Helicobacter pylori infection and progression of gastric atrophy and intestinal metaplasia.
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Biomedical subjects
Publications and source records attributed to M Takashima.
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Two strains of ballistocondium-forming yeasts, isolated from plants collected in the south-east seacoast of Bangkok, Thailand, were described. The strains (K-272(T) and K-337(T)) were assigned to the genera Bullera and Kockovaella, respectively, based on morphological and chemotaxonomical characteristics. Phylogenetically, strain K-272(T) is close to Bullera hannae, and strain K-337(T) is close to Kockovaella thailandica and Kockovaella imperatae. These two strains represent new species based on DNA-DNA reassociation experiments. Bullera penniseticola Takashima et Nakase sp. nov. and Kockovaella sacchari Takashima et Nakase sp. nov. are proposed for K-272(T) (=JCM 9857(T)) and K-337(T) (=JCM 9858(T)), respectively.
Helicobacter pylori is present in infected patients not only on the gastric epithelial cell surface but also in gastric mucus. We developed a competitive polymerase chain reaction (cPCR) method for quantitative measurement of H. pylori in gastric mucus. The aim of this study was to determine the number of H. pylori in gastric mucus before and after anti-H. pylori treatment. Patients with duodenal ulcer were treated with lansoprazole alone (n = 11) or lansoprazole and amoxycillin (n = 12). The amount of H. pylori in gastric mucus was measured over time by a cPCR assay. Helicobacter pylori infection was also tested for using histology, culture, and the rapid urease test (RUT). Although most patients treated with lansoprazole alone had become H. pylori-negative by the end of treatment when tested by histology, RUT, and culture, a large number of H. pylori organisms were found in the gastric mucus at that time by cPCR. These patients returned to being H. pylori positive 1 to 12 months later on the basis of histology, RUT, and culture. However, cPCR results indicated eradication of H. pylori by the end of treatment in eight of the 12 patients treated with lansoprazole and amoxicillin, and these patients remained H. pylori negative on histology, RUT, culture, and cPCR 1 to 12 months later. Testing for H. pylori in gastric mucus is thus useful for precise determination of the success or failure of H. pylori eradication therapy.
KB-2796, a novel calcium channel blocker, is under development as an anti-migraine drug. We examined its effects on spreading depression (SD) in rat hippocampal slices as compared with those of flunarizine, dimetotiazine and sumatriptan. Extracellular recording was made from the CA1 subfield. An SD, followed by a series of spontaneous SDs, was induced by a brief period of hypoxia (40-60 sec). The latency of initiated SD and the interval between the initiated and subsequent spontaneous SDs were examined. KB-2796 significantly prolonged both latency and interval in a concentration-dependent manner (10(-10)-10(-8) M). KB-2796 was about 1,000 and 10 times more potent than flunarizine in prolonging the latency and interval, respectively. However, dimetotiazine and sumatriptan did not show any activity at 10(-7) and 10(-6) M. the effect of KB-2796 on SD may be due to their calcium channel blocking effects.
The effects of 3-[bis(4-hydroxyphenyl)methyl]-2-[4-(2-chlorophenyl)- piperazin-1-ylcarbonyl]-1-(2-dimethylamino ethyl) indole methanesulfonate (KW-8232) on the bone turnover in ovariectomized (OVX) rats were studied by the oral administration for 6 weeks. KW-8232 inhibited the decreased bone mineral densities of the femur and tibia in OVX rats. OVX induced the increase of serum alkaline phosphatase and osteocalcin levels, markers of high bone turnover, and also increased urinary hydroxyproline, pyridinoline and deoxypyridinoline excretion, markers of bone resorption. KW-8232 significantly inhibited the increase of serum alkaline phosphatase level at doses of 10 and 30 mg/kg and the increase of osteocalcin level at a dose of 3 mg/kg. KW-8232 (1 mg/kg) markedly suppressed the OVX-induced increase of urinary hydroxyproline, pyridinoline and deoxypyridinoline excretion. KW-8232 didn't affect serum calcium level, but significantly decreased urinary calcium excretion at doses of 10 and 30 mg/kg. These results suggest that KW-8232 decreased bone loss in this model by suppressing bone resorption.
