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Biomedical subjects

H Tsubouchi

Publications and source records attributed to H Tsubouchi.

At least 109 records · Page 6Linked to original sources

Altered expression of class I HLA antigen on peripheral mononuclear cells in patients with adult T-cell leukemia: inverse relationship with natural killer susceptibility.

Patients with adult T-cell leukemia showed altered expression of class I HLA antigen in their peripheral blood lymphocytes. Acute type adult T-cell leukemia showed increased levels of the antigen expression compared to those of control group and smoldering type (P < 0.001 and 0.01, respectively). Natural killer sensitivity of infected cell lines with different levels of class I HLA expression showed an inverse relationship with the antigen expression. Further, various cell lines including human T-cell leukemia virus type I-infected cell lines treated with acid buffer, which selectively eliminated the surface class I HLA molecules from cell membrane, became more sensitive to natural killer-mediated lysis. These data suggested that the enhanced expression of class I HLA on peripheral blood lymphocytes of patients with acute type adult T-cell leukemia may contribute to escaping from the immunosurveillance system of natural killer cells in vivo.

Adult↗

[Study on prognostic factors in twenty-five patients with myelodysplastic syndrome].

Twenty-five consecutive patients with myelodysplastic syndrome (MDS) were followed in the Second Department of Internal Medicine, Miyazaki Medical School from 1984 to 1993. The diagnosis of MDS was morphologically based on the criteria of FAB. At the time of diagnosis, 9 patients had refractory anemia (RA), 1 had RA with ring sideroblasts (RARS), 6 had RA with excess blasts (RAEB), 6 had RAEB in transformation (RAEB-t), and 3 had chronic myelomonocytic leukemia (CMMoL). Prognostic factors involved in survival times and progression to leukemia were analyzed in these patients; FAB classification of MDS, age, sex, peripheral blood cell counts, bone marrow examination, karyotype, numbers of blasts. None of these prognostic factors had a significant effect on the prognosis of MDS patients. Study of the therapeutic effects on MDS patients revealed no significant increase of survival time in treated MDS patients compared to non-treated patients. Further, no significant difference in survival time was found between MDS patients treated with or without anticancer drugs. These results indicated that MDS patients were pathologically and therapeutically heterogeneous.

Aged↗

[Acute necrotizing gastritis associated with adult T-cell leukemia in the course of chemotherapy].

A 63-year-old man with smoldering adult T-cell leukemia (ATL) which became acute was admitted. During chemotherapy, he experienced epigastric pain and fever due to neutropenia. The combination therapy of antimicrobials and rhG-CSF was ineffective and he died. Autopsy revealed systemic invasion of ATL cells. The stomach findings resembled those of phlegmonous gastritis, a rare form of bacterial gastritis, along with diffuse, mucosal necrosis with hemorrhage. The pathogenesis of necrotizing gastritis remains to be elucidated. The patient had also received histamine H2 antagonist for gastric ulceration, which might have influenced the gastric bacterial flora.

Aged↗

Immunohistochemistry with antibodies to hepatocyte growth factor and its receptor protein (c-MET) in human brain tissues.

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and also has multifunctional effects on some other cells in various organs. The human c-Met proto-oncogene product has recently been identified as its high-affinity receptor. We examined HGF-like and c-Met protein-like immunoreactivities in the brains of neurologically normal, lacunar stroke and Alzheimer disease (AD) cases. The HGF antibody stained only round cells in the capillaries and astrocytes in the white matter. Positive staining with the antibody to c-Met protein was seen in microglia, predominantly in the white matter. The possibility of interactions between astrocytes and microglia through HGF and its receptor is suggested.

Aged↗

Plasma hepatocyte growth factor and biliprotein levels and outcome in fulminant hepatic failure.

Plasma levels of growth factors may be important in determining the extent of liver regeneration in patients with fulminant hepatic failure and in this study human hepatocyte growth factor and biliprotein (bilirubin covalently bound to albumin) were determined in patients with fulminant hepatic failure, mainly as a result of acetaminophen overdose. Admission values for plasma human hepatocyte growth factor were significantly raised, although with a wide range in acetaminophen-induced fulminant hepatic failure (median 7.4 ng/ml, range 0.45-48.4 ng/ml, n = 34) and in fulminant hepatic failure from other causes (3.8 ng/ml, 1.72-25.1 ng/ml, n = 9) as compared to normal subjects (0.24 ng/ml, 0-0.5 ng/ml, n = 30). Higher plasma human hepatocyte growth factor was observed in patients who died (10.1 ng/ml, 3.8-48.4 ng/ml, n = 19) than in those who survived (4.3 ng/ml, 0.45-25.1 ng/ml, n = 22, p < 0.02), which may reflect lack of hepatic clearance in the former group. The median plasma biliprotein on admission (13.2 mg/l, range 6.3-100.7 mg/l, n = 43) was significantly increased compared to normal subjects (1.3 mg/l, 0-4.1 mg/l, n = 7, p < 0.001) with no difference between patients who survived or died, although when plasma biliprotein results were expressed as a percentage of the total bilirubin, the values were slightly higher in survivors (median 14.4%, range 10.8-40.5%, n = 23) compared to those who died (12.1%, 7.7-20.9%, n = 20, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Synthesis and antibacterial activities of 2-oxaisocephems.

