Biomedical subjects

Nobuharu Ohshima

Publications and source records attributed to Nobuharu Ohshima.

5 recordsLinked to original sources

PubMed2006

[Tuberculosis complicated with liver cirrhosis].

OBJECTIVES: The aim of this study is to examine the clinical characteristics of tuberculous patients complicated with liver cirrhosis. MATERIALS AND METHODS: 44 patients (39 males and 5 females) admitted to Tokyo National Hospital since 1991 till 2005 were analysed. RESULTS: Eighteen patients died and liver failure was the leading cause of death (N = 10). Hepatitis C viral infection (N = 17), and excessive alcohol consumption (N = 13) were the major causes of liver cirrhosis. Twenty five patients followed-up for more than 3 months were further selected for the detailed analyses. Multi-drug combination chemotherapy including isoniazid, rifampicin and ethambutol was administered in 22 patients. Adverse effects were seen in 20 patients. The numbers of patients with leukopenia, thrombocytopenia and hyperbilirubinemia were 10, 9 and 3, respectively. They recovered following the alteration of chemotherapeutic regimen or drug desensitization. CONCLUSION: Tuberculous patients with liver cirrhosis are characterized with higher mortality rate and higher frequency of adverse effects of antituberculous chemotherapy. Multi-drug combination regimen could be tolerable under adequate surveillance of side effects even in the situation of preexisting liver dysfunction.

Adult↗

PubMed2002

Regulation of human B cell function by sulfasalazine and its metabolites.

Although sulfasalazine is a well-known disease-modifying antirheumatic drug (DMARD), the mechanisms of its action remain unclear. Indeed, it remains uncertain whether sulfasalazine itself or one of its metabolites is responsible for the antirheumatic effects of sulfasalazine. Since one of the characteristic features of rheumatoid arthritis (RA) is chronic stimulation of B cells, we compared the effects of sulfasalazine and its metabolites on the in vitro function of human B cells. Ig production was induced from highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. Sulfasalazine suppressed the production of IgM and IgG at its pharmacologically attainable concentrations (1-10 microg/ml). Of the metabolites of sulfasalazine, sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA), but not 4-acethyl SP, also significantly suppressed the production of IgM and IgG at their pharmacologically relevant concentrations. By contrast, any of sulfasalazine, SP, 5-ASA and 4-acethyl SP did not suppress the IFN-gamma production of immobilized anti-CD3 stimulated CD4+ T cells. These results indicate that sulfasalazine and its metabolites preferentially suppress the function of B cells, but not that of T cells, at their pharmacologically attainable concentrations. The data therefore suggest that not only sulfasalazine, but its metabolites, might contribute to the beneficial effects of sulfasalazine.

Animals↗

PubMed2002

A functional study on CysLT(1) receptors in human eosinophils.

BACKGROUND: The cysteinyl leukotrienes (CysLTs) mediate their biological actions through two receptors: CysLT(1) receptor and CysLT(2) receptor. OBJECTIVE: This study was undertaken to examine the direct effects of CysLTs on eosinophils, such as chemotaxis and degranulation, focusing on CysLT(1). METHODS: Eosinophils were isolated from venous blood from normal volunteers who had no history of allergy (purity >99%). They were subjected to reverse transcription-PCR analysis and flow-cytometric analysis for CysLT(1). Binding assays were performed with [(3)H]LTD(4). Purified eosinophils loaded with Fura-2 acetoxymethyl ester were stimulated with CysLTs, and Ca(2+) influx was measured. Eosinophil migration in response to CysLTs was measured using a 96-well multiwell Boyden chamber. Eosinophils were treated with LTD(4) at 10(-6) M for 60 min followed by incubation for 4 h at 37 degrees C in the presence or absence of IL-5 and eosinophil-derived neurotoxin (EDN) release was evaluated. RESULTS: The expression of the mRNA and protein of CysLT(1) on eosinophils and [(3)H]LTD(4)-specific binding to eosinophils were observed. Neither Th1 cytokine (IFN-gamma) nor Th2 cytokines (IL-4 or IL-5) affected CysLT(1) expression in eosinophils. CysLTs induced an increase in intracellular free Ca(2+) in eosinophils via CysLT(1), as suggested by the efficient inhibition by a CysLT(1) antagonist, pranlukast, in addition to the rank order of potency being LTD(4), LTC(4) and LTE(4). LTD(4) stimulated eosinophils to migrate at 10(-6) M via CysLT(1). LTE(4) also induced significant eosinophil migration at 10(-6) M. LTD(4) enhanced EDN release induced by IL-5 via CysLT(1). CONCLUSION: CysLTs induce migration and enhance degranulation in eosinophils via CysLT(1). Accordingly, interaction of CysLTs and CysLT(1) on eosinophils has the potential to play a prominent role in the pathophysiology of asthma.

