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Biomedical subjects

T Kawabe

Publications and source records attributed to T Kawabe.

At least 109 records · Page 6Linked to original sources

Stable carbon and nitrogen isotopic composition of diet and hair of Gidra-speaking Papuans.

The carbon and nitrogen stable isotopic composition of the scalp hair and diet of Gidra-speaking people in four villages in Papua New Guinea is presented. The isotopic composition of hair was measured, while that of the diet was estimated from food consumption survey data and the measured isotopic composition and protein and carbohydrate contents of food items. The average isotopic ratios of the hair samples and of the diet varied among the four study villages, which were selected because of their diverse ecological settings. Comparison was made between hair and calculated dietary isotopic compositions. Two of the four diet-hair enrichment values obtained for 13C (+1.8 and 2.2%) were similar to those previously reported (1.4-2.0%), but the other two values (3.7 and 4.8%) were greater than in earlier reports. 15N enrichment was systematically greater (by 1.0%) than reported values (4.3%) except for one village, where a much greater enrichment (6.9%) was found. The factors potentially relevant to these deviations are discussed. Possible errors in estimating the dietary isotopic composition and minor modifications of dietary habits revealed by food consumption surveys could explain most of the discrepancies. However, the great enrichment of 15N found in one of the villages remains unexplained.

Adult↗

Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity.

CD40-deficient mice are susceptible to Leishmania major infection while their wild-type littermates can resolve the infection. Upon stimulation with L. major antigens, draining lymph node T cells of the mutant mice and the susceptible mice, BALB/c, secrete comparable amounts of IL-4. The mutant mice produce less IFN gamma than wild-type mice. The expression of IL-12 p40 mRNA was significantly lower in L. major antigen-stimulated cells of mutant mice than those of wild-type or BALB/c mice. In normal mice, engagement of CD40 activates macrophages to a leishmanicidal state in vitro in the presence of IFN gamma. The results suggest that the CD40-CD40 ligand interaction plays an important role in two critical steps of cell-mediated immunity to L. major infection: the generation of a Th1 response and activation of macrophages to a leishmanicidal state.

Animals↗

Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease.

BACKGROUND & AIMS: We and others have previously shown that the mutation of K-ras codon 12 was found in the majority of pancreatic adenocarcinomas. The mutation has also been identified in the pancreatic duct with mucous cell hyperplasia in association with chronic pancreatitis. Ductal hyperplasia is also frequently found in the pancreas free from pancreatic carcinoma or chronic pancreatitis. The aim of this study was to assess the incidence and types of mutations in hyperplastic foci in these cases. METHODS: The nucleotide sequence of the K-ras gene at codon 12 of the DNA extracted from microdissected hyperplastic epithelium of the pancreatic duct obtained at autopsy in patients without pancreatic adenocarcinoma or chronic pancreatitis was analyzed. RESULTS: Of 38 patients with 79 hyperplastic foci, 12 patients (with 19 hyperplastic foci) had mutations. None of the 16 normal ducts in 12 specimens had this mutation. The nucleotide sequence of the codon in 53% of ductal hyperplastic foci was TGT or AGT, both of which were not found in 30 cases of adenocarcinoma. CONCLUSIONS: These results suggest that the ras gene mutation occurs frequently in multifocal hyperplastic foci of pancreatic duct and that the mutations may not have direct relevance to the carcinogenesis of pancreatic cancer.

Adult↗

Endoscopic papillary balloon dilation in cirrhotic patients: removal of common bile duct stones without sphincterotomy.

BACKGROUND AND STUDY AIMS: Endoscopic papillary balloon dilation (EPBD) is a less invasive alternative to endoscopic sphincterotomy (EST). This study reviews a series of cirrhotic patients with bile duct stones who were treated with EPBD. PATIENTS AND METHODS: EPBD was used to remove common bile duct stones in nine cirrhotic patients (one in Child-Pugh grade A, four in grade B, and four in grade C). After the papilla was dilated with balloon-tipped catheter, the stones were removed with a retrieval basket catheter or a retrieval balloon, or both. Mechanical lithotripsy was required in two patients with stones of more than 1 cm in diameter. RESULTS: Clearance of the common bile duct was achieved in all patients without any serious complications such as hemorrhage or perforation. CONCLUSIONS: These results suggest that EPBD is a safe and effective technique for the treatment of common bile duct stones in patients with liver cirrhosis.

Aged↗

Iron nutrition and anaemia in a malaria-endemic environment: haematological investigation of the Gidra-speaking population in lowland Papua New Guinea.