A series of 2-oxaisocephems with a thio-substituted methyl group at the 3-position and a 2-aminothiazol-4-yl moiety at the 7-position was synthesized via benzyl 3-acetyloxymethyl-7-azido-8- oxo-1-aza-4-oxabicyclo[4.2.0]oct-2-ene-2-carboxylate (2), derived from benzyl acetoacetate (1). The new 2-oxaisocephems were tested for antibacterial activities. Among them, the derivatives having a [2-(2-aminothiazol-4-yl)-2- (Z)-cyclopentyloxyimino]acetamido group at the 7-position characteristically showed potent activities against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis as compared with cefuzonam and cefmenoxime, which are third-generation cephalosporins.

Anti-Bacterial Agents↗

Bulky plasmacytoma of the bone with intracranial invasion.

A 56-year-old man with left anterior chest pain showed two well-defined tumors in the left anterior chest wall and left parietal region. A large osteolytic lesion in the parietal bone and several punched-out lesions in the temporal bone were revealed by a skull X-ray examination. He showed monoclonal gammopathy (IgG, kappa type) and Bence Jones proteinuria, but no proliferation of plasma cells was observed in the bone marrow. The tissue specimens from both lesions consisted of abnormal plasma cells, indicating plasmacytoma. Although a bulky intracranial plasmacytoma was present, the patient did not exhibit intracranial hypertensive symptoms, or neurological abnormalities.

Bence Jones Protein↗

A case report of serologically diagnosed pulmonary anisakiasis with pleural effusion and multiple lesions.

The second known human case of pulmonary anisakiasis is reported. A 22-years-old man living in Hyuga City, Miyazaki Prefecture, Japan, developed high fever, respiratory distress, and pleural effusion after consumption of raw fish. Although his total white blood cell count increased to approximately 10,000-20,000/mm3, eosinophilia was not observed. The total IgE level in his serum markedly increased up to 3,599 IU/ml. Since the patient was suspected to have a parasitic disease, immunoserologic tests were carried out. Screening tests using a multiple dot-enzyme-linked immunosorbent assay (ELISA) and an Ouchterlony double-diffusion test showed that his serum and pleural effusion had the strongest reactivity against crude antigen of Anisakis type I larvae, together with weak cross-reactivity against several other nematode antigens. Since extragastrointestinal anisakiasis was strongly suspected, this diagnosis was confirmed by a microplate-ELISA and Western blot analysis using a monoclonal antibody.

Adult↗

Expression of hepatocyte growth factor in normal and carbon tetrachloride-treated monkeys.

We examined hepatocyte growth factor-producing organs in normal and carbon tetrachloride-treated Japanese monkeys, a species more related to human beings than rats, by measuring hepatocyte growth factor protein and hepatocyte growth factor mRNA in various tissues. Hepatocyte growth factor protein and hepatocyte growth factor mRNA levels were determined by use of an enzyme-linked immunosorbent assay for human hepatocyte growth factor and Northern-blot analysis using human hepatocyte growth factor cDNA as a probe, respectively. Although very slight amounts of hepatocyte growth factor protein were found in various organs of normal monkeys, the hepatocyte growth factor protein levels were remarkably increased only in the livers and spleens of carbon tetrachloride-treated monkeys. Hepatocyte growth factor mRNA was distinctly detected in the livers, spleens, lungs, intestinal tracts, adrenal glands and aortas of normal monkeys. After the administration of carbon tetrachloride, the hepatocyte growth factor mRNA levels in the liver, spleen and gastrointestinal tract were markedly increased; the level in the lung was unchanged, differing from the findings in rats; and the levels in adrenal gland and aorta were unaltered. These results indicate that the liver is an important hepatocyte growth factor-producing organ in monkeys during liver regeneration and that hepatocyte growth factor induced in the liver may stimulate hepatocyte proliferation by way of a paracrine mode.

Animals↗

[Psoriasis exacerbated by alpha-interferon therapy in a case of chronic myelogenous leukemia].

A 49-year old male with chronic myelogenous leukemia (CML) and psoriasis was admitted for interferon treatment. He was given 6 MU of human lymphoblastoid interferon (HLBI), a natural alpha-interferon, daily for 1 month followed by 3 MU every other day for 1.5 months and twice a week for 1 month. Because HLBI administration showed no favorable effects on the hematological findings and because of the exacerbated psoriasis of the patient, it was discontinued. Subsequently his psoriasis improved to the initial findings observed at the admission. We reported a case of CML in which psoriasis was exacerbated during interferon therapy.

