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Biomedical subjects

H Tsubouchi

Publications and source records attributed to H Tsubouchi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Enhanced engraftment of HTLV-I-infected human T cells in severe combined immunodeficiency mice by anti-asialo GM-1 antibody treatment.

The effects of anti-asialo GM-1 antibody (AAGM) treatment on the engraftment of human T-cell leukemia virus type I (HTLV-I)-infected human T cells in severe combined immunodeficiency (SCID) mice were studied. The frequency of tumor formation in an HTLV-I-transformed human T-cell line, MT-2 cells, at the site of inoculation was significantly higher in AAGM-treated than untreated mice (P<0.05): 16/18 (89%) and 16/26 (62%), respectively. The promotive effect of AAGM treatment on tumor development was marked in the early stage (less than 3 weeks), suggesting that the immediate reaction of natural killers to the inoculated cells may be important for the prevention of tumor development. The surface phenotypes and clonality of the tumor cells were the same as the MT-2 cells inoculated. Inoculation of peripheral blood mononuclear cells (PBMC) from one of the 4 adult T-cell leukemia/lymphoma (ATL) patients resulted in the development of tumors in AAGM-treated SCID mice. However, the surface phenotypes of the cells from these tumors were a mixture of B cells and T cells, suggesting that these tumors consisted of Epstein-Barr virus-transformed B cells and HTLV-I-transformed T cells. In addition, HTLV-I was detected by polymerase chain reaction in various organs of the mice inoculated with PBMC from the ATL patient and the asymptomatic carrier examined. These results suggest that elimination of natural killer function by AAGM treatment is important, although such treatment is not always necessary for the engraftment of HTLV-I-infected cells in SCID mice.

Animals↗
PubMed1996

Multiple endocrine neoplasia type 1 associated with malignant lymphoma and other complications.

A 49-year-old female with multiple endocrine neoplasia (MEN) type 1 associated with malignant lymphoma, lipoma, functioning adenomatous goiter, non-functioning adrenal tumor, polyneuropathy, postoperative primary hyperparathyroidism, and hepatitis B virus was a human T lymphotropic virus type 1 (HTLV-1) carrier. She underwent parathyroidectomy for primary hyperparathyroidism at age 44. At age 49, examinations of the enlarged para-aortic lymph nodes revealed diffuse small non-cleaved B cell lymphoma in stage II, and other various complications were also found. Multiple tumorigenetic factors were considered to be involved in the present case.

Adrenal Gland Neoplasms↗
PubMed1996

Genotypic identification of Rickettsia tsutsugamushi by restriction fragment length polymorphism analysis of DNA amplified by the polymerase chain reaction.

We combined the nested polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for genotypic identification of Rickettsia tsutsugamushi. Four primers were selected from the DNA sequence of the gene encoding a 56-kD serotype-specific antigen of the Karp strain. Nested PCR produced rickettsia-specific products of approximately 0.6 kb in the amplification of DNA prepared from three reference strains (Gilliam, Karp, and Kato) and two prototype strains (Irie and Hirano) prevalent in the Miyazaki Prefecture of Japan. When the nested PCR products obtained from these five strains were digested with Hha I, profiles specific to each strain were generated. Fourteen of 17 DNA samples of peripheral blood mononuclear cells from patients with scrub typhus tested positive in the nested-PCR, providing a rickettsia-specific band. The serotype of infected rickettsia of 10 patients were diagnosed as Irie and those of four patients were diagnosed as Hirano by indirect immunofluorescence methods. The fragment profiles of the PCR products of these 14 patients after digestion with Hha I corresponded closely with those serotypes. However, the PCR products from two of four samples, which were similar to Hirano strain by a serologic method and by the pattern of digestion with Hha I, produced different RFLP profiles upon further digestion with Hinf I and Alu I. These results may suggest that genetic variation exists within serotypes. Genotypic identification of R. tsutsugamushi by means of PCR-RFLP using three restriction enzymes is apparently useful.

Adult↗
PubMed1996

Retinal complications during interferon therapy for chronic hepatitis C.