Blood examination was conducted for the four Gidra-speaking village groups in Papua New Guinea, who were characterized by high Fe intake and high malaria prevalence with marked inter-village differences. The northern riverine villagers, whose Fe intake was higher than the other three village groups, did not suffer from Fe-deficiency anaemia in their malaria-endemic environment; nor did the inland villagers, with their second highest Fe intake and their malaria-free environment, suffer from Fe-deficiency anaemia. However, several individuals of the southern riverine village suffered from anaemia in a malaria-endemic environment, although their Fe intake was almost the same as the inland villagers'. A considerable proportion of the coastal villagers were anaemic, reflecting the lowest Fe intake and the highest malaria prevalence. An inter-village comparison of the relationships between haemoglobin levels and transferrin saturation revealed that the southern riverine villagers needed smaller amounts of circulating Fe for erythropoiesis than the northern riverine and inland villagers, reflecting the long-term human-environment conditions such as the density of malaria vectors and the people's dietary habits. Fe supplementation was not judged effective against hypoferraemia and/or anaemia in such a population. As the incidence of malaria had no significant long-lasting effect on Fe stores or circulating Fe concentration, but did have an effect on anaemia, the hypothesis that malaria causes a transfer of Fe from the blood to parenchymal tissues as a defence against infectious diseases was not supported.

Anemia, Iron-Deficiency↗

Real-time monitoring of HCV-RNA by single tube assay kit and potential importance for predicting virological sustained response in patients with chronic hepatitis C.

In an attempt to predict virological sustained responders among patients with chronic hepatitis C after interferon therapy, HCV-RNA in serum was measured by a one tube RT-PCR assay kit using the RNA corresponding to 5 microL serum (standard assay) or 300 microL serum (enhanced-sensitivity assay). Dilution analysis revealed that sensitivity of the 'enhanced-sensitivity assay' increased by 10-100-fold when compared with a 'standard assay'. Using these assays, prospective study of interferon therapy on 38 HCV-RNA seropositive cases with chronic hepatitis (total amount 702 MU; duration of treatment 5-6 months) was performed. At the end of treatment, six were still positive and 32 became negative by the "standard assay', whereas an additional eight cases became positive (total 14 cases positive; the remaining 24 cases negative) by the 'enhanced-sensitivity assay'. Hepatitis C viral RNA state at the end of treatment remained the same 6 months later in 23 cases (61%) by a 'standard assay' and in 31 (82%) by the 'enhanced-sensitivity assay'. Of importance was that all patients (14 cases) demonstrating HCV-RNA in serum at the end of therapy, even by the "enhanced-sensitivity assay', did not show the disappearance of HCV-RNA in serum despite the long follow up. From these results, in order to improve our treatment efficacy, we should try to modify our treatment protocol to the extent that at least HCV-RNA becomes undetectable. That can be only feasible during treatment by real-time monitoring of HCV-RNA.

Adult↗

Ciliary neurotrophic factor prevents ischemia-induced learning disability and neuronal loss in gerbils.

Ciliary neurotrophic factor (CNTF) has been shown to have potent neurotrophic activity on peripheral and central neurons in vitro and in vivo. However, it remains to be determined whether or not CNTF rescues hippocampal CA1 neurons from lethal ischemia and prevents ischemia-induced learning disability. In the present in vivo study, we infused CNTF continuously for 7 days into the lateral ventricle of gerbil starting 2 h before 3-min forebrain ischemia. CNTF infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by the step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the strata moleculare, lacunosum/radiatum and oriens of the region were significantly more numerous in gerbils infused with CNTF than in those receiving vehicle infusion. These findings suggest that CNTF has a trophic effect on ischemic hippocampal neurons.

Animals↗

Suppression of cytokine production in T helper type 2 cells by nitric oxide in comparison with T helper type 1 cells.

We examined the effect of nitric oxide (NO) on cytokine production in T helper (Th) cell subsets, using murine splenic CD4+ T cells and two types of Th clones. Interferon-gamma-treated murine peritoneal exudate cells (IFN-PEC) suppressed DNA synthesis to 60% of the control level in CD4+ T cells stimulated with the anti-CD3 monoclonal antibody. The production of IL-2 and IL-4 in the CD4+ T cells decreased to 63.2% and 9.2%, respectively, of the control value by co-culture with IFN-PEC. The addition of NG-monomethyl-L-arginine (L-NMMA) partially recovered the suppression of DNA synthesis. In the presence of indomethacin, the suppression of DNA synthesis was partially inhibited and the reduction in the cytokine production caused by IFN-PEC was partially recovered. The simultaneous addition of NG-monomethyl-L-arginine (L-NMMA) and indomethacin completely inhibited not only the suppression of DNA synthesis but also the reduction in the cytokine production caused by IFN-PEC. Moreover, DNA synthesis in the Th2 clone was suppressed to a greater extent than that in the Th1 clone by co-culture with IFN-PEC. This suppression in the Th1 clone was inhibited by the addition of L-NMMA, whereas the DNA synthesis in the Th2 clone was not recovered by L-NMMA. In addition, sodium nitroprusside (SNP) suppressed IL-4 production in the Th2 clone but had no effect on IL-2 production in the Th1 clone. In the experiment of the co-culture with IFN-PEC, the inhibitory-effect of NO on T cell activation was not clarified by the influence of prostaglandins. However, in conclusion, cytokine production in Th2 cells may be more susceptible to NO than that in Th1 cells.

