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H Sugaya

Publications and source records attributed to H Sugaya.

At least 37 records · Page 2Linked to original sources

Analysis of T cell populations and IL-3 mRNA expression in mesenteric lymph node cells and intestinal intraepithelial lymphocytes in Strongyloides ratti-infected mice.

T cell populations and IL-3 mRNA expression were analysed in mesenteric lymph node cells and intestinal intraepithelial lymphocytes (IEL) in Strongyloides ratti-infected mice. On days 7 and 12 post-infection, 2.6 times as many mesenteric lymph node cells were present in S. ratti-infected mice compared with uninfected mice. Although the percentages of CD3+, CD4+ and CD8+ cells decreased during infection, the absolute numbers of these cell types increased on day 7 due to an overall increase in the mesenteric lymph node cell number. The CD4/CD8 ratio in IEL was increased on day 5, whereas no significant change in the CD4/CD8 ratio was observed in the mesenteric lymph node cells. Expression of IL-3 mRNA, which is an important cytokine for the induction of murine mucosal mastocytosis and S. ratti-expulsion, was examined in mesenteric lymph nodes and IEL of uninfected and infected mice. IL-3 mRNA was detected in mesenteric lymph nodes of S. ratti-infected mice but not detected in the lymph nodes of uninfected mice. IL-3 mRNA was detected in IEL from both infected and uninfected mice with an 20-fold increase in expression in IEL of infected mice. Overall, IL-3 mRNA levels were higher in IEL than in mesenteric lymph nodes following S. ratti-infection. Expression of IL-4, IL-10, stem cell factor (SCF or c-kit ligand) and IFN-gamma mRNA was also examined in these two tissues. IL-10 mRNA was not detected in any tissue examined and IFN-gamma mRNA levels were unaltered as a result of an S. ratti-infection. Elevated expression of mRNA for SCF (5-fold) and IL-4 (20-fold) was observed in the mesenteric lymph nodes of infected mice. In contrast, SCF mRNA levels were similar in IEL of uninfected and infected animals and only a modest increase in IL-4 mRNA was observed in IEL of infected mice.

Animals↗

A case of late onset primary hyperoxaluria type I (PH-I) presented with black liver.

A 63-year-old woman who had received hemodialysis therapy since she fell acute on chronic renal failure 4 years ago presented with multiple joint pain. Nephrocalcinosis was not detected by abdominal X-ray when hemodialysis therapy was initiated. Laboratory testing showed azotemia, anemia, hypoproteinemia and mild liver dysfunction but no liver cirrhosis. Biopsied bone tissue demonstrated numerous calcium oxalate crystal depositions. Laparoscopy revealed black liver in macroscopic view. Histological studies showed numerous lipofuscin-like dark brown granules were deposited in hepatocytes. The activity of alanine : glyoxylate aminotransferase (AGT) was less than 0.1 U/g in biopsied patient's liver tissue. Generally, clinical symptoms demonstrated by Japanese primary hyperoxaluria type I (PH-I) patients are milder than those of European patients. Some PH-I patients may successfully avoid urinary tract calcification unless they fall into oliguria by some other causes. The lipofuscin granules are most likely the source of the dark color. Massive deposition of the lipofuscin granules indicated that the duration of the liver metabolic abnormality had lasted for long time. Thus, black liver may be related to a mild form of PH-I.

Biopsy↗

Cytokine responses in mice infected with Angiostrongylus cantonensis.

For determination of the kinetics of cytokine production and its possible role in host resistance to Angiostrongylus cantonensis in the mouse, Th1 [interleukin 2 (IL-2) and interferon gamma (IFN-gamma] and Th2 (IL-5 and IL-4) cytokine production in the cerebrospinal fluid (CSF), sera, and culture supernatants of spleen cells (SC) or cervical lymph-node cells (CLNC) of infected BALB/c and C57BL/6 mice was assessed by a sandwich enzyme-linked immunosorbent assay (ELISA). IL-5 and IL-4 were detected in CSF of both strains, with a peak response occurring at around days 12-15 and 20 postinfection (p.i.), respectively. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay also revealed prominent IL-5 and IL-4 mRNA expression in T-cells but not in eosinophils in CSF. SC and CLNC stimulated with A. cantonensis young adult-worm antigen released IL-5 in vitro at and after day 20 p.i. Contrarily, IFN-gamma production in CSF and SC or CLNC culture supernatants was almost negligible before day 30 p.i. IL-5, IL-4, and IL-2 production in culture supernatants was rather prominent in resistant C57BL/6 mice as opposed to susceptible BALB/c mice as assessed by the magnitude of increase over preinfection levels. Antigen-specific IgG1 (but not IgG2a) responses were more prominent in C57BL/6 mice than in BALB/c mice. These data suggest that systemic and local Th2 cytokine responses, especially those involving IL-5, are predominant in A. cantonensis-infected mice and that IL-5 is an important cytokine underlying the innate resistance of the mouse against A. cantonensis.

Angiostrongylus cantonensis↗

Eosinophilia and intracranial worm recovery in interleukin-5 transgenic and interleukin-5 receptor alpha chain-knockout mice infected with Angiostrongylus cantonensis.

