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Biomedical subjects

H Tsubouchi

Publications and source records attributed to H Tsubouchi.

At least 37 records · Page 2Linked to original sources

Transient activation of c-Jun NH2-terminal kinase by growth factors influences survival but not apoptosis of human thyrocytes.

Activation of c-Jun NH2-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is involved in apoptosis or cell proliferation. We have previously demonstrated that ionizing radiation or thyroid-stimulating hormone activated JNK without linking to thyroid cell apoptosis. To clarify the involvement of JNK activation in thyroid cell survival, we investigated the effects of various growth factors on induction of JNK activation in cultured human thyroid cells. JNK activation was observed at 30 minutes after fetal bovine serum (FBS) stimulation and returned to basal level at 240 minutes. Epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) also induced JNK activation, but did not trigger apoptotic cell death. Furthermore, we observed high basal activation of JNK in four of five human thyroid cancer cell lines. Overexpression of c-Met, an HGF receptor, was observed in two of the four cell lines with high basal JNK activity. Our results suggest that JNK activation does not induce apoptosis but is associated with survival or transformation of human thyroid cells.

Animals↗

[An adult case of systemic cat-scratch disease with hepatosplenic involvement].

A previously healthy 25-year-old female was admitted to our hospital in November, 1997, for treatment of a spike-fever of 2 weeks' duration. She had a cat in her house but reported no history of cat bites or scratches. No peripheral lymphadenopathy was detected. White blood cell count was within normal limits, but an increased C-reactive protein level of 11.4 mg/dl was noted. Infectious disease was suspected but ruled out as blood cultures were negative. Empiric therapy with clarithromyoin, isoniazid, and rifampicin was ineffective. In January, 1998, abdominal ultrasonogram revealed multiple hypoechoic mass lesions in the spleen and liver, and a splenectomy was performed in March. Histopathologic examination showed numerous necrotizing and caseating granulomas, which tested positive for Bartonella henselae DNA by PCR. Furthermore, the patient tested positive for B. henselae antibody by immunofluorescence assay. A diagnosis of systemic cat-scratch disease with hepatospnenic involvement was made. Combination therapy with minocycline, sulbactam/cefoperazone, and tosufloxacin was administered and her inflammatory findings improved gradually. We report an adult case of systemic cat-scratch disease with liver and spleen involvement in the non-immunocompromised host.

Adult↗

[Primary splenic CD8-positive diffuse large B-cell lymphoma].

A 71-year-old woman was admitted for further examination of an increased serum LDH level. Abdominal ultrasonography and CT scan showed a large tumor in her spleen. Because malignant lymphoma was suspected, the spleen was removed for diagnosis and treatment planning. The histopathological and immunohistochemical features of the tumor indicated diffuse large B-cell lymphoma (DLBL). The flow-cytometric immunophenotype of the lymphoma cells was CD2-, CD3-, CD4-, CD5-, CD8+, CD10+, CD19+, CD20+, CD23-, kappa+, lambda-, CD25+, and CD56-. From these findings, the patient was diagnosed as having CD8+ DLBL. To our knowledge, this is the first reported case of primary splenic CD8-positive DLBL.

Aged↗

Development of highly sensitive enzyme-linked immunosorbent assays for hepatocyte growth factor/scatter factor (HGF/SF): determination of HGF/SF in serum and urine from normal human subjects.

A sandwich enzyme-linked immunosorbent assay (ELISA) using rabbit anti-hepatocyte growth factor (HGF) IgG for human HGF, also known as the scatter factor, has previously been developed for determining increases in serum HGF levels in various liver diseases. The sensitivity limit of the ELISA is, however, approximately 0.2 ng/ml sample, and HGF concentrations in about 50% of normal subjects are not accurately measurable by this method, because the mean level of HGF in normal serum is close to the sensitivity limit. In the present study, chicken Fab' from egg yolk anti-HGF immunoglobulin Y and rabbit Fab' from rabbit anti-HGF IgG were conjugated with beta-D-galactosidase. With these conjugates as the second antibodies, we developed two sandwich ELISAs for human HGF and found that the sensitivities were about 20 pg/ml with the former conjugate and 2 pg/ml with the latter. The HGF concentration in sera from 138 normal subjects determined by the ELISA with the rabbit conjugate was 244+/-65 (SD) pg/ml serum, and it correlated very well with the number of leukocytes. Moreover, the ELISA with the rabbit conjugate permitted the determination of HGF levels in urine from normal subjects without first concentrating the sample. The determination of HGF in various biological fluids other than blood and urine by these ELISAs may aid the diagnosis and prognosis of various diseases.