Humans↗

Ultrastructural location of human hepatocyte growth factor in human liver.

Human hepatocyte growth factor has been purified from the plasma of patients with fulminant liver failure, but where this factor is produced in organs or cells of subjects with liver diseases is unknown. Therefore, we used a monoclonal antibody to human hepatocyte growth factor to stain cells in three normal and 29 diseased liver tissues by immunohistochemical techniques. By light microscopy, the immunostained cells seemed to be polymorphonuclear leukocytes because of their segmented nuclei. Some biliary epithelial cells also were stained. Electron microscopy confirmed that the immunostained cells with segmented nuclei were polymorphonuclear leukocytes and that the stained grains were on the membranes of rough endoplasmic reticulum, around specific or azurophilic granules and in the cell sap. Stained grains in the biliary epithelial cells were found sporadically on the inside and outside of the membranes of rough endoplasmic reticulum near the nuclei. Human hepatocyte growth factor is now known to be the same protein as scatter factor and tumor cytotoxic factor, both of which are produced by human fibroblasts in culture, but our results suggest that polymorphonuclear leukocytes in diseased livers are one cellular source of circulating human hepatocyte growth factor. The immunostaining properties of biliary epithelial cells in diseased livers also suggest that the cells produce and secrete human hepatocyte growth factor.

Adult↗

Association of HTLV-I antibody profile of asymptomatic carriers with proviral DNA levels of peripheral blood mononuclear cells.

The human T-lymphotropic virus type I (HTLV-I) antibody profile of 216 asymptomatic carriers in Miyazaki, Japan, was analyzed in conjunction with the HTLV-I proviral DNA levels in their peripheral blood mononuclear cells (PBMC) determined by the semiquantitative polymerase chain reaction (PCR) method. The geometric mean HTLV-I titer by particle agglutination assay (PA) of 58 subjects (27%) with a high DNA level was 1:1, 240; 94 (44%) with a medium DNA level, 1:740; 38 (18%) with a low level, 1:476; and, 26 (12%) with an undetectable level, 1:263. Moreover, when the subjects were divided into four groups according to titer from high to low, the correlation between DNA level and antibody titer level was highly significant (p < 0.0001). HTLV-I antibody subclass by Western blot (WB) was determined for 78 randomly selected samples from these carriers. Immunoglobulin (Ig) M antibody was detected in 35 (45%). The mean PA antibody titer was higher in carriers with IgM antibody than in those without, at each detectable proviral DNA level. These findings suggest that HTLV-I antibody titer is related to proviral DNA level and also to the presence of IgM antibodies among those with proviral DNA of the same level. Seven carriers (9%) were negative for IgG antibody by WB, among whom the proviral DNA level was low or undetectable and the PA titer was also low. Three of these were positive only for IgM antibody.

Aged↗

Enhancement of human hepatocyte growth factor production by interleukin-1 alpha and -1 beta and tumor necrosis factor-alpha by fibroblasts in culture.

Human hepatocyte growth factor (hHGF) was first purified from plasma of patients with fulminant hepatic failure (Gohda, E., Tsubouchi, H., Nakayama, H., Hirono, S., Sakiyama, O., Takahashi, K., Miyazaki, H., Hashimoto, S., and Daikuhara, Y. (1988) J. Clin. Invest. 81, 414-419) and is now identified to be the same protein as the scatter factor (Weidner, K. M., Arakaki, N., Hartmann, G., Vandekerckhove, J., Weingart, S., Rieder, H., Fonatsch, C., Tsubouchi, H., Hishida, T., Daikuhara, Y., and Birchmeier, W. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 7001-7005) and tumor cytotoxic factor (Shima, N., Nakao, M., Ogaki, F., Tsuda, E., Murakami, A., and Higashio, K. (1991) Biochem. Biophys. Res. Commun. 180, 1151-1158), and it is known to be produced by fibroblasts in culture. Here we report that inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) stimulate production of hHGF from human embryonic lung fibroblasts, MRC-5, and human gingival fibroblasts, GF-5. Recombinant human IL-1 alpha (rhIL-1 alpha) and recombinant human TNF-alpha (rhTNF-alpha) increased hHGF levels in culture supernatants of MRC-5 and GF-5 cells dose-dependently as determined by an enzyme-linked immunosorbent assay for hHGF. The half-maximal stimulatory concentrations of rhIL-1 alpha and rhTNF-alpha were about 1ng/ml and 10 units/ml, respectively. rhIL-1 beta showed almost the same effect as IL-1 alpha on stimulation of production of immunoreactive hHGF from the two cell lines. However, rhIL-6 failed to show the stimulatory effect on hHGF production by the cells in the range of 2-200 units/ml. Human interferon-beta and -gamma also did not show the stimulatory activity. Stimulation of hHGF production was observed 6-12 h after addition of rhIL-1 alpha or rhTNF-alpha and lasted at least 48 h, and the observed stimulation of hHGF production by cytokines was suppressed by addition of corresponding antiserum. hHGF mRNA levels of MRC-5 cells increased by addition of rhIL-1 alpha and rhTNF-alpha in a dose-dependent manner as determined by Northern blot analysis using cDNA for hHGF as a probe. In addition, results from nuclear run-off transcription experiments showed that the two cytokines regulated increasing hHGF gene expression at transcriptional levels rather than a change in mRNA stability. These observations indicate that the inflammatory cytokines modulate the production and secretion of hHGF by fibroblasts and may play an important role for tissue repair and regeneration.