We infected interleukin-5 (IL-5)-transgenic (IL-5-Tg) and IL-5 receptor alpha knockout (IL-5R alpha -/-) mice with Angiostrongylus cantonensis to determine the possible roles of IL-5 and eosinophils in A. cantonensis infection in mice. IL-5-Tg mice demonstrated significantly higher eosinophilia in bone marrow, blood and cerebrospinal fluid (CSF), lower intracranial worm recovery and smaller female worms than naive C3H/HeN mice. Both IL-5-Tg and C3H/HeN mice evoked antigen-specific serum and CSF IgA antibody responses as early as days 5 and 7 postinfection, respectively. Prominent eosinophil infiltration was noted around intracranial worms in the subarachnoid spaces of the mouse brains; eosinophils adhering to the worm surface were degranulated. In contrast, IL-5R alpha -/- mice yielded a higher worm recovery than wild-type or heterozygous mice at day 20 postinfection and failed to provoke CSF eosinophilia. These findings indicate that A. cantonensis infection in the mouse causes IL-5 production and subsequent CSF eosinophilia, the latter probably being involved in the killing of intracranial worms.

Angiostrongylus cantonensis↗

Induction of cerebrospinal fluid eosinophilia in rats by the intraventricular injection of Angiostrongylus cantonensis antigen.

Resistance to Angiostrongylus cantonensis is contingent upon the generation of an eosinophilic response in the CSF of infected hosts. We have studied the parameters required for the generation of this CSF eosinophilia in normally permissive rats. We initially induced a marked peripheral eosinophilia in rats by infection with either Mesocestoides corti or Angiostrongylus cantonensis or the surgical transfer of A. cantonensis young adult worms (YA) into their pulmonary arteries. Next, we injected various antigens into the ventricles of these rats. A. cantonensis-preinfected rats demonstrated significant CSF eosinophilia following injection of A. cantonensis egg antigen, 1st-stage larval (L1) antigen, or M. corti antigen, but not following YA antigen inoculation. A. cantonensis egg and M. corti antigens were potent chemoattractants for eosinophils in an in vitro chemotaxis assay. These data indicate that peripheral eosinophilia, meningeal stimulation by A. cantonensis infection and the presence of potent chemoattractants, e.g., egg and L1 antigens are prerequisites for CSF eosinophil accumulation in permissive rat hosts.

Angiostrongylus cantonensis↗

Mediastinal lymph node cells of Angiostrongylus cantonensis-infected rats respond to antigens and release interleukin-5 in vitro.

The kinetics of eosinophil growth and/or survival stimulating factor (Eo-stimulating factor) production in Angiostrongylus cantonensis-infected rats was assessed by in vitro marrow cultures. When lymphocytes, obtained from cervical, mediastinal or mesenteric lymph nodes of infected WKAH rats, were cultured with A. cantonensis antigens, Eo-stimulating factor activity was detected in the conditioned media obtained only from mediastinal lymph node cells at and after 35 days p.i. Eo-stimulating factor activity in the conditioned media was not detected before or at 20 days p.i. The kinetics of the factor was, therefore, almost identical to those of eosinophilia in bone marrow and peripheral blood. This Eo-stimulating factor activity was inhibited (maximum inhibition = 73%) by anti-mouse IL-5 monoclonal antibody in a dose-dependent fashion, indicating that the factor would be, at least in part, identical to IL-5. Similar Eo-stimulating factors were also detected in the conditioned media which were obtained by stimulating spleen cells from Wistar rats at 35-45 days p.i. with Con A. These data suggest that lymphocytes in the mediastinal lymph nodes, local lymph nodes near the adult worm habitat, could play an essential role in induction of eosinophilia in A. cantonensis-infected rats.

Angiostrongylus cantonensis↗

Defective B-1 cell development and impaired immunity against Angiostrongylus cantonensis in IL-5R alpha-deficient mice.

We generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting. The IL-5R alpha-/- mice showed decreased numbers of B-1 cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B cell responses to T-independent antigens. The number of alpha beta T cell receptor-positive thymocytes tended to decrease in 3-week-old IL-5R alpha-/- mice, returning to normal by 6 weeks of age. The IL-5R alpha-/- mice produced basal levels of eosinophils, while their bone marrow cells failed to form eosinophilic colonies in response to IL-5. Impaired eosinophilopoiesis in IL-5R alpha-/-mice enhanced the survival of Angiostrongylus cantonensis. These results indicate that IL-5-induced eosinophils serve as potent effector cells in the killing of Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis↗

[Glucose intolerance after percutaneous ethanol injection therapy (PEI) in liver cirrhosis patients with hepatocellular carcinoma].

We studied the effect of percutaneous ethanol injection therapy (PEI) on glucose tolerance in liver cirrhosis patients with hepatocellular carcinoma. All of 10 patients underwent PEI and aspiration biopsy of the tumor on separate day. Two-time oral glucose tolerance tests (OGTT), before and after PEI, were performed in all patients. There were no significant changes in blood glucose and insulin chronologically measured on aspiration biopsy and PEI. To detect changes in glucose tolerance, we compared the results of OGTT before PEI with those of OGTT after PEI. On the basis of results of OGTT before PEI, patients were classified to impaired glucose tolerance group (4) and diabetes mellitus group (6). Blood glucose at 180 minutes on OGTT after PEI showed significantly higher value than that of OGTT before PEI, but insulin response was not suppressed. From these experiments we speculate that exaggerated insulin resistance due to injected ethanol may be one of the factors influencing glucose tolerance after PEI.

Aged↗

The role of eosinophils in Angiostrongylus cantonensis infection.

Angiostrongylus cantonensis is the causative agent of human eosinophilic meningoencephalitis in the Pacific Islands and Southeast Asia. Prominent eosinophilia in the cerebrospinal fluid (CSF) of the patients has been used as one of the diagnostic criteria for the disease but the role(s) of the CSF eosinophils has remained to be elucidated. In this article, Kentaro Yoshimura, Hiroko Sugaya and Kazuto Ishido discuss the involvement of CSF eosinophils in the killing of intracranial worms and the damage of the central nervous system of the hosts, and consider why eosinophils in A. cantonensis infection play a more important role in nonpermissive hosts (including humans) than in the permissive rat host.

Journal Article↗