Adult↗

Inflammatory pseudotumor of the liver diagnosed by needle liver biopsy under ultrasonographic tomography guidance.

Inflammatory pseudotumor of the liver is a rare benign lesion, but exploratory laparotomy and a hepatectomy are often performed unnecessarily after various misdiagnoses, including liver abscess, hepatocellular carcinoma, metastatic liver tumor, and cholangiocarcinoma. We present a case of hepatic inflammatory pseudotumor in a 17-year-old man in whom diagnosis was confirmed by liver needle biopsy under ultrasonographic tomography (UST) guidance. He had complained of fever and right hypochondralgia 2 months after being operated for appendicitis. He was admitted to our hospital because of the persistence of these symptoms and the presence of a hepatic mass lesion detected by UST. He had hepatomegaly, with tenderness; leukocytosis and elevated erythrocyte sedimentation rate and C-reactive protein level were noted. UST showed a hypoechoic mass in the liver and pre-contrast computerized tomography (CT) revealed a low-density area with an ill defined margin, which was barely enhanced by the contrast medium. On the basis of the patient's clinical symptoms and the laboratory data and imaging studies, the presence of a liver abscess was suspected and antibiotics were administered. One month after the initiation of the antibiotic therapy, UST demonstrated that the portal vein had dilated serpiginously and penetrated into the mass. As the heterogeneous appearance displayed by post-enhanced CT indicated the need for a differential diagnosis of the hepatic mass lesion to rule out hepatocellular carcinoma, percutaneous needle biopsy was performed, under UST guidance. Histopathological examination demonstrated marked infiltration of plasma cells and fibrosis, findings which were consistent with those of hepatic inflammatory pseudotumor. There was a spontaneous reduction of the hepatic pseudotumor without continuous antibiotics and this reduction was documented on follow-up UST and CT.

Adolescent↗

A case of chronic hepatitis C developing insulin-dependent diabetes mellitus associated with various autoantibodies during interferon therapy.

We report a case of chronic hepatitis C presenting insulin-dependent diabetes mellitus (IDDM) associated with various autoantibodies including possible anti-insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis received IFN therapy. The thyroid function was well-controlled by administration of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks after starting IFN (reaching 530 million units of total dose), marked thirst happened, with increased fasting plasma glucose level (488 mg/dl) and decreased daily urinary C peptide immunoreactivity level (less than 4.2 microg/day). IDDM occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA, and thyroid autoantibodies titers increased, but without pancreatic islet cell antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was stopped and insulin treatment was started, but plasma glucose level was not controlled well. AIRA became negative 2 months later, however, insulin antibody (IA) was positive when tested after 18 months. Serum HCV RNA has been negative, and a normal level of serum transaminase has been observed since IFN therapy. It is likely that IFN therapy induced the immunological disturbance and resulted in occurrence of various autoantibodies and IDDM in the patient.

Antibodies, Antinuclear↗

A case of acute hepatitis A with marked hemophagocytosis in bone marrow.

A previously well 18-year-old female was referred to our hospital because of abnormalities of blood biochemistry and slight jaundice. Because serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated more than 6000 IU/L, the patient was suspected to have acute viral hepatitis. The platelet count on admission was 9.7x10(4)/µl, which was decreased from the initial value of 21x10(4)/µl for 3 days. The coagulation tests revealed marked elevation of D-dimmer, fibrinogen degradation products and thrombin-antithrombin III complex suggesting increase in fibrinolysis. Serum levels of high density lipoprotein cholesterol and ferritin were markedly decreased and increased, respectively. The bone marrow smears revealed proliferation of mature histiocytes ingesting platelets and erythrocytes, these pathological findings were consistent with those of hemophagocytic syndrome (HPS). In addition, anti-hepatitis A IgM antibody in the serum and hepatitis A virus (HAV) RNA in the stool were positive. Therefore, the patient was diagnosed as having acute hepatitis A with probable HPS. Since a fulminant clinical course was suspected, glucocorticoid pulse therapy was started immediately 7 days after onset and a favorable clinical outcome resulted.

