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Biomedical subjects

K Kobashi

Publications and source records attributed to K Kobashi.

204 records · Page 12Linked to original sources
PubMedDate not supplied

Hydrolysis of glycyrrhizin to 18 beta-glycyrrhetyl monoglucuronide by lysosomal beta-D-glucuronidase of animal livers.

Glycyrrhizin (GL), a main constituent of liquorice, was hydrolysed to 18 beta-glycyrrhetic acid mono-beta-D-glucuronide (GAMG, glycyrrhetyl monoglucuronide) by rat liver homogenate, and the hydrolytic activity was localized in the lysosomes among the same subcellular fractions as acid beta-D-glucuronidase activity (p-nitrophenyl beta-D-glucuronide (pNPG)-hydrolysing activity). Rat liver lysosomes hydrolysed GAMG to 18 beta-glycyrrhetic acid (GA) at only 30% rate compared with the rate of GL to GAMG. GA was also produced slowly from GL after time lag by the lysosomes. Thus, GL seems to be first hydrolysed to GAMG, which was successively hydrolysed slowly to GA. GL-hydrolysing activity was released together with acid beta-D-glucuronidase activity from the lysosomes by sonication. Both activities from the sonicated lysosomes were eluted coincidentally on Sephacryl S-300 and butyl-Toyopearl 650M column chromatography, indicating that both activities are exhibited by the same enzyme. Moreover, GL-hydrolysing activity was inhibited strongly with D-saccharic acid 1,4-lactone, a specific inhibitor beta-D-glucuronidases of various origins. pH optimum of GL-hydrolysing activity was found to be 5.6, different from that (less than 4.0) of pNPG-hydrolysing activity. Km for GL was found to be 2 x 10(-5) M. Although hepatic lysosomes from mouse and cattle hydrolysed GAMG to GA similarly to those from rat, the hydrolysis of GAMG was not detected in lysosomes of human and porcine livers. Accordingly, lysosomal beta-D-glucuronidases from human and porcine livers converted GL to GAMG only.

Animals↗
PubMedDate not supplied

Metabolism of homoorientin by human intestinal bacteria.

As a part of our studies on the metabolism of bioactive compounds from oriental medicines by intestinal flora, homoorientin, a C-glycosylflavonoid, was anaerobically incubated with a human intestinal bacterial mixture. Homoorientin was transformed to 6-C-glucosyleriodictyol, (+/-)-eriodictyol, luteolin, 3,4-dihydroxyphenylpropionic acid, and phloroglucinol. A novel cleavage of the C-glycosyl bond was discovered for the first time by using intestinal bacteria.

Bacteria, Anaerobic↗
PubMedDate not supplied

Functional expression of Fas and Fas ligand on human colonic intraepithelial T lymphocytes.

The expression of Fas, a cell surface receptor directly responsible for triggering cell death by apoptosis, and its ligand (FasL) was investigated on both human colonic intraepithelial T lymphocytes (IELs) and peripheral blood mononuclear lymphocytes (PBMLs). FACS analysis indicated that IELs have increased expression of Fas compared with PBMLs, together with the progress activation marker, CD45RO. A discrete fraction of freshly isolated IELs also constitutively expressed FasL, perhaps as a result of recent in vivo activation. Using monoclonal antibody APO2.7, which detects mitochondrial 7A6 antigen specifically expressed by cells undergoing apoptosis, we further investigated the apoptosis-inducing effect of anti-Fas monoclonal antibody (CH11) on both IELs and PBMLs. FACS analysis revealed that CH11 increased the percentage of apoptotic cells, in IELs but not in PBMLs. Culture with anti-FasL monoclonal antibody (4H9) significantly recovered cell viability in IELs, but not in PBMLs. These results indicate that IELs constitutively express both Fas and FasL and that Fas crosslinking generates signals resulting in apoptosis, outlining a potential mechanism involved in intestinal tolerance.

Adult↗
PubMedDate not supplied

Spontaneous rupture of hepatocellular carcinoma of the caudate lobe.

A rare case of ruptured hepatocellular carcinoma (HCC) of the caudate lobe is reported. A 67-year-old man came to the hospital with complaints of abdominal pain and distension. Computed tomography (CT) showed haemoperitoneum and a mass in the caudate lobe. Angiography demonstrated a tumor stain. However, extravasation of the contrast medium was not clear. Although transcatheter arterial embolization (TAE) was performed, bleeding from the tumor could not be controlled. The caudate lobe, including the tumor, was resected. The patient died of multiple organ failure despite intensive care. This case suggests that TAE is not always effective and may not be safely or easily performed when treating ruptured HCC in the caudate lobe. This is attributed to the multiple feeding arteries of the tumor, derived from the proximal portion of the right and left hepatic arteries. If bleeding from the ruptured HCC in the caudate lobe is not controlled, immediate resection of the tumor is recommended.

Aged↗
PubMedDate not supplied

Down-regulation of IL-18 receptor in cancer patients: its clinical significance.

Interleukin-18 (IL-18) is a powerful inducer of interferon-gamma (IFN-gamma), a key immunoregulatory cytokine. Cellular immune responsiveness, as measured by IL-18-induced IFN-gamma production from peripheral blood mononuclear cells (PBMCs) in ELISA assay, was evaluated in 10 patients with advanced cancer and in 10 normal controls. Supernatant levels of IFN-gamma were detected at 2 hours after PBMCs culture and markedly increased thereafter in healthy volunteers. In contrast, IFN-gamma production in cancer patients was not detected during the culture period (0-72 hours). We also measured IL-18-stimulated IL-12 production in healthy volunteers and null response was observed in cancer-bearing patients. Next, we studied mRNA expressions of IL-18 receptor (IL-18R) and IFN-gamma in PBMCs in cancer patients and healthy volunteers by RT-PCR assay. Both mRNA levels of IL-18R and IFN-gamma were significantly decreased in cancer-bearing patients compared with normal controls. These results suggested that IL-18 responsiveness for IFN-gamma production in cancer-bearing patients was impaired. Using flow cytometric analysis, we studied T-cell subsets, CD3- CD56+ (NK cell), CD3+ CD45RO+ (memory T-cell), CD3+ CD95+ (Fas+ T-cell), CD3+ CD4+ (helper T-cell), CD3+ CD8+ (cytotoxic T-cell: CTL) and CD3+ V alpha24+ (NKT-cell), in cancer patients and normal controls. The NK and cytotoxic T-cells significantly decreased and NKT-cells had decreased tendency in cancer patients compared with normal controls. In contrast, memory T cells, Fas+ T-cells and helper T-cells were all significantly increased in cancer patients compared with normal controls. These results suggested that the underlying mechanism of impaired IL-18 responsiveness in PBMCs from cancer-bearing patients was, at least in part, ascribed to a drastic decrease of NK cells and CTL which constitutively and highly express IL-18R and also attributed to null production of IL-12 which up-regulates IL-18R.

Adult↗