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Hirohito Tsubouchi

Publications and source records attributed to Hirohito Tsubouchi.

54 records · Page 3Linked to original sources

Serologic assessment of type 1 and type 2 immunity in healthy Japanese adults.

We assessed the informativeness of several serologic biomarkers of immune function using serum specimens collected in the Miyazaki Cohort Study from subjects who were seronegative for anti-human T-cell lymphotrophic virus I and anti-hepatitis C virus. To broadly characterize type 1 immune status, we measured EBV antibody titers, because titer profiles associated with cellular immune suppression are well described. We also tested for three type 2 biomarkers: total serum IgE, soluble CD23, and soluble CD30. Nonreactivity to a tuberculin purified protein derivative (PPD) skin test is indicative of diminished delayed-type hypersensitivity (type 1) responsiveness in the study population due to a history of tuberculosis exposure or Bacillus Calmette-Guérin vaccination. We therefore evaluated the serologic markers as predictors of PPD nonreactivity using logistic regression. Subjects whose EBV antibody profiles were consistent with deficient type 1 immunity were more than thrice as likely to be PPD nonreactive as persons with "normal" antibody titers. Elevated total IgE was also strongly associated with PPD nonreactivity (odds ratio 3.4, 95% confidence interval 1.2-9.9); elevated soluble CD23 had a weaker, but positive, odds ratio, whereas soluble CD30 levels were not predictive of PPD status. Therefore, PPD nonreactivity is associated, in this population, with a pattern of serum biomarkers that is indicative of diminished type 1 and elevated type 2 immunity. We conclude that, with the exception of soluble CD30, the serologic markers are informative for the characterization of type 1/type 2 immune status using archived sera from study populations of healthy adults.

Adult↗

Hepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats.

Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration, serving as a critical regulator of intestinal wound healing. In this study, we examined the effect of administration of recombinant human HGF on colonic mucosal damage in vivo. Acute colitis was induced in rats by feeding with 5% dextran sulfate sodium (DSS) for 7 days, and colitis was subsequently maintained by feeding with 1% DSS. On the 5th day of DSS administration, osmotic pumps releasing recombinant human HGF (200 microg/day) were implanted into the peritoneum of the rats. Continuous intraperitoneal delivery of HGF led to both increased serum human HGF levels and c-Met tyrosine phosphorylation within the colonic mucosa. Compared with mock-treated rats, those administered human HGF showed a reduction in colitis-associated weight loss, large intestinal shortening, and improved colonic erosions. Enhanced epithelial regeneration and cellular proliferation were observed in rats treated with recombinant human HGF. The weights of the liver, kidneys, and spleen were not affected by HGF administration. These results indicate that HGF administration accelerates colonic mucosal repair in rats with DSS-induced colitis and suggest that recombinant human HGF may be a useful therapeutic tool to facilitate intestinal wound healing in patients with ulcerative colitis.

Animals↗

A CRE and the region occupied by a protein induced by growth factors contribute to up-regulation of cyclin D1 expression in hepatocytes.

Induction of cyclin D1 expression is a critical feature of growth factor-induced cell proliferation in hepatocytes. To clarify the mechanisms regulating cyclin D1 gene expression, we isolated the rat cyclin D1 gene and analyzed the transcriptional regulatory elements in rat hepatoma cells and primary cultured rat hepatocytes. Two transcriptional regulatory regions were analyzed. One was mapped to a cAMP-responsive element (CRE) at position -41bp and was occupied by a CRE-binding protein (CREB), resulting in cyclin D1 expression. Another (CD1E0.7), located at -753bp, revealed high homology with binding sites for the Ets family, the hepatocyte nuclear factor-3beta, or the nuclear factor of activated T cells. However, CD1E0.7 did not interact with these nuclear factors and specific interaction with a protein extracted from growth factor-treated rat hepatocytes in primary cultures. These results indicate that CREB binds to the CRE and mediates activation of the cyclin D1 promoter, and suggest that CD1E0.7 may be possibly occupied by a protein induced by growth factors in hepatocytes.

5' Flanking Region↗

Risk factors for the local recurrence of hepatocellular carcinoma after a single session of percutaneous radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electron insertion. METHODS: From February 1999 to September 2001, we treated 104 HCC tumors with an expandable needle with four hooks. Ninety-nine of the 104 tumors were successfully treated by single-session RFA with a single electrode insertion. We investigated the relationships between pretreatment factors (tumor size, tumor staining, tumor capsule, and tumor location) and local recurrence in these 99 tumors. RESULTS: The mean size of the 99 tumors was 21.5 mm in diameter (range, 10 to 33 mm). The overall local recurrence rates were 9.7%, 15.4%, and 20.4%, at 1, 2, and 3 years, respectively. For small tumors (smaller than 25 mm), the local recurrence rates at 1, 2, and 3 years were 4.0%, 8.0%, and 14.6%, respectively. The local recurrence rates were 21.1% and 32.3% at 1 and 2 years, respectively, for large tumors (25 mm or larger), and at 3 years the rate was over 50% for tumors located close to the liver surface. Tumor size and tumor location relative to the liver surface were significantly associated with a higher local recurrence rate. However, other variables tested showed no significant relationship to the local recurrence rate. CONCLUSIONS: This study demonstrated that both tumor size and location relative to the liver surface influence the local efficacy of single-session RFA with a single electrode insertion.Radiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electrode insertion.