OBJECTIVES: Various side effects of interferon (IFN) therapy have been reported. In this study, we examined retinal change during IFN therapy. METHODS: We performed ophthalmological examinations before, during, and after therapy on 63 patients with chronic hepatitis C who were receiving either natural IFA-alpha or recombinant IFN-alpha 2a or 2b. RESULTS: No retinal lesion was detected before IFN therapy, but, during therapy, retinal abnormality or retinopathy developed in 36 (57.1%) of 63 patients, including retinal hemorrhage in 25 patients and cotton-wool spots in 28 patients. They were noted early in the course of IFN therapy, within the first 4 wk in 67% (24/36) and within 8 wk in 86% (31/36). The incidence was not influenced by the type of IFN but was higher among diabetic (11/12, 92%, p < 0.05) or hypertensive patients (4/5, 80%, not significant) than among patients without either diabetes or hypertension (24/49, 49%). There was no relation between the incidence of retinopathy and the level of ALT activity or white blood cell or platelet counts. However, retinopathy occurred in most patients receiving IFN therapy after white blood cell count and platelet count reached a nadir. The levels of LDL-cholesterol and the atherosclerotic index in patients with retinopathy were slightly higher than those in the patients without retinopathy. CONCLUSIONS: These results suggest that retinopathy often occurs in patients with chronic hepatitis C who are receiving IFN and that we should closely monitor patients for retinal complications during IFN therapy.

Adult↗
PubMed1996

Core promoter mutations of hepatitis B virus for the response to interferon in e antigen-positive chronic hepatitis B.

OBJECTIVES: Mutations in the precore region are not always detected in hepatitis B virus (HBV) from patients with chronic hepatitis B who respond to interferon and lose hepatitis B e antigen (HBeAg) from serum. The other mutations may also be responsible for the loss of HBeAg and response. METHODS: Forty six consecutive patients with HBeAg-positive chronic hepatitis B received recombinant-alpha 2 a interferon (total dose: 702 MU). The mutation for stop codon 28 in the precore region was determined by restriction fragment length polymorphism, and mutations in the core promoter were searched for in five HBV DNA clones propagated from each patient. RESULTS: HBeAg was cleared at 6 months after interferon in 11 (61%) of 18 patients with the precore mutation and in 12 (43%) of 28 without it. Of these 28 patients, 19 with mutations in the core promoter in all five HBV DNA clones lost HBeAg more frequently than the remaining nine who had at least one clone among the five that lacked such mutations (58 vs 11%, p < 0.05). CONCLUSIONS: HBeAg-positive patients infected with HBV variants having mutations for an HBeAg-negative phenotype would respond better to interferon by clearing HBeAg from serum. Such mutations may not necessarily be in the precore region but also in the core promoter, which would interfere with the synthesis and secretion of HBeAg either at the translation or transcription level.

Adult↗
PubMed1996

[Detection of early esophageal and gastric cancers by mass screening].

The purpose of mass screening is to decrease the mortality rate of diseases which are fatal if advanced by detecting them at an early and curable stage. From this point of view, we describe here the present state of mass screening, its problems, and the future of mass screening for esophageal and gastric cancer in Japan. The conventional X-ray examination commonly used to detect esophageal cancer does not seem to be effective in detecting the malignancy at an early stage. Therefore, endoscopic examination with Lugol staining for high-risk groups is recommended for the purpose. In contrast, mass screening for gastric cancer by X-ray examination, which has been applied until now, has reduced the mortality rate of gastric cancer. At the same time, however, as various problems are pointed out, some additional investigations have been undertaken to further reduce the mortality rate of gastric cancer. As social circumstances change, and therapy as well as diagnosis for the disease improves, it is necessary to evaluate the accuracy, problems, and limits of the present system to conduct effective and functional mass screening program. The present system must be adapted it to reflect improvements and changes.

Adult↗
PubMed1995

Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro.

Three new cell lines of human glioblastoma have been established. These cells co-expressed hepatocyte growth factor (HGF) and its receptor, c-Met, genes in vitro. Reverse-transcriptase/polymerase-chain reaction study revealed that the cells also expressed gene for HGF activator, a recently cloned serine proteinase, suggesting that HGF might have a role in glioma cells in vitro as an autocrine factor. The activator mRNA was also detected in other well-established glioma cell lines, glioma tissues and normal brain. The concomitant expression of HGF, HGF activator and c-met was also detected in one glioblastoma case in vivo out of five tested.

Base Sequence↗
PubMed1995

Synthesis and biological evaluation of a series of new parenteral optically active 3-[[(N-alkylpyridinium-4'-yl)thio]methyl]-2-oxaisocephems.

