Biomedical subjects

S Yasuda

Publications and source records attributed to S Yasuda.

At least 19 recordsLinked to original sources

PubMed1998

Nonpeptide angiotensin II receptor antagonist recognizes inter-species differences in angiotensin AT1 receptors.

Oral administration of the angiotensin AT1 receptor antagonist 3-methyl-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl ]methoxy] pyridine (ME3221) inhibited the pressor response to angiotensin II at doses of 0.3-1.0 mg/kg in rats. A higher dose of ME3221 (3-10 mg/kg) was required to obtain the same inhibitory potency in dogs. The antagonistic potency of ME3221 for angiotensin II-induced contraction in the rabbit aorta (pA2 = 8.82) was about five times higher than that in the canine aorta (pA2 = 8.18). The inhibition constant of ME3221 for displacing [125I]angiotensin II binding to membrane fractions from the rabbit aorta (Ki = 3.84 nM) and rat liver (Ki = 2.55 nM) was significantly lower than that for the canine aorta (Ki = 84.5 nM), canine liver (Ki = 122 nM) and bovine adrenal cortex (Ki = 21.5 nM). In contrast, [Sar1, Ala8]angiotensin II had a similar inhibition constant (Ki = 0.85-4.67 nM) in the species investigated. Treatment with 5 mM dithiothreitol significantly (P < 0.01) reduced the angiotensin II-induced contractile response to 1.2% in the rabbit aorta, but it did not significantly reduce the response in the canine aorta (83.2%). Dithiothreitol reduced [125I]angiotensin II binding to membrane fractions from the rabbit aorta and the rat liver but partially inhibited binding in preparations that had a low affinity for ME3221. These data indicate a species difference in the angiotensin AT1 receptor: the canine and bovine angiotensin AT1 receptor has a relatively low affinity for ME3221 and is slightly resistant to dithiothreitol. The species difference in the angiotensin AT1 receptor reflects the in vivo efficacy of ME3221 in rats and dogs.

Angiotensin Receptor Antagonists↗

PubMed1998

Fas/FasL interaction is not involved in apoptosis of activated CD4+ T cells upon HIV-1 infection in vitro.

In HIV-1-infected individuals, Fas expression and Fas/FasL-mediated apoptosis of mature T cells are known to increase compared with those in normal individuals. To elucidate a relation between acute HIV-1 infection and the regulation of Fas/FasL system upon T-cell activation, resting CD4+ T cells were acutely infected or uninfected with HIV-1 and subsequently activated by phorbol myristate acetate and ionomycin (PMA/IM). Four days after infection, when HIV-1 env gp120 is expressed in more than one half of activated T cells, Fas/FasL expression was analyzed by flow cytometry, and apoptosis-inducing activity of these activated primary CD4+ T cells on Fas+ Jurkat cells was examined. The level of Fas or FasL expression was not altered during acute HIV-1 infection. The enhanced apoptosis-inducing activity upon HIV-1 infection was observed in some individuals, but its activity was not Fas/FasL-mediated. These results indicate that HIV-1 infection is not necessarily associated with either upregulation of Fas/FasL expression or Fas/FasL-mediated apoptosis.

Antibodies, Monoclonal↗

PubMed1998

NMDA receptors in the inferior colliculus are critically involved in audiogenic seizures in the adult rats with neonatal hypothyroidism.

The effects of N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists were compared on audiogenic seizures in the rats neonatally exposed to propylthiouracil (PTU). The rats treated with 0.02% PTU through mother's milk during days 0-19 after delivery showed a high incidence of audiogenic seizures consisting of running fit (RF) followed by generalized tonic-clonic seizure (GTCS) after matured. The systemic administration with MK-801, a NMDA receptor antagonist dose-dependently inhibited both RF and GTCS. NBQX (6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione), a non-NMDA receptor antagonist, when systemically administered, failed to block audiogenic seizures. Audiogenic seizures caused a marked induction of c-fos messenger RNA (mRNA) in septal nucleus, bed nucleus of stria terminalis, amygdaloid nuclei, peripeduncular nucleus, and inferior colliculus, which was almost completely blocked by the pretreatment with MK-801. Bilateral microinjection of MK-801 into the inferior colliculus showed a tendency for inhibiting GTCS, but not RF, whereas CPP (3-(R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid), a competitive NMDA receptor antagonist produced a significant inhibition against both RF and GTCS. These NMDA receptor antagonists administered into cisterna ambience, the floor of which is composed of inferior colliculus and neighboring structures, have shown potent blocking effects on both RF and GTCS. The present results suggest that NMDA receptors in the inferior colliculus, presumably in the subnucleus of external cortex may play the critical role in the initiation of audiogenic seizures in PTU-treated rats.