Journal Article↗

Hepatocyte growth factor/scatter factor enhances the thrombopoietin mRNA expression in rat hepatocytes and cirrhotic rat livers.

BACKGROUND: Although thrombopoietin (TPO) is mainly produced in the liver, the regulatory mechanism of TPO gene expression in hepatocytes remains unclear. The role of TPO in thrombocytopenia associated with liver cirrhosis has not been identified. METHODS: We examined the effects of various growth factors and cytokines on TPO mRNA expression in adult rat hepatocytes in primary cultures using a semiquantitative reverse transcription-polymerase chain reaction assay. RESULTS: Among them, only hepatocyte growth factor/scatter factor (HGF/SF) enhanced TPO mRNA expression; other growth factors (epidermal growth factor and transforming growth factor-beta) and cytokines (erythropoietin, granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor, interleukin (IL)-3, IL-6 and interferon-gamma) did not. Next, we examined TPO mRNA expression in the livers of rats with CCl4-induced cirrhosis, the effects of HGF/SF on hepatic TPO mRNA expression and peripheral platelet and bone marrow megakaryocyte counts in the cirrhotic rats. In the cirrhotic rats, both the peripheral platelet count and TPO mRNA expression in the livers were markedly decreased compared with those of the normal rats. The administration of HGF/SF to the cirrhotic rats stimulated TPO mRNA expression in the livers and resulted in significant increases of peripheral platelets and bone marrow megakaryocytes. CONCLUSIONS: These results suggest that HGF/SF is a possible regulatory factor for TPO gene expression and that HGF/SF increases platelet production through an enhancement of TPO mRNA expression in the livers of cirrhotic rats.

Animals↗

A follow-up study of morbidity and mortality associated with hepatitis C virus infection and its interaction with human T lymphotropic virus type I in Miyazaki, Japan.

A follow-up study was performed to analyze the effects of hepatitis C virus (HCV) infection on morbidity and mortality in the adult population from a village in Japan found to have endemic levels of both HCV and human T lymphotropic virus type I (HTLV-I). By use of the Cox proportional hazards model, rate ratios (RRs) and 95% confidence intervals (CIs) were estimated. Strong, significant effects of seropositivity for antibodies to HCV on self-reported incident liver disease (RR, 3.5; 95% CI, 1.9-6.4) and on death due to liver cancer (RR, 8.2; 95% CI, 1.6-41.4) were observed. Dual infection with HCV and HTLV-I seemed to have a synergistic effect on incident liver disease (RR, 5.9) as well as on death from liver cancer (RR, 21.9). HCV infection also was positively, although not significantly, associated with reported incident diabetes. Our findings suggest that coinfection with HTLV-I may affect the course of HCV-associated disease.

Adolescent↗

Biological activities of the lectin, abrin-a, against human lymphocytes and cultured leukemic cell lines.

The cytoagglutination by abrin-a against human cultured cell lines derived from acute lymphoblastic leukemia (ALL) and human peripheral blood lymphocytes obtained from normal adults and from patients with adult T cell leukemia (ATL) was investigated. Among acute T lymphoblastic leukemia (T-ALL) cell lines, abrin-a showed strong cytoagglutination against relatively differentiated cell lines, such as Jurkat and CCRF-HSB-2. Among acute B lymphoblastic leukemia (B-ALL) cell lines, abrin-a strongly agglutinated an immature cell line, NALM6. In comparison with ALL cell lines, cytoagglutination by abrin-a against normal lymphocytes was weak. Abrin-a showed higher cytoagglutination against lymphocytes derived from ATL than lymphocytes derived from normal adults. In connection with the cytoagglutination, abrin-a-induced cytotoxicity against human cultured leukemic cell lines was evaluated. In proportion to the extent of cytoagglutination, abrin-a induced cytotoxicity in Jurkat, CCRF-HSB-2, MOLT-4, RPMI8402, and BALL-1 as well. Although CCRF-CEM and BALM-1 were both weakly agglutinated by abrin-a, these cell lines were very sensitive to the abrin-a-induced cytotoxicity. NALM6 was strongly agglutinated by abrin-a, but abrin-a exhibited less strong cytotoxicity against this cell line. These results suggest the feasible application of abrin-a as a tool to distinguish the human leukemic cells and its potential for clinical application.