The preparation and biological evaluation of a series of 7-[2-(2-aminothiazol-4-yl)-2-(Z)-[(cyclopentyloxy)imino]acetamido] optically active 2-oxaisocephems, substituted at the 3-position with [(N-alkylpyridinium-4'-yl)thio]methyl groups, are described. The resulting family of parenteral compounds displays a broad spectrum of in vitro antibacterial activity. These compounds exhibit increased activity against Gram-positive organisms including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis which are resistant to most cephalosporins with a similar level of Gram-negative activity to that of the third-generation antibiotics. In vivo efficacy of new antibacterial agents in this investigation is excellent against both Gram-positive and Gram-negative bacteria as compared with reference compounds. The in vitro and in vivo antimicrobial activity and the structure-activity relationships are presented.

Animals↗
PubMed1995

Synthesis and biological properties of a series of optically active 2-oxaisocephems.

A novel series of (6S, 7S)-3,7-disubstituted-8-oxo-1-aza-4-oxabicyclo[4.2.0]oct-2-ene-2- carboxylic acids 9a-o, parenteral optically active 2-oxaisocephems, was synthesized, and in vitro and in vivo activities were determined against Gram-positive and Gram-negative bacteria. The 7-[2-(2-aminothiazol-4-yl)-2-(Z)-cyclopentyloxyimino]acet arnido derivatives, 9g, 9m and 9o, had enhanced antibacterial activity against Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis while maintaining Gram-negative activity. It is also significant that these compounds showed more potent activity against MRSA and E. faecalis isolates than cefuzonam (10) and flomoxef (12), which are the most popular third-generation antibiotics. The combination of the 7-[2-(aminothiazol-4-yl)-2-(Z)-cyclopentyloxyimino]acetamido group and 2-oxaisocephem nucleus contributes to the increased antibacterial activity against these clinical isolates. The 7-[2-(2-aminothiazol-4-yl)-2-(Z)-cyclopentyloxyimino]acet ami do derivative 9g provided good subcutaneous efficacy and exhibited more potent activity than cefmenoxime (11) against the systemic infection with S. aureus Smith in mice. The compound 9a with a [2-(2-aminothiazol-4-yl)-2-(Z)-methoxyimino]acetamido group at the 7-position showed high in vivo efficacy on the experimental infection caused by Escherichia coli No. 29 in mice.

Animals↗
PubMed1995

Molecular cloning and characterization of a cDNA for the alpha subunit of a G protein from rice.

We report the isolation of a cDNA for the alpha subunit of a G protein from rice (Oryza sativa L. cv. Nipponbare). The cDNA contained an open reading frame that encoded a protein of 380 amino acid residues with a mol wt of 44,204. We designated this polypeptide RGA1 (rice G protein alpha subunit 1). The amino acid sequence of RGA1 was 77% and 86% identical to the sequences of alpha subunits from Arabidopsis thaliana and tomato (products of GPA1 and TGA1), respectively, and 42% to 69% identical to sequences of mammalian alpha subunits. The regions essential for binding to GTP were preserved throughout all alpha subunits from higher plants and mammals. However, the C-terminal amino acid sequence, which has been proposed to be a receptor-binding region, of RGA1 was different not only from the analogous sequences of mammalian alpha subunits but also from those of the products of GPA1 and TGA1. The mRNA for RGA1, of 1.7 kb in length, was found in the roots and in the etiolated and greening leaves of rice, suggesting that RGA1 might be a protein that is expressed constitutively.

Amino Acid Sequence↗
PubMed1995

Increased prevalence of HTLV-I infection in patients with hepatocellular carcinoma associated with hepatitis C virus.

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co-infection with the human T-lymphotropic virus type I (HTLV-I) might be associated with this transition in a cross-sectional analysis of 127 patients with HCV-chronic hepatitis (mean age = 51.7) and 43 patients with HCV-associated HCC (mean age = 62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) (P = 0.001). The relative risk (RR) of association was 12.8 (P = 0.0004) among the males, however, no association was evident among the females, RR = 1.3 (P = 0.80). The increased prevalence of HTLV-I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co-infection with HTLV-I may contribute to the development of HCC among patients with HCV-induced chronic liver diseases in a highly HTLV-I-endemic area.

Adolescent↗
PubMed1995

Interferon-alpha 2a for chronic hepatitis B with e antigen or antibody:comparable antiviral effects on wild-type virus and precore mutant.

Recombinant interferon-alpha 2a (IFN-alpha 2a) in a total dose of 702 MU was given to 31 patients: nine with wild-type hepatitis B virus (HBV) and hepatitis B e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild-type HB and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA was ultimately lost in four patients in group C, as well as in 10 patients in group D. Thus, patients with HBeAb and infected with precore mutants alone (D) lost serum HBV DNA more often than those with HBeAg and wild-type HBV (A). Patients with low pretreatment levels of HBV DNA cleared virus more frequently, and the response of precore mutant to IFN was comparable with that of wild-type HBV in patients who had a mixed infection. Based on these results, precore mutants do respond to IFN, and therefore, IFN is indicated in patients with HBeAb, especially those with low serum HBV DNA levels.