Acoustic Stimulation↗

PubMed1998

Four cases of Warthin's tumor of the parotid gland detected with FDG PET.

In the cancer screening with FDG PET for 1,872 medical health club members, high FDG accumulation in the parotid gland was found in four males (age, 57-70 years). Warthin's tumor was confirmed by surgical pathology. The exact mechanism of high FDG accumulation in Warthin's tumor is not yet known. This tumor may be found incidentally during FDG PET studies. When high FDG accumulation is found in the parotid gland, integrated consideration of the results of the physical examination, medical history and 99mTc-pertechnetate scintigraphy makes it possible to differentiate Warthin's tumor from other lesions.

Adenolymphoma↗

PubMed1998

Accumulation of IL-12-activated antitumor effector cells into lymph nodes of tumor-bearing mice.

Simultaneous administration of high dose of IL-12 into tumor-inoculated mice resulted in a marked reduction of tumor growth in parallel with the augmented generation of cytotoxic T-cells, natural killer (NK) cells and IFN-gamma-producing Th cells. We found that these IL-12-activated antitumor effector cells preferentially accumulated in peripheral lymph nodes concomitantly with lymphadenopathy. However, IL-12 rather induced disappearance of antitumor effector cells including CD4+ T, CD8+ T and NK cells from spleen in spite of inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16F0-bearing mice showed a marked IFN-gamma production in response to not only IL-2, IL-12, anti CD3 mAb but also B16F0 melanoma cells. Moreover, they could lyse B16F0 melanoma cells in a long-term cytotoxicity assay. It was also confirmed that IL-12-activated IFN-gamma producing Th1 cells were accumulated in tumor local site. Thus, IL-12 appeared to have a capability of stimulating selective migration of antitumor cells into lymph nodes and tumor local sites.

Animals↗

PubMed1998

Reconstitution of immune systems in RAG2-/- mice by transfer with interleukin-12-induced splenic hematopoietic progenitor cells.

The administration of a high dose of IL-12 into the mice resulted in the induction of splenomegaly. From the flow cytometry analysis of cellularity in an enlarged spleen, it was demonstrated that Thyl.2-CD45RB-c-Kit + Sca-1 + Lin- hematopoietic progenitor cells markedly increased in IL-12-administered mouse spleen compared with untreated mouse spleen. The IL-12-induced hematopoietic progenitor cells showed a greatly enhanced colony-forming activity in CFU-granulocyte/macrophage (CFU-GM), blast-forming units-erythroid (BFU-E) and CFU-spleen (CFU-S) assay. Moreover, it was initially demonstrated that the transfer of IL-12-induced splenic hematopoietic progenitor cells into immunodeficient RAG2-/- mice caused a complete reconstitution of their immune functions including T- and B-cell-mediated immunity. Thus, the evidence that IL-12 has a capability of inducing hematopoietic progenitor cells possessing stem cell-like activity in vivo, indicated another important immunomodulating activity of IL-12 in immunotherapy.

Animals↗

PubMed1998

Differential production of monoclonal antibodies to carbohydrate moiety or peptides moiety of glycoproteins by different routes of immunization.

The administration of ABO blood group active glycoproteins via the rear footpads of BALB/c mice with subsequent fusion of popliteal lymph node lymphocytes produced hybridomas differentially secreting antibodies to the peptide moiety of antigens. On the other hand, conventional intraperitoneal immunization of the same antigens and intraperitoneal boost followed by splenic lymphocyte fusion produced hybridomas differentially secreting antibodies to the carbohydrate moiety of antigens. Similar results were obtained in the production of monoclonal antibodies to erythrocyte membranes. Almost all hybridomas obtained by rear foodpad immunization secreted antibodies to the peptide moiety of erythrocyte membrane proteins, and those obtained by intraperitoneal immunization secreted antibodies to both peptide and carbohydrate moieties of erythrocyte membrane components. These results suggest the possibility of differential production of monoclonal antibodies to the carbohydrate moiety and the peptide moiety of some glycoproteins by different immunization routes.

Animals↗

PubMed1998

Primary colorectal cancers detected with PET.

Positron emission tomography (PET) using 18F-fluorodeoxyglucose can sensitively detect cancers of increased glucose metabolism. We describe three asymptomatic individuals who were found to have colorectal cancer and underwent potentially curative surgery. On the PET images, lesions were easily discernible. Our experience and the experience of others suggest that primary colorectal cancer can be detected with PET in a resectable stage. Our three cases are presented and the potential utility of PET is discussed.

Adult↗

PubMed1998