The purpose of this study was to evaluate the effects of 3-[bis(4-hydroxyphenyl)methyl]-2-[4-(2-chlorophenyl)-piperazin-1-+ ++ylcarbonyl]-1-(2-dimethylaminoethyl) indole methanesulfonate (KW-8232), a novel anti-osteoporotic agent, on bone loss in neurectomized rats. We also investigated the effect of KW-8232 on bone resorption in this animal model. Male Sprague-Dawley rats underwent unilateral hind-limb immobilization by sciatic neurectomy. KW-8232 (3, 10 and 30 mg/kg, p.o.) was effective in inhibiting femoral bone loss. KW-8232 decreased urinary pyridinoline and deoxypyridinoline excretion. These results indicate that KW-8232 effectively prevents the bone loss due to immobilization.
Serum apo(a) isoform sizes were determined by SDS-polyacryl amide gel electrophoretic (PAGE) method, followed by a high sensitive immunoblotting. The relation between the number of apo(a) kringle IV encoding sequences in the apo(a) gene, as assessed by pulsed field gel electrophoresis and genomic blotting (genotype), and the apo(a) isoforms (phenotype) in SDS-PAGE was evaluated in 78 individuals. The correlation of apo(a) allele number between phenotype and genotype method was high (r = 0.513) in 178 expressed apo(a) alleles. This nomenclature is achieved by using standard serum of kringle IV repeats. We conclude that this method is an approach to genotyping to designate the phenotypes by kringle IV repeats.
Mutagenicity of 15 nitrated polycyclic aromatic hydrocarbons (nitro PAHs), which were detected in ambient air particles and/or combustion source emissions, were examined using a set of six Salmonella typhimurium tester strains (TA7001 to TA7006), and the mutational specificity was characterized by the comparison of the mutagenic potencies of nitro-PAHs in the tester strains. Each strain carries a unique missense mutation in the histidine operon and is reverted by only one specific base-substitution out of six possible changes. All nitro-PAHs tested were mutagenic in multiple strains, and were classified into four categories based on the strains predominantly reverted. 1-Nitropyrene (1-NPy), 2,7-dinitrofluoren-9-one and 1,3-, 1,6- and 1,8-dinitropyrene isomers exerted the highest mutagenicity in strain TA7005 (C.G-->A.T transversion) followed by strain TA7006 (C.G-->G.C transversion). 2- And 3-nitrofluoren-9-one isomers, 2-NPy and 2,7-dinitrophenanthrene were also markedly mutagenic in strain TA7005 but not in strain TA7006. For 2-, 3- and 9-nitrophenanthrene isomers, 2-nitrofluoranthene (2-NFT) and 4-NPy, TA7004 (G.C-->A.T transition) was the most responsive strain. 3-NFT was unique, showing the highest mutagenicity in strain TA7002 (T.A-->A.T transversion). All nitro-PAHs tested induced C.G-->A.T transversion, which is observed as the most frequent base-substitution mutation of p53 tumor suppressor gene in human lung cancer.
The effect of rat liver S9 on the mutagenicity of 10 nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) was evaluated with Salmonella typhimurium TA98NR using S9 from phenobarbital-, 3-methylcholanthrene (MC)-, beta-naphthoflavone- and polychlorobiphenyl-treated and untreated rats. 2-Nitrofluorene (2-NFI), 2-nitrofluoren-9-one (2-NFlone), 2-nitrocarbazole (2-NCz), 3-NCz, 2-nitrodibenzothiophene (2-NDBT), 2-nitro-6H-dibenzo[b,d]pyran-6-one (2-NDBP) and 3-NDBP were metabolically activated by one or more of the S9 fractions, and the highest enhancement of the mutagenic potency of nitro-PAHs was observed with 3-MC-induced S9. Only in the case of 3-NFlone was the mutagenicity in strain TA98NR decreased by the addition of S9, regardless of S9 induction. 2-NDBP was most efficiently activated among nitro-PAHs tested by all S9 fractions used. The cytosolic fraction of S9 accounted for more of the activation of 2-NDBP than the microsomal fraction. NADH and NADPH were the most effective electron donors on the activation of 2-NDBP by S9, 2-NDBP was also metabolically activated by NADH plus commercial preparations of xanthine oxidase. These activations of 2-NDBP were inhibited by allopurinol, indicating that cytosolic xanthine oxidase in rat liver S9 participates in the activation of 2-NDBP. The potency of 2- and 3-NDBP isomers as base-substitution mutagens was also enhanced by S9. In the presence of S9, both compounds showed the highest mutagenicity in strain TA7005 (C.G-->A.T) followed by strains TA7004 (G.C-->A.T), TA7006 (C.G-->G.C) and TA7002 (T.A-->A.T), and this mutation specificity was similar to that without S9, indicating that the mechanism of mutagenesis caused by NDBP isomers with S9 is similar to that without S9.
