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Biomedical subjects

S Yasuda

Publications and source records attributed to S Yasuda.

At least 145 records · Page 8Linked to original sources

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↗

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↗

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↗

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↗

Detection of HIV-Gag p24-specific antibodies in sera and saliva of HIV-1-infected adults and in sera of infants born to HIV-1-infected mothers.

Secretory immunoglobulin A (IgA) is known to play an important role in the mucosal defense against a variety of pathogens. Although the role of IgA antibodies during sexual transmission of HIV is not clear, HIV-specific IgA antibodies have been detected in various mucosal secretions of HIV-infected individuals. Using a monoclonal antibody against human IgA, we established an ELISA system to detect anti-HIV p24 IgA antibodies in sera and saliva. We have analyzed the levels of anti-HIV p24 IgG and IgA antibodies in sera and saliva of 107 and 119 adults, respectively, with HIV infection at different clinical stages, and in the sera of 13 infants born to HIV-infected mothers. The level of anti-HIV p24 IgA antibodies was lower in sera and higher in saliva as compared to that of anti-HIV p24 IgG antibodies. Where the percentage of HIV-specific serum antibody-positive cases decreased with disease progression, that of saliva antibody-positive cases increased in AIDS patients. Among the 13 infants born to HIV-infected mothers, 7 infants were HIV-p24-specific serum IgA positive. These sera were negative for anti-HIV p24 secretory IgA, suggesting that some infants develop their own immune responses against HIV infection. Thus, the detection of HIV-specific IgA antibodies, especially in saliva, could be a simple and reliable test for the diagnosis of HIV infection.

AIDS Serodiagnosis↗

Chronic thyroiditis: diffuse uptake of FDG at PET.

PURPOSE: To determine the frequency and clinical importance of diffuse 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in the thyroid gland. MATERIALS AND METHODS: A total of 1,102 healthy subjects underwent whole-body positron emission tomography (PET). PET images were evaluated for increased diffuse FDG uptake in the thyroid gland. Serum free thyroxine and thyrotropin levels were measured in 36 subjects with increased uptake and in 36 matched control subjects without uptake. Antithyroid antibodies were also measured. Morphologic abnormalities were examined by using ultrasonography (US). RESULTS: Diffuse FDG uptake was found in three men and 33 women; the prevalence was significantly higher in women (P < .01). Thirty-five subjects were euthyroid; one had hypothyroidism. Antithyroid antibodies were positive in 27 subjects. In most subjects, US findings facilitated the diagnosis of chronic thyroiditis. In control subjects, the positive rates for antithyroid antibodies and US abnormalities were significantly lower than those of the study group (P < .01). CONCLUSION: Diffuse thyroidal FDG uptake may be an indicator of chronic thyroiditis. The actual prevalence of the disorder was not low in this series, and such lesions may be found incidentally at FDG PET.

Adult↗

Effects of dietary unsaturated fatty acid and chronic carbon tetrachloride treatment on the accumulation of oxidation products, alpha-tocopherol and liver injury in mice.

Mice, at weaning, were placed on a diet supplemented with beef tallow (BT), linoleic acid (18: 2n-6)-rich safflower oil (SO), alpha-linolenic acid (18: 3n-3)-rich perilla oil (PO) or docosahexaenoic acid (22: 6n-3, DHA)-rich fish oil (FO) to modify membrane fatty acid vulnerability to peroxidation, then carbon tetrachloride (CCl4) was administered chronically. CCl4-induced liver injury, estimated using serum alanine aminotransferase activity and liver hydroxyproline content, was not different among the 4 dietary groups; however, the FO diet lowered the liver triacylglycerol (TG) level when compared with the BT and SO diets. The FO diet group exhibited a significantly higher level of thiobarbituric acid-reactive substances (TBARS) in the liver when compared with the three other dietary groups. Chronic CCl4 treatment decreased the proportion of eicosanoid precursors (arachidonate and eicosapentaenoate) rather than that of DHA, with the highest peroxidizability among major fatty acids in liver, and did not enhance TBARS formation in any of the dietary groups. The protein carbonyl content in the liver was similar among the 4 dietary groups but was decreased following CCl4 treatment. Liver alpha-tocopherol contents were affected both by diet and CCl4 treatment, and a positive correlation was observed between alpha-tocopherol and TG contents. These results indicate that increasing the autoxidizability of dietary fatty acids or the chronic CCl4 treatment did not synergistically enhance liver injury or the accumulation of oxidation products in mice.

Alanine Transaminase↗

High-dose immunoglobulin G therapy for fulminant myocarditis.

The cardiac function of an adult patient with fulminant myocarditis requiring a mechanical circulatory support was improved, along with the suppressed release of inflammatory mediators, after intravenous infusion with high-dose immunoglobulin. This therapy may have immunomodulatory effects and serve as a potential adjunctive therapy for patients with fulminant myocarditis.

Adjuvants, Immunologic↗

Advanced nasopharyngeal carcinoma treated with chemotherapy and radiotherapy: distant metastasis and local recurrence.

One hundred and twenty-nine patients with NPC treated at the Department of Radiology, Chiba University Hospital and Keio University Hospital from 1980 through 1993 were selected for this study. Forty-four patients received cisplatin (CDDP)- or carboplatin-based chemotherapy, and 58 patients received adriamycin (ADM)- and/or 5-FU-based chemotherapy. The remaining 27 patients were treated with radiotherapy alone. The median radiation dose to the nasopharyngeal region was 64 Gy, and to the initially involved cervical node, 60 Gy. The 5 year survival rates for the CDDP, the ADM/5-FU and the radiation alone groups were 61%, 47% and 42%, respectively. The cumulative incidences of local control in the CDDP, the ADM/5-FU and the radiation alone groups were 77%, 49% and 53% respectively. The CDDP group achieved the significantly better local control (CDDP vs ADM: p=0.001). The overall incidence of distant metastases was 54% in the CDDP group. On the other hand, it was 24% in the ADM/5-FU group and 22% in the radiation alone group (CDDP vs ADM: p=0.048). While the locoregional control rate was significantly better in the CDDP given group, more distant metastases were seen in this group.

Adolescent↗

Colorectal cancer recurrence in the liver: detection by PET.

Positron emission tomography (PET) has been successfully used in the imaging of various cancers. In this retrospective study, we examined clinical utility of PET in the imaging of liver metastasis from colorectal cancer. Results of PET were compared with those of ultrasonography (US) and contrast-enhanced computer tomography (CT) in 11 liver metastases seen in eight patients with recurrent colorectal cancer. The detection rates were 73% (8 of 11 metastases) by US, 73% (8 of 11 metastases) by CT, and 82% (9 of 11 metastases) by PET. PET correctly identified US-negative and CT-negative liver metastases. However, PET was negative in one patient with minute metastases. The findings in our preliminary study were in agreement with those of previous reports. A prospective study is warranted to determine the optimum role of PET in the management of patients with colorectal liver metastasis.

Aged↗