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Biomedical subjects

H Amemiya

Publications and source records attributed to H Amemiya.

At least 37 records · Page 2Linked to original sources
PubMed2000

Inhibition of Fas-mediated fulminant hepatitis in CrmA gene-transfected mice.

Hyperimmune response via Fas/Fas-ligand and perforin/granzyme pathways may be essential in pathogenesis of virus-induced fulminant hepatitis. CrmA inhibits activation of caspases and granzyme B, suggesting it may block these pathways. We investigated whether CrmA expression would inhibit Fas-associated lethal hepatitis in mice. We successfully generated AxCALNLCrmA, a recombinant adenovirus expressing CrmA gene with a Cre-mediated switching cassette. We increased CrmA expression level in the liver transfected with AxCALNLCrmA (10(9) pfu) by increasing administration dose (10(7)-10(9) pfu) of AxCANCre, a recombinant, adenovirus-expressing Cre gene. Injection of anti-Fas antibody into the control mice rapidly led to animal death due to massive liver apoptosis, while the apoptosis was dramatically reduced in the CrmA-expressed mice. The animal survival increased with an increase of CrmA expression. The formation of active caspase-3 was markedly inhibited in the crmA-transfected hepatocytes in vitro. These results suggest that crmA is an effective gene that can inhibit immune-related liver apoptosis.

Adenoviridae↗
PubMed2000

Immunosuppressive therapy using FTY720 combined with tacrolimus in rat liver transplantation.

BACKGROUND: FTY720 (FTY) exerts its effects through a reduction of peripheral lymphocytes. This unique mechanism allows for a possible combination effect with other immunosuppressants. We investigated therapy with FTY combined with tacrolimus (FK) in rat liver transplantation. METHODS: Different doses of FK, FTY, or both were orally administered to the recipients for 15 days. Expression of cytokine mRNAs using RT-PCR and appearance of lymphocyte apoptosis by immunohistologic staining were studied in the allografts. RESULTS: Recipients treated with a low dose of FK (0.3 mg/kg) or FTY (0.03 mg/kg) showed a slightly prolonged survival time, although combination therapy with these drugs prolonged survival time similar to the duration obtained by an optimal dose of each drug alone. A marked suppression of lymphocyte infiltration and decreased levels of mRNAs for IL-2, IFN-gamma, and granzyme B were seen in the grafts with combination therapy. Grafts with combination therapy showed an increased number of cells double-stained with TUNEL and CD2 in infiltrated lymphocytes. CONCLUSIONS: Allografts that underwent combination therapy demonstrated markedly reduced lymphocyte infiltration; a number of cells had induced apoptosis and an inhibition of IL-2, IFN-gamma, and granzyme B mRNA transcription, but not IL-4 and IL-10 transcripts, accounting for powerful mutual effect of FTY and FK.

Animals↗
PubMed2000

High frequency of c-Met expression in gastric cancers producing alpha- fetoprotein.

Gastric cancers producing alpha-fetoprotein (AFP) have a poor prognosis and a high incidence of liver metastasis. Hepatocyte growth factor (HGF) and its receptor, c-Met, are known to induce mitosis and cell movement and to promote tumor progression. In the present study, c-Met and HGF expression in AFP-producing gastric cancer was compared with those gastric cancers that do not produce AFP. Twenty-six patients with AFP-producing gastric cancers [AFP(+)] and 26 patients stage-matched gastric cancers without AFP production [AFP(-)] were evaluated for c-Met and HGF expression and proliferating cell nuclear antigen-labelling index using immunohistochemical analysis. A higher frequency of c-Met expression was observed in the AFP(+) group than in the AFP(-) group (p < 0.01). A higher expression of c-Met might be one explanation for the poorer prognosis of AFP-producing gastric cancers.

Adult↗
PubMed2000

A peculiar form of focal atrial tachycardia mimicking atypical atrial flutter.

A 55-year-old man was referred because of congestive heart failure and atrial flutter. A 12-lead electrocardiogram (ECG) showed positive P waves in leads II, III, and aVF with a continuously undulating pattern that lacked an isoelectric baseline. Tachycardia was diagnosed as atypical atrial flutter based on classical criteria. An electrophysiological study and catheter ablation using an electroanatomical system revealed the mechanism of the tachycardia to be focal atrial tachycardia originating from the left atrial roof. This case indicates that focal atrial tachycardia may present as atypical atrial flutter on the surface ECG.

Atrial Flutter↗
PubMed1999

Prolonged cardiac allograft survival in rats systemically injected adenoviral vectors containing CTLA4Ig-gene.

BACKGROUND: CTLA4Ig, a soluble recombinant fusion protein that contains the extracellular domain of the CTLA4 and Fc portion of IgG1, strongly adheres to the B7 molecule to block CD28-mediated costimulatory signals and inhibits in vitro and in vivo immune responses. In vivo gene transfer using adenovirus vector achieves a high transfection rate into organ cells that usually contain adenoviral receptors. In this study, we investigated expression levels of the transfected gene and the survival times of the allografts in cardiac recipients systemically administered adenoviral vectors containing CTLA4Ig. METHODS: Hearts from DA rats (RT-1a) were transplanted into a cervical location in LEW recipients (RT1(1)). The adenoviral vectors containing CTLA4Ig was injected via a recipient vein immediately after grafting. RESULTS: The serum level of CTLA4Ig reached to maximum at 51-93 microg/ml 3 to 7 days after gene-transfection and declined after 14 days, although detectable levels were observed up to 49 days. The median survival time of the allografts in the gene-transfected group were significantly prolonged (27 days) in compared to the control group (6 days). In addition, down-regulation of IL-2 and IFN-gamma mRNAs and persistence of IL-4 and IL-10 transcripts were observed in the graft infiltrating cells. CONCLUSION: The adenovirous-mediated CTLA4Ig gene transfer into a recipient liver by systemic administration resulted in remarkable prolongation of cardiac allograft survival. Its action mechanisms may be mediated by inhibition of CD28-associated signal transduction, reduction of Th1-type cytokine production, and continuous expression of Th2-type cytokines in the activating lymphocytes.

Abatacept↗
PubMed1999

T-cell dysfunction in a patient with short bowel syndrome: report of a case.

We describe herein the case of a 48-year-old man who underwent emergency massive resection of the small intestine due to strangulated ileus, which led to short bowel syndrome (SBS) as he was left with 7 cm of jejunum and 8 cm of ileum. We evaluated the immune function in this patient, focusing particular attention on T-cell-mediated immunity. Biochemical and nutritional parameters, including minerals and trace elements, indicated that the patient was in relatively good health; however, the proliferative response to mitogen and tumor necrosis factor-alpha production in response to the anti-CD3 monoclonal antibody in peripheral blood lymphocytes (PBL) were impaired compared with age-matched postgastrectomy patients and healthy donors. Moreover, the expression of T-cell receptor (TCR) zeta, which is involved in signal transduction and the subsequent activation of T cells, was downregulated in this patient compared with that in the age-matched postgastrectomy patients and healthy donors. These observations suggest that T-cell function was disturbed in our patient, and that this dysfunction was associated with the decreased expression of TCR zeta molecules.

Complement System Proteins↗