The case of a 70-year-old Japanese woman with adenoid cystic carcinoma (ACC) of the esophagus is presented herein. The patient presented with progressive dysphagia, and an upper gastrointestinal series and esophagogastroscopy revealed a protruding tumor located in the middle portion of the esophagus. Ultrasonography (US) and computed tomography (CT) suggested a lymph node metastasis between the left lobe of the liver and the esophagocardiac junction. Histopathologic examination of a biopsy specimen showed squamous cell carcinoma (SCC) and a subtotal esophagectomy was performed under the preoperative diagnosis of esophageal carcinoma. However, the histopathologic diagnosis of the resected specimen proved to be ACC of the esophagus with a lymph node metastasis around the left gastric artery. We report the clinicopathological findings of this case and briefly discuss the clinical implications of ACC.
The seroprevalence of Helicobacter pylori in a group of 1,043 healthy Japanese people was compared with that of hepatitis A virus (HAV), which was used as a marker of fecal-oral exposure. No statistically significant relationship was observed between seropositivity for HAV and that for H. pylori. Therefore, the fecal-oral spread of H. pylori is of limited relevance in Japan.
To investigate the pathogenicity of the hyphal form of Candida in pyelonephritis a Candida albicans strain, assuming only the yeast form but not the hyphal form when induced by ultraviolet mutagenesis, and a revertant strain from this mutant strain showing bimorphism were compared in a rat experimental model with regard to the incidence of ascending Candida pyelonephritis and the grade of inflammation. To increase the frequency of pyelonephritis unilateral incomplete ureteral stenosis was created. The revertant strain assuming the hyphal form showed a significantly (p < 0.01) higher frequency of pyelonephritis as compared with the mutant strain not assuming this form, and the grade of inflammation was also higher in the revertant strain group. Also, higher renal tissue and serum levels of both lipid peroxide and superoxide dismutase, which are related to marked renal oxidant injury, tended to be correlated with the degree of neutrophil infiltration in the acute phase. These findings suggest that the hyphal form plays an important role in the development of C. albicans pyelonephritis and also that the oxygen radicals from neutrophils appearing at the sites of inflammation play a major part in the further extension of inflammatory lesions.
There are three group I introns in the nuclear small subunit ribosomal RNA gene (SSU rDNA) of the ballistoconidiogenous anamorphic yeast-like fungus Tilletiopsis flava JCM 5186. The size of these sequences were 325 nt (position 516), 335 nt (position 1199) and 437 nt (position 1506), respectively. The introns at position 516 (T.flav516) and position 1199 (T.flav1199) belonged to subgroup IB3, and that of position 1506 (T.flav1506) belonged to subgroup IC1. The results of comparison with other group I introns found in SSU rDNA of eucaryotes showed that the positions 516 and 1199 were common positions to IB3 group I introns of fungi and green algae, and that positions 943, 1506 and 1512 were those to IC1 group I introns of fungi, and green and red algae. It is indicated that the insertion position of introns have close relationship with the nature of the subgroup to which they belonged. For phylogenetic analysis, we employed 9 IB3 introns, in which 7 were at position 516 and 2 were at position 1199, and 25 IC1 introns. The maximum likelihood tree based on the conserved region alignment showed that group I introns of subgroup IB3 were phylogenetically distant from those of subgroup IC1. T.flav516 (basidiomycete) constituted a subcluster with R.dacr516 (basidiomycete) and M.albo516 (ascomycete). T. flav1199 was located at the closer position of C.chlo1199 (green alga) than other IB3 introns at position 516. T.flav1506 was located at the subcluster, which was constituted by the 1506 introns found in SSU rDNA of fungi (B.yama1506, P.cari1506, and P.inou1506) and those of green algae (C.elli1506, C.mira1506, G.spir1506, and M.sacl1506) with IC1 introns at the position 1512 (D.parv1512 and C.sacc1512). The analysis of flanking regions showed that both 5' and 3' flanking sequences were well conserved in each insertion site, and indicated that the ancestors of the intron at different site had been inherited from the different origin. Therefore, the two IB3 introns found positions 516 and 1199, T.flav516 and T.flav1199, were supposed to have the independent ancestors. Our results supported the theory of the diversity of group I introns that group I introns had been transferred horizontally to the distinct insertion site, and were inherited and diverged vertically.