Abrin↗

Exo1 roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae.

The MRE11, RAD50, and XRS2 genes of Saccharomyces cerevisiae are involved in the repair of DNA double-strand breaks (DSBs) produced by ionizing radiation and by radiomimetic chemicals such as methyl methanesulfonate (MMS). In these mutants, single-strand DNA degradation in a 5' to 3' direction from DSB ends is reduced. Multiple copies of the EXO1 gene, encoding a 5' to 3' double-strand DNA exonuclease, were found to suppress the high MMS sensitivity of these mutants. The exo1 single mutant shows weak MMS sensitivity. When an exo1 mutation is combined with an mre11 mutation, both repair of MMS-induced damage and processing of DSBs are more severely reduced than in either single mutant, suggesting that Exo1 and Mre11 function independently in DSB processing. During meiosis, transcription of the EXO1 gene is highly induced. In meiotic cells, the exo1 mutation reduces the processing of DSBs and the frequency of crossing over, but not the frequency of gene conversion. These results suggest that Exo1 functions in the processing of DSB ends and in meiotic crossing over.

Crossing Over, Genetic↗

[Tracheal tube/laryngeal mask exchange to prevent coughing in lung volume reduction surgery].

We report the use of laryngeal mask airway (LMA) to facilitate smooth emergence from anesthesia in 3 patients who underwent lung volume reduction surgery (LVRS) for severely symptomatic emphysema. To prevent coughing during emergence we replaced the endotracheal tube with LMA while patient was still in deep anesthesia. Emergence was smooth without coughing in all three patients, and ventilation with facemask was not needed after removal of LMA. We believe this technique is safe and beneficial for anesthetic management of LVRS.

Aged↗

[Copper deficiency anemia and neutropenia secondary to total gastrectomy].

We report a case of copper deficiency with anemia and neutropenia due to dumping syndrome after total gastrectomy. Parenteral nutrition containing cupric sulfate promptly improved the dumping syndrome, anemia and neutropenia. This case suggests that total gastrectomy with dumping syndrome can cause copper deficiency, and that copper deficiency should be considered when encountering similar patients with severe anemia and neutropenia.

Anemia↗

[A case of mixed connective tissue disease with lupus-like manifestations of the central nervous system, successfully treated with cyclophosphamide combined with prednisolone].

A 29-year-old woman experienced Raynaud's phenomenon, swelling of her fingers, eruptions on her face, and muscle weakness in 1990. She was diagnosed as having mixed connective tissue disease (MCTD) and was treated with prednisolone (PSL) for 3 years. Most of her complaints disappeared after the treatment. In March 1997, she experienced fever, erythema, and lymphadenopathy. Although she was treated with PSL (20 mg/day) again, muscle weakness, mental disturbance, and recto-urinary disturbance appeared. When she was re-admitted to our hospital, increased levels of muscle-derived enzymes and positivity of anti-RNP antibody were found. High signal areas in her cerebrum were shown by magnetic resonance imaging, and slow and spike pattern was shown by electroencephalography. Hypoperfusion of the cerebral blood flow was suggested on single photon emission computed tomography. The number of mononuclear cells, amount of protein and level of interleukin-6 were found to be elevated in her cerebrospinal fluid (CSF). Her neurological manifestations were diagnosed as being due to MCTD, and showed characteristics similar to those of systemic lupus erythematosus. She was treated with PSL (60 mg/day) followed by steroid pulse therapy. Because the response to this treatment was partial, oral administration of cyclophosphamide (CPM) (100 mg/day) was added. Muscle weakness and neurological abnormalities as well as abnormal laboratory findings gradually improved over the following two months. We conclude that the treatment with CPM combined with PSL may be useful, when neurological manifestations of MCTD are serious and resistant to conventional therapy.

Adult↗