Aged↗

Osteoactivin expressed during cirrhosis development in rats fed a choline-deficient, L-amino acid-defined diet, accelerates motility of hepatoma cells.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly cirrhosis. However, the genes involved in hepatocarcinogenesis in the context of developing cirrhosis remain unknown. This study aims to identify genes associated with early cirrhosis-associated hepatocarcinogenesis. METHODS: We examined genes differentially expressed between the livers of normal rats and rats fed a choline-deficient, L-amino acid-defined (CDAA) diet using suppression subtractive hybridization. We examined both the expression in the liver and HCC tissues of osteoactivin (OA), isolated in this screen, and its effect on invasiveness and metastasis. RESULTS: OA mRNA was strongly expressed in the livers of rats fed the CDAA diet for 1-3 months. Moderate expression was sustained for 18 months. OA overexpression increased the invasiveness and metastasis of rat hepatoma cells in vitro and in vivo. In humans, OA expression was not detectable in normal liver tissues. While OA transcripts were detectable in cirrhotic nontumorous liver tissues surrounding HCCs, the majority of HCC tissue samples exhibited higher levels of OA expression than the surrounding normal tissue. CONCLUSIONS: These results indicate that OA is a novel factor involved in the progression of HCC via stimulation of tumor invasiveness and metastatic potential.

Aged↗

Branched-chain amino acids supplements in the late evening decrease the frequency of muscle cramps with advanced hepatic cirrhosis.

Eight outpatients with advanced hepatic cirrhosis were tested over 3 months for branched-chain amino acids (BCAA) supplements in the late evening. Serum albumin level (2.8+/-0.3 vs. 3.1+/-0.2 g/dl, P<0.002), serum cholin esterase activity (54+/-13 vs. 67+/-17 IU/l, P<0.02), and plasma Fischer's ratio (1.3+/-0.9 vs. 1.4+/-0.9, P<0.005) increased over the 3 months. The frequency of muscle cramps decreased (7.4+/-2.0 vs. 0.3+/-0.5 times/week, P<0.0001) dramatically. These data suggest that BCAA supplements in the late evening are of benefit to malnourished patients with hepatic cirrhosis. Relief of muscle cramping is an important outcome of BCAA supplements in the late evening.

Journal Article↗

Bridging use of plasma exchange and continuous hemodiafiltration before living donor liver transplantation in fulminant Wilson's disease.

A 15-year-old girl presented with acute hepatic failure showing ascites and hepatic encephalopathy, accompanied by hemolytic anemia. She was diagnosed as having fulminant Wilson's disease (FWD). Plasma exchange (PE), continuous hemodiafiltration (CHDF) and D-penicillamine administration were started immediately. Copper [24,000 microg] was removed by PE and CHDF over three days, which relieved the jaundice and the consciousness disorder. A successful liver transplant followed. FWD progresses rapidly and often liver transplantation is the only possible therapy. In this case, PE and CHDF were an effective therapy bridge until liver transplantation.

Adolescent↗

Genetic evidence of transmission of human T cell lymphotropic virus type 1 between spouses.

Sexual transmission of human T cell lymphotropic virus type 1 (HTLV-1) is considered to be an important route of infection in adults. However, no direct evidence has been reported that supports this observation. To address this issue, sequence variations of the gp46 (envelope)-coding region of HTLV-1 were determined in 13 patients infected with HTLV-1 who experienced seroconversion and in their spouses. Twenty-two nucleotide changes that were different from the reference sequence of lambdaATK-1 were identified. However, the gp46 sequences found were identical within each married couple. HTLV-1 proviral DNA loads measured in 11 of these couples varied from 10 to 3430 copies per 10(5) PBMC, and the proviral DNA loads of spouses often differed. This study provides the first genetic confirmation of the transmission of HTLV-1 from a carrier spouse to his/her partner. The findings also suggest that host-related factors play a more important role than do virus-specific factors in determining HTLV-1 proviral DNA load.

Base Sequence↗

Rapid phenotypic assay for human immunodeficiency virus type 1 protease using in vitro translation.