Calcium↗

PubMedDate not supplied

Apoptosis-inducing activity of trihaloacetylazulenes against human oral tumor cell lines.

Twenty-six trihaloacetylazulene derivatives were investigated for their tumor-specific cytotoxicity and apoptosis-inducing activity against three human normal cells (HGF, HPC, HPLF) and four human tumor cell lines (HSC-2, HSC-3, HSC-4, HL-60). The trichloroacetylazulenes [1b-13b] generally showed higher cytotoxicity as compared to the corresponding trifluoroacetylazulenes [1a-13a]. The trichloroacetylazulenes [1b-13b] also showed higher tumor-specific cytotoxicity (expressed as TS value) than the corresponding trifluoroacetylazulenes [1a-13a]. Especially, 2,3-dimethyl-1-trichloroacetylazulene [5b] and 1,3-ditrichloroacetyl-4,6,8-trimethylazulene [11b] showed the highest cytotoxicity and tumor specificity (TS > 35.6 and > 44.1, respectively). These compounds induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 and HSC-3 cells, but activated caspase-3, -8 and -9 in all of these cells, suggesting the activation of both mitochondria-independent (extrinsic) and dependent (intrinsic) pathways. Western blot analysis showed that two compounds [5b, 11b] slightly increased the intracellular concentration of pro-apoptotic proteins (Bad, Bax) in HSC-2 cells. None of the 26 compounds showed anti-HIV activity. These results suggest [5b] and [11b] as possible candidates for future cancer chemotherapy.

Apoptosis↗

PubMedDate not supplied

Inhibition of NO production in LPS-stimulated mouse macrophage-like cells by trihaloacetylazulenes.

The effects of 26 trihaloacetylazulene derivatives on nitric oxide (NO) production by the mouse macrophage-like Raw 264.7 cells was investigated. The trichloroacetylazulenes [1b-13b] generally showed higher cytotoxicity as compared with the corresponding trifluoroacetylazulenes [1a-13a]. All the compounds inhibited NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to various extents. 3-Trifluoroacetylguaiazulene [8a], 1-trifluoroacetyl-4,6,8-trimethylazulene [10a], 3-methyl-l-trichloroacetylazulene [2b] and 3-ethyl-1-trichloroacetylazulene [3b] showed lower cytotoxic activity and most effectively inhibited NO production. Western blot analysis revealed that compounds [8a, 1Oal dose-dependently reduced the intracellular concentration of inducible NO synthase (iNOS), whereas compounds [2b, 3b] only marginally affected the iNOS protein expression. RT-PCR analysis showed that compounds [8a, 2b] reduced the iNOS mRNA expression by approximately 50%. These compounds affected cyclooxygenase-2 protein and mRNA expression, depending on the concentrations. ESR spectroscopy revealed that compounds [8a, 10a, 2b, 3b] neither produced radical, nor scavenged NO, superoxide anion or diphenyl-2-picrylhydrazyl radicals. The present study showed the inhibitory effects of trifluoroacetylazulenes and trichloroacetylazulenes on NO production by activated macrophages.

Animals↗