Animals↗

Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

Various growth factors are suggested to be involved in gastric mucosal repair. Our previous studies have shown that exogenous hepatocyte growth factor (HGF) has a proliferative effect on gastric epithelial cells. In the present study, comparison of the maximum proliferative effects and the optimum concentrations of several growth factors revealed that HGF was the most potent mitogen for gastric epithelial cells, as is the case for hepatocytes. Restitution of gastric epithelial cell monolayers was assessed using a round wound restitution model. HGF was the most effective agent for facilitating gastric epithelial restitution among those tested. A binding assay revealed specific binding of HGF to its receptor on gastric epithelial cells. Northern blot analysis confirmed the expression of specific HGF receptor mRNA (c-met) by gastric epithelial cells but not by gastric fibroblasts. To investigate endogenous HGF production, we determined the effect of gastric fibroblast-conditioned medium on epithelial proliferation and restitution. The conditioned medium produced similar effects to HGF and its activity was neutralized by an anti-HGF antibody. In addition, expression of HGF mRNA was detected in gastric fibroblasts but not in gastric epithelial cells. Our immunohistochemical study confirmed these in vitro data by means of demonstrating the existence and localization of HGF at human native gastric mucosa. HGF was localized at fibroblasts under the epithelial cell layer around gastric ulcers. These results suggest that HGF may be a potent endogenous promotor of gastric epithelial cell proliferation and migration, and may contribute to gastric mucosal repair through a paracrine mechanism.

Animals↗

Modulation of KC/gro protein (interleukin-8 related protein in rodents) release from hepatocytes by biologically active mediators.

Modulation of the release of KC/gro protein (a chemoattractant for neutrophils; IL-8 related protein in rodents) from isolated hepatocytes after stimulation with biologically active mediators was investigated. The release of KC/gro protein from hepatocytes of control rats was enhanced by stimulation with lipopolysaccharide, IL-1 beta or TNF-alpha in a dose-dependent manner, but was not enhanced by IL-6. In contrast, although spontaneous release of KC/gro protein from the hepatocytes of chronically ethanol-fed rats was markedly enhanced as compared with control rats, the relative increase by stimulation with lipopolysaccharide, IL-1 beta or TNF-alpha was significantly smaller than in controls. These findings suggest that the regulation of hepatocyte KC/gro protein production might be disturbed in chronically ethanol-fed rats.

Alcoholism↗

Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma.

We attempted to detect circulating hepatocellular carcinoma by demonstrating hepatocyte-associated mRNA in the nuclear cell component of peripheral blood using nested reverse transcription-polymerase chain reaction because of the extremely small number of tumor cells in the circulation. Albumin mRNA was demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse transcription-polymerase chain reaction. In contrast, alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating the possibility of using alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. alpha-Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17 cases of chronic hepatitis (12%). alpha-Fetoprotein mRNA was not demonstrated in 26 cases of normal healthy volunteers (0%). Among the patients with hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and serum alpha-fetoprotein level were markedly increased in the patients with alpha-fetoprotein mRNA in blood. In addition, alpha-fetoprotein mRNA was detected in the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.

Adult↗

Growth regulation of rabbit gastric epithelial cells and protooncogene expression.

We recently developed a primary culture system for gastric epithelial cells from adult rabbits that allows the investigation of growth regulation at the cellular level. In this study, we demonstrated that epidermal growth factor (EGF), insulin, and dibutyryl adenosine 3',5'-cyclic monophosphate (dBcAMP) all stimulated cell proliferation. Insulin and dBcAMP potentiated the stimulation of cell proliferation by EGF, while transforming growth factor-beta 1 (TGF-beta 1) inhibited it. Expression of c-fos and c-myc was induced in response to the stimulation by these growth regulators, but the degree of expression did not necessarily correlate with the effects of these agents on cell proliferation. In conclusion, EGF, insulin, and dBcAMP were positive growth regulators, while TGF-beta 1 was a negative regulator in gastric epithelial cells. These growth modulators may exert their effects by distinct pathways from a standpoint of the expression of c-fos and c-myc.

Animals↗