansoprazole (30 mg, once a day) together with clarithromycin (200 mg, twice a day) and metronidazole (250 mg, twice a day). In addition, 118 H. pylori-positive out-patients, 88 with peptic ulcer and 30 with liver cirrhosis, underwent the same eradication therapy. RESULTS: Values for the area under the 0-6 h concentration-time curve (AUC) for clarithromycin were not significantly different among the groups. However, the AUC (0-6 h) values of 14-(R)-hydroxyclarithromycin were significantly lower in the Child-Pugh C group than in either the normal controls or the Child-Pugh A/B group. The cure rate for the peptic ulcer patients was 84% on a per protocol analysis (95% CI: 80%-88%) and 81% on an intention-to-treat analysis (95% CI: 77%-85%), while in the liver cirrhosis patients it was 89% in a per protocol analysis (95% CI: 78%-99%) and 83% in an intention-to-treat analysis (95% CI: 70%-97%). Mild adverse effects were observed in 10% of the peptic ulcer patients and 13% of the liver cirrhosis patients, with none leading to premature withdrawal from the study. CONCLUSION: The 2-week low-dose lansoprazole-based triple therapy tested is a simple, effective and well-tolerated regimen for H. pylori eradication in patients with liver cirrhosis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Insulin activates p38 mitogen-activated protein (MAP) kinase via a MAP kinase kinase (MKK) 3/MKK 6 pathway in vascular smooth muscle cells.

BACKGROUND: Induction of stress-activated mitogen-activated protein (MAP) kinases such as p38 could be important for the development of cardiovascular diseases since p38 MAP kinase activation stimulates apoptosis, cell growth, prostanoid formation and other cellular dysfunctions when induced by oxidants, hyperosmolarity, or pro-inflammatory cytokines. On the other hand, insulin resistance is one of the most important factors promoting atherogenesis, including cardiovascular diseases, but it is not clear how these different factors transmit their signals intracellularly at the cytosolic and nuclear levels. In this study, we investigated the effect of insulin on p38 mitogen-activated protein (MAP) kinase activation in cultured rat vascular smooth muscle cells (VSMC). MATERIALS AND METHODS: VSMC were obtained from the aortas of male Wistar rats by the media explant technique. After being stimulated by insulin with SB-203580, PD-98059, or GF109203X, the cells were solubilized and the expressions of MAP kinases, MAP kinase kinases and p70 S6 kinase were examined by immunoblot analysis. The amount of DNA synthesis was measured by [3H]thymidine incorporation. RESULTS: Insulin activated p38 MAP kinase phosphorylation in a dose-dependent manner, and the phosphorylation was specifically inhibited by SB-203580, a p38 MAP kinase-specific inhibitor, but not by PD-98059, a specific inhibitor of upstream kinase (MEK), of extracellular signal-regulated kinase (ERK), or GF209203X, a protein kinase C-specific inhibitor. Insulin also activated MAP kinase kinase (MKK) 3/MKK 6 phosphorylation, the upstream kinase of p38 MAP kinase, but neither stress-activated protein kinase (SAPK)/ERK kinase (SEK1/MKK4) nor SAPK/c-jun NH2-terminal protein kinase. Surprisingly, phosphorylation of p70 S6 kinase and an increase of DNA synthesis by insulin were suppressed dose dependently by SB-203580. CONCLUSION: These results have established that insulin activates the p38 MAP kinase cascade via an MKK 3/6 pathway in rat VSMC, independently of a MEK-ERK cascade, and partly regulates cell growth.

Animals↗
PubMed2000

Impaired delayed-type hypersensitivity response in mutant mice secreting soluble CD4 without expression of membrane-bound CD4.

Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell-mediated immunity. We examined the DTH response to methylated bovine serum albumin of a novel mutant strain of mice that have soluble CD4 (sCD4) in their circulation without expression of CD4 on the cell surface. The DTH response of the mutant mice was severely impaired, although the response of CD4 knockout (KO) mice, generated by homologous recombination, was comparable to that of wild-type mice. The response of the mutant mice was restored by the neutralization of sCD4 with anti-CD4, and that of CD4KO mice was markedly reduced by the implantation of a diffusion chamber containing sCD4 cDNA transfectant cells. The restored DTH response of the mutant mice treated with anti-CD4 was abolished by treatment with anti-interferon-gamma (IFN-gamma). IFN-gamma production by CD4 mutant and CD4KO mice was consistent with their DTH response and inversely related to the presence of sCD4 in their circulation, indicating that sCD4 impairs the DTH response by blocking the production of IFN-gamma in our mutant mice. These results raise the possibility that sCD4 could impair cell-mediated immunity. Our mutant mice would provide a useful tool with which to analyse the mechanisms of the DTH reaction.

Animals↗
PubMed2000

Expression of hepatic thrombopoietin mRNA in primary cultured hepatocytes and in rats with acute liver injury or bone marrow suppression with or without cirrhosis.

BACKGROUND AND AIMS: The main causes of thrombocytopenia in cirrhosis are thought to be platelet destruction and the reduction of thrombopoietin (TPO) expression in the liver. The mechanisms by which levels of TPO mRNA are regulated in cirrhosis have not been elucidated. In this study, we investigated some possible mechanisms. METHODS: We used three experimental models: bone marrow suppression, acute liver injury and primary cultured hepatocytes. We used northern blots to assess the kinetics of TPO mRNA expression in the livers of irradiated rats (with and without cirrhosis) in acute liver injury and in primary cultured hepatocytes treated with hepatotoxin or cytokines. RESULTS: Although the bone marrow was hypocellular, there was no apparent enhancement of TPO mRNA expression in the irradiated rats with cirrhotic livers compared with the unirradiated rats with cirrhotic livers. There were no conspicuous changes in hepatic TPO mRNA expression between the livers of the control rats and the three models of acute liver injury. There were no conspicuous changes in the levels of TPO mRNA between control hepatocytes and hepatocytes treated with hepatotoxin or cytokines. CONCLUSIONS: Our results suggest that bone marrow is not a regulator of hepatic TPO production in cirrhosis. The reduced TPO mRNA expression found in cirrhotic rats may not result merely from serious cellular damage; it may be associated with cirrhosis-specific regulatory mechanisms for the expression of the TPO gene. Further studies are needed to search for other factors that may induce reduced TPO expression.

Acute Disease↗
PubMed2000

White matter hyperintensity detected by magnetic resonance imaging and lithium response in bipolar disorder: a preliminary observation.

The possible relationship between deep white matter hyperintensity (WMHI) lesions detected by magnetic resonance imaging and response to lithium was examined in 16 patients with bipolar disorder who had been under maintenance treatment with lithium for more than 1 year. Bipolar patients who had higher scores of WMHI responded significantly better to lithium (r = 0.57, P < 0.05) than did those who had lower scores. This preliminary result suggests that the presence of WMHI may be associated with a better response to lithium.

Adult↗