Adult↗
PubMed1995

Observation of T cell surface antigens in the clinical course of adult T-cell leukemia: case report of a spontaneous remission.

A patient with acute adult T-cell leukemia (ATL) in whom spontaneous remission was observed without any specific treatment having been given is described. The abnormal cell phenotype was CD4+, CD45RO+ and CD8-. As the number of abnormal cells decreased, CD4+ cell count decreased and CD8+ cells and CD45RA+ cells increased to normal levels (45 and 77%, respectively). Further, the number of cells with CD45RO antigen of intermediate fluorescence intensity increased. Five months after admission, we assessed the patient as being in a state of complete clinical remission; no abnormal cells were detected in peripheral blood, lymph node enlargement had disappeared and the serum chemistry was normal. When the abnormal cells in peripheral blood had disappeared, Southern blot analysis for HTLV-I proviral DNA still revealed a weak monoclonal band with EcoRI digestion, and HTLV-I proviral DNA was detected by polymerase chain reaction analysis. Thus, it appeared that very few abnormal cells persisted although the laboratory findings for ATL were normal. Our case could contribute to the understanding of the mechanism that underlies spontaneous remission in ATL.

Adult↗
PubMed1995

Synthesis and antibacterial activities of optically active substituted 1,2-dihydro-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids.

A series of optically active substituted 1,2-dihydro-6-oxo-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids was prepared via optically active 2-methyl-4,5-difluoroindoline (10) and tested for antibacterial activities. Among them, (2S)-9-[(3R,1'S)-3-(1'-amino)ethyl-1-pyrrolidinyl]-8-fluoro-1,2-dihydro- 2- methyl-6-oxo-6H-pyrrolo[3,2,1-ij]-quinoline-5-carboxylic acid (19) showed potent activity against gram-positive bacteria and (2S)-8-fluoro-1,2-dihydro-2-methyl-9-(3-methyl-1-piperazinyl)-6-oxo-6H- pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid (16) exhibited well balanced in vitro activity, good intravenous efficacy, and high aqueous solubility.

Anti-Bacterial Agents↗
PubMed1995

Eradication of Rickettsia tsutsugamushi from patients' blood by chemotherapy, as assessed by the polymerase chain reaction.

The presence of Rickettsia tsutsugamushi DNA in peripheral blood mononuclear cells of eight patients with tsutsugamushi disease was determined by the polymerase chain reaction during antibiotic treatment with minocycline or doxycycline. Rickettsia tsutsugamushi DNA was detectable in all samples from these patients collected the day before treatment began. After the initiation of chemotherapy, all samples tested positive on the third or fourth day, and one sample tested positive on the eighth day, showing a slow action of the drugs against the rickettsia within cells. Immune responses against R. tsutsugamushi also seemed to be important for eradication of the pathogens, as suggested by patients' high antibody titers.

Aged↗
PubMed1995

Evidence for the presence of an inactive precursor of human hepatocyte growth factor in plasma and sera of patients with liver diseases.

Human hepatocyte growth factor (hHGF), which is now known to be the same protein as the scatter factor and the tumor cytotoxic factor, is a heterodimeric protein with one heavy chain and one light chain linked together by a disulfide bond, and is thought to be involved in liver regeneration. Using an enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, we found that a significant amount of single chain precursor of hHGF (pro-hHGF) was present in plasma of patients with fulminant hepatic failure (FHF) and that normal human serum contained a protease or proteases that convert pro-HGF to a heterodimeric (mature) form of hHGF. We also showed that the processing protease activity for hHGF was suppressed by such serine protease inhibitors as leupeptin, antipain, and aprotinin, and that sera of patients with liver diseases such as fulminant hepatic failure, acute hepatitis, chronic hepatitis, and cirrhosis contained not only pro-hHGF but also the protease. This is the first report showing the presence of pro-hHGF in human blood, and our observations suggest that hHGF is synthesized and secreted from the hHGF-producing cells as an inactive pro-hHGF after hepatic injuries, and the pro-hHGF is then converted to an active heterodimeric form of hHGF in the blood. It is also suggested that plasma of patients with liver diseases contains an active protease or proteases that convert pro-hHGF to a mature form of hHGF.

Animals↗