A rapid in vitro phenotyping method for human immunodeficiency virus type 1 (HIV-1) protease was developed. In this system, both HIV-1 protease and substrates are prepared using a rabbit reticulocyte based coupled in vitro transcription/translation system. The activity of protease is evaluated by the amount of cleaved substrate measured by ELISA. In this system, wild-type protease derived from strain HXB2 was specifically inhibited in a dose-dependent manner by the protease inhibitors, indinavir and nelfinavir. Three drug-resistant proteases carrying a single mutation, D30N, L90M, and V82F, were analyzed in the absence of the inhibitors. Reflecting their impaired fitness, they exhibited decreased protease activity compared with the wild type. The apparent protease activity was greater for a Gag-Pol substrate encompassing the Gag-protease-reverse transcriptase junctions than for a substrate only covering the Gag region. Using the Gag-Pol substrate as the target, the indinavir-resistant mutant V82F was evaluated further. V82F showed 9-fold resistance to its cognitive protease inhibitor, indinavir; however, it manifested only moderate (2-fold) resistance to a non-cognitive inhibitor, nelfinavir. This simple and rapid method may be useful for phenotyping of drug-resistant HIV-1 protease as well as for screening new inhibitors of HIV-1 protease.

Animals↗

[Mycoplasma pneumonia of identical twin sisters with different clinical courses depending on the treatment].

Mycoplasma pneumoniae (M. pneumoniae) pneumonia is a common disease which usually shows a good prognosis, however, it can develop a very serious state such as respiratory distress syndrome. We experienced 2 cases with M. pneumoniae pneumonia from identical twin sisters. Case 1, who was 22 years-old and was the senior sister of the twin, complained of fever and cough on August 1st, 1999. Her chest radiograph revealed consolidation in the right lung. When she was admitted to our hospital on August 11, she revealed severe hypoxemia and the titer to M. pneumoniae was markedly elevated. She was diagnosed as M. pneumoniae pneumonia with acute respiratory distress syndrome and treated with clarithromycin and methylprednisolone. Although it was necessary for her to be in the intensive care unit for 8 days, her condition gradually improved and was discharged on the 30th of September. Case 2, who was the younger sister of Case 1, complained cough and fever on August 21, 1999. Her chest radiograph showed consolidation in the left lung. She was treated by sparfloxacin because the intrafamilial infection of M. pneumoniae was most likely. The diagnosis was confirmed by the increased antibody-titer to M. pneumoniae later. There have been several reports that hyperimmune reaction may be related with the worse course of M. pneumoniae pnuemonia. However, the clinical courses of twin sisters, who should be very similar in their immune response to the same antigen, were very different from each other. The time of administration of effective antibiotics seemed to be a crucial factor to determine their courses. These results emphasized the importance of early diagnosis of the patients with M. pneumoniae pneumonia and the adequate chemotherapy to prevent developing severe respiratory failure.

Adult↗

Detection of human T-lymphotropic virus type I (HTLV-I) infection during coculture of HTLV-I infected and uninfected cells using inverse long PCR.

OBJECTIVE: Identifying the new integration of human T-lymphotropic virus type I (HTLV-I) proviral genome into initially uninfected cells after cocultivation with HTLV-I infected cells is important for clarifying the process of infection. We examined the usefulness of inverse long polymerase chain reaction (IL-PCR) for this purpose. METHODS: An experimental system using IL-PCR was applied to detect the transmission of HTLV-I between irradiated HTLV-I infected cells (HUT102) and uninfected targed cells (MOLT4, K562) after short-term and long-term coculturing. RESULTS: In every coculture experiment with irradiated HTLV-I infected cells and uninfected cells, the new integration of HTLV-I was easily identified by IL-PCR. Oligoclonal proliferation of HTLV-I-positive cells was shown among MOLT4 cells even 4 months after the cocultivation; however, no evidence of viral replication was observed by indirect immunofluorescence assay or reverse transcription-PCR. We also used IL-PCR to assess the inhibitory effects of azidothymidine, anti-gp46, anti-vascular cell adhesion molecule-1 and anti-heat shock cognate protein 70 (HSC70) monoclonal antibody. Integration of HTLV-I provirus was inhibited in all of these cases except for anti-HSC70. CONCLUSION: This experimental method enabled the detection of cell-to-cell transmission of HTLV-I directly and was useful for studying the mechanisms of cell-associated HTLV-I infection.

Cell Line↗

[ATL (lymphoma type) presented with a mass formation in the heart].

A 50-year-old man was admitted to another hospital with epigastralgia. Malignant lymphoma was suspected because the patient had increased levels of serum LDH and an abnormal Ga scintigraphy finding in his chest. When he was transferred to our hospital, he underwent a right inguinal lymphadenopathy. The laboratory data showed increased levels of serum LDH and soluble IL-2 receptor, but there was no appearance of peripheral abnormal lymphocytes. His chest MRI indicated tumors in the right atrium (4 cm x 4 cm) and in the head of his left humerus. Those tumors were enhanced by Gd-DTPA. There were no other lymphadenopathies. Histopathological and immunohistochemical studies showed T-cell type lymphoma in the right inguinal lymph node. Furthermore, monoclonal rearrangement of HTLV-I proviral DNA was detected from the lymph node by Southern blot analysis. Taken together, we diagnosed the patient as having ATL (lymphoma type). His condition has improved well with systemic chemotherapy. We report a rare case of lymphoma type ATL with initial massive cardiac involvement, although ATL cells sometimes involve the heart at the end of the disease course.

Heart Neoplasms↗