Blotting, Northern↗

Development of a specific enzyme-linked immunosorbent assay for the hepatitis C virus antibody using clone 14.

The authors isolated a specific cDNA clone (clone 14) for non-A, non-B hepatitis virus infection. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) using a synthetic oligopeptide encoded by clone 14 and examined its usefulness for detecting hepatitis C virus (HCV) antibody in 181 patients with chronic NANB hepatitis, 88 with cirrhosis and 24 with hepatocellular carcinoma associated with NANB hepatitis virus. Anti-clone 14 antibody was detected in 75% of patients with chronic NANB hepatitis, 57% of cirrhotic patients and 58% hepatocellular carcinoma patients. Anticlone 14 and anti-C-100 antibody assayed using a commercial kit were found in serum from 199 (69%) and 205 (70%) of these 294 patients, respectively. Approximately 85% of the patients showed the presence of anticlone 14 and/or anti-C-100 antibodies. We compared the presence of these antibodies and the second generation anti-HCV antibody using ELISA and HCV RNA by the polymerase chain reaction assay, in the same blood samples from 49 patients with chronic liver disease who had anti-clone 14 and/or anti-C-100 antibody. HCV RNA was detected in 38 of 40 (95%) plasma samples containing anti-clone 14 antibody, the prevalence of which was similar to that for anti-C-100 antibody (41/42, 98%) and the second generation anti-HCV antibody (46/47, 98%). Furthermore, 6 of 7 plasma samples containing anti-clone 14 antibody and lacking anti-C-100 antibody were positive for the second generation anti-HCV antibody and HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[Successful chronic daily administration of oral etoposide for a case of adult T cell leukemia].

A 54-year-old woman with leucocytosis and skin lesion was hospitalized and diagnosed as chronic type adult T cell leukemia (ATL) in August 1989. Since her ATL cell count and LDH level increased after hospitalization, oral administration of etoposide was started at a dose of 100 mg/day for seven days. The oral administration of etoposide induced another chronic state of ATL. After 10 months without medication, she was readmitted because of an acute ATL crisis. After daily administration of etoposide at a dose of 50 mg/day, the white blood cell count and serum LDH level decreased to the normal range, and abnormal lymphocytes of peripheral blood disappeared. The low-dose daily administration of etoposide at a dose of 25 approximately 50 mg/day could be maintained over six months. No severe side effects except for alopecia and mild myelosuppression were noted during the treatment. Chronic daily administration of oral etoposide is one candidate for the treatment of ATL in an outpatient clinic.

Administration, Oral↗

The role of HGF-SF in animal and human hepatic physiology and pathology.

Hepatocyte growth factor (HGF) was first described as a hepatotrophic factor in partially hepatectomized rat plasma in the early 1980's and was purified from plasma of a patient with fulminant hepatic failure and from rat platelets in 1986-1987. Recent progress has revealed that HGF is the same protein as scatter factor and tumor cytotoxic factor, and is now known to be a broad-spectrum growth factor which stimulates cell growth not only of hepatocytes but also of many other types of epithelial and endothelial cells. In this review, however, we concentrate on the role of HGF, mainly human HGF, on liver regeneration after injury. In humans, plasma levels of hHGF increase to greater than 10 ng/ml during severe liver disease such as fulminant hepatic failure and decrease rapidly to normal levels when the patients recover from the disease. In less severe liver damage such as occurs in acute hepatitis, levels of hHGF in plasma increase to 0.5-1 ng/ml which is approaching the half maximal concentration for the stimulation of DNA synthesis in human hepatocytes in culture. Thus, HGF is believed to be involved in control of liver regeneration. Although the cell type(s) which produces HGF during liver disease is not yet identified, it is possible that circulating leukocytes or splenocytes are responsible. Synthesis of HGF is though to be regulated by a putative inducer(s) derived from damaged liver tissue. A control mechanism for HGF production during liver disease is proposed.

Animals↗