BACKGROUND: The clinical course of patients with carcinoma of the gallbladder depends on the depth of tumour invasion. This study was conducted to clarify the prognostic factors affecting survival and appropriate surgical strategy based on depth of invasion of gallbladder carcinoma according to the pathological tumour node metastasis (pTNM) classification. METHODS: A total of 70 patients who underwent surgical resection were reviewed retrospectively with regard to the type of operation, histopathological findings of the resected gallbladder carcinoma and clinical follow-up after operation. RESULTS: Twelve patients with pT1 gallbladder carcinoma fared favourably following cholecystectomy or extended cholecystectomy. In 13 of 26 patients with pT2 gallbladder carcinoma, lymph node metastasis was evident: pN1 in eight and pN2 in five. The 3-year survival rate of patients with pT2 gallbladder carcinoma was 28 per cent after cholecystectomy, 91 per cent after extended cholecystectomy and 67 per cent after hepatectomy. In 21 of 28 patients with pT3 or pT4 gallbladder carcinoma, surgical margins were affected by malignant cells. The 1-year survival rate of patients with pT3 or pT4 gallbladder carcinoma was 24 per cent, even after hepatectomy. Significant prognostic factors were age, macroscopic type, histological grade, depth of invasion, lymph node metastasis, pathological stage, lymphatic invasion, venous invasion, perineural invasion and involved surgical margins. CONCLUSION: Cholecystectomy was adequate for pT1 gallbladder carcinoma. Extended cholecystectomy or hepatectomy with extrahepatic bile duct resection and lymph node dissection (pN1 and pN2) were justified for pT2 gallbladder carcinoma. The survival of patients with more advanced gallbladder carcinoma remains dismal.
We investigated the effects of chronic treatment with food containing one of five antidepressants on substance P (SP) content in the rat brain using radioimmunoassay and enzyme-immunoassay. The antidepressants used were imipramine, desipramine, clomipramine, amoxapine and mianserin. Following 40 days of treatment, all the antidepressants decreased SP concentrations in the striatum, substantia nigra and amygdala. Only imipramine and desipramine reduced the peptide content in the hippocampus, and only mianserin reduced it in the septum. We further examined the acute effects of antidepressants one hour after a single intraperitoneal administration. Acute imipramine and desipramine treatment reduced SP in the striatum, whereas acute mianserin decreased it in the striatum and substantia nigra. These results demonstrate that all antidepressants on chronic treatment had a common effect, a reduction of SP content in the striatum, substantia nigra and amygdala. This raises the possibility that such a decrease may contribute to the therapeutic action of antidepressants in affective disorders.
Rat mast cell tryptase was purified to homogeneity from rat tongue by a series of standard chromatographic procedures. Since the enzyme gave band corresponding to molecular mass of 32-35 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis and exhibited a molecular mass of 135 kDa on gel filtration, it was presumed to be a noncovalently associated tetramer. The N-terminal amino acid sequence of 50 residues of the enzyme showed the highest degree of homology with the same region in mouse mast cell protease 7 (92%), and less homology to those of tryptases from man and dog, and peritoneal cells of rats and Mongolian gerbils. The inhibitor specificity of rat tongue tryptase was similar to that of rat peritoneal mast cell tryptase free from trypstatin: it was inhibited by alpha 1-antitrypsin, Kunitz-type soybean trypsin inhibitor and Bowman-Birk soybean trypsin inhibitor, but these inhibitors do not inhibit the tryptases from rat skin, human lung, and dog mast cells. Judging from these results, together with other enzymatic properties, the enzyme may be a novel isoform of tryptase in rat tongue. Analysis by differential staining with peroxidase-labeled lectins of the enzyme suggested that it has tri- and/or tetraantennary complex-type oligosaccharides containing a relatively high amount of sialic acid. The immunohistochemical distribution of this enzyme indicated that the reactive antigen was specific in connective tissue but not in mucosal mast cells.
We describe a case of varicella pneumonia in a 24-year-old healthy man presenting with severe respiratory failure. A chest radiograph showed diffuse, bilateral airspace consolidation; additional complications included liver dysfunction and thrombocytopenia. However, treatment with intravenous acyclovir and gamma-globulin improved his clinical symptoms and signs. A greater than four-fold change in paired titers of the varicella-zoster virus antibody was observed. Bronchoalveolar lavage performed during the recovery phase revealed increased total cell and lymphocyte counts and a decreased CD4:CD8 ratio of T lymphocytes. Transbronchial lung biopsy findings were compatible with a diagnosis of interstitial pneumonia.