T. Shimizu

Aichi Medical University, Nagoya, Aichi, Japan

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Publications (6)47.05 Total impact

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    ABSTRACT: Although mucosal alpha- and beta-chemokines are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastritis, little is known how these chemokines are related to the ulcerogenesis in peptic ulcer patients. We examined the levels of interleukin (IL)-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures and the numbers of inflammatory cells infiltrating the lamina propria by using the mucosal tissues obtained from gastric ulcer (GU) patients with and without H. pylori infection. Levels of IL-8 and MIP-1alpha secreted in organ cultures were measured by an enzyme-linked immunosorbent assay. Numbers of myeloperoxidase-positive neutrophils, CD68-positive macrophages, and mononuclear cells were determined in tissue sections. The mucosal tissues of both the gastric antrum and the ulcer site obtained from patients with H. pylori-positive GU showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of inflammatory cells compared with the corresponding mucosal tissues from those with H. pylori-negative GU or the antral mucosal tissues from H. pylori-negative controls. When the values were compared between the mucosal tissues from the gastric antrum and those from the ulcer site, the latter group of tissues showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of neutrophils and macrophages than the former group regardless of its healing process in patients with H. pylori-positive GU. Mucosal alpha- and beta-chemokines may be important to the ulcerogenesis in H. pylori-associated GU disease.
    Digestion 02/2000; 62(2-3):87-94. · 1.94 Impact Factor
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    ABSTRACT: Mucosal chemokines are considered to be important in the pathogenesis of Helicobacter pylori-associated gastritis. The aims of this study are to examine the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures, the expression of MIP-1alpha mRNA and the cellular source of MIP-1alpha, using the antral mucosal specimens obtained from H. pylori-positive and -negative patients. Enzyme-linked immunosorbent assay was used to measure the levels of MIP-1alpha in organ cultures of mucosal tissues and cell cultures of fractionated mucosal cells. The expression of MIP-1alpha mRNA and protein was analysed in fresh biopsy tissues with reverse transcriptase-polymerase chain reaction (RT-PCR) and double immunofluorescence microscopy, respectively. The mucosal specimens obtained from H. pylori-positive patients exhibited significantly higher values of MIP-1alpha activity in organ cultures with increased numbers of CD68+ macrophages, myeloperoxidase+ neutrophils and mononuclear cells in the lamina propria compared with those from H. pylori-negative patients. The RT-PCR analysis detected MIP-1alpha mRNA in more than 50% of the specimens with H. pylori infection, but not in those without infection. In cell cultures, the macrophage fraction contained substantially higher amounts of MIP-1alpha on a per cell basis than the lymphocyte fraction and MIP-1alpha activity was not detected in cultures of gastric epithelial cells. This observation was also confirmed by a double immunofluorescence microscopic study in which most (>90%) MIP-1alpha-positive infiltrating cells were CD68+ macrophages. This study indicates that synthesis and secretion of MIP-1alpha are increased in H. pylori-infected antral mucosa and that mucosal macrophages are the main cell type responsible for this phenomenon.
    Journal of Gastroenterology and Hepatology 02/1999; 14(1):20-6. · 3.33 Impact Factor
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    ABSTRACT: Tissue accumulation of polymorphonuclear neutrophils (PMN) in Inflammatory Bowel disease (IBD) might be, in part, due to a delay in apoptotic processes associated with the effects of their specific growth factors and inflammatory cytokines. We addressed this hypothesis by examining the activity of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) in the organ culture supernatants of colonic mucosal specimens and their regulatory effects on PMN apoptosis in patients with IBD. The contents of G-CSF and GM-CSF in the supernatants were measured by the enzyme-linked immunosorbent assays and PMN apoptosis was evaluated by acridine orange/ethidium bromide staining, respectively. Mucosal specimens obtained from patients with active IBD exhibited higher levels of G-CSF and GM-CSF activity than controls. Notably, the levels of G-CSF activity were approximately 1000-fold higher than those of GM-CSF activity. Freshly isolated PMN showed a time-related increase in the proportion of cells with characteristic features of apoptosis when they were incubated with the culture medium alone and exposure of PMN to recombinant G-CSF and GM-CSF caused a concentration-dependent inhibition of apoptosis. Incubation of PMN with the supernatants from patients with active IBD induced an inhibitory effect on PMN apoptosis; this effect was abrogated to a significant degree by pre-incubation of the supernatants with anti-G-CSF serum. This study suggests that PMN apoptosis may be delayed under the influence of soluble mediators, especially G-CSF, in the microenvironment of IBD-affected mucosa, thus providing possible mechanisms for tissue accumulation of PMN in IBD.
    Journal of Gastroenterology and Hepatology 02/1999; 14(1):46-53. · 3.33 Impact Factor
  • Gastroenterology 01/1998; 114. · 12.82 Impact Factor
  • Gastroenterology 01/1998; 114. · 12.82 Impact Factor
  • Gastroenterology 01/1995; 108(4). · 12.82 Impact Factor

Publication Stats

65 Citations
47.05 Total Impact Points

Institutions

  • 1999
    • Aichi Medical University
      • Division of Internal Medicine
      Nagoya, Aichi, Japan