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Biomedical subjects

K Sakagami

Publications and source records attributed to K Sakagami.

At least 127 records · Page 7Linked to original sources

Effects of anti-interleukin-2 receptor antibody and cyclosporin A on human T cell proliferation in primary mixed lymphocyte reaction.

Effects of anti-IL2 receptor antibody (anti-IL2 RAb) and cyclosporin A (CsA) on human T cell proliferation in primary mixed lymphocyte reaction (MLR) were investigated. Both agents inhibited the proliferative response induced by alloantigen in a dose dependent manner when they were added at the initiation of culture. We also analyzed the expression of activation antigen on responder cells and the kinetics of T lymphocyte subset proliferation during MLR using two-color flow cytometry. Cells expressing activation antigens, such as IL-2 receptor and HLA-DR, were found less frequently in anti-IL2 RAb-treated MLR culture (4.8%) than in CsA-treated MLR culture (16.5%) on day 6. Furthermore, proliferation of CD8+CD11- cells, considered a cytotoxic T cell subset, were inhibited significantly more in anti-IL2 RAb-treated MLR culture than in CsA-treated MLR culture. We further demonstrate that CsA inhibits preferentially IL-2 production and anti-IL2 RAb inhibits T cell proliferation by blocking an absorption of IL-2 by activated lymphocytes. These data suggest that anti-IL2 RAb selectively inhibits alloantigen-activated T cells and may prove to be of significant value as an immunosuppressive agent in clinical organ transplantation.

Antibodies↗

Clinical application of cascade filtration combined with glassbead adsorbents in cancer patients.

Cascade filtration (CF) was applied to patients with advanced cancers. To selectively remove immunosuppressive factors with molecular weight lower than albumin, adsorbents combined with CF were examined. Among 11 kinds of adsorbents, glassbead adsorbents with pore size 100A were the most effective in adsorbing such substances. Clinically, a column packed with glassbead adsorbents was concomitantly used with CF. The second filtrate was passed through the column and returned to the patient. The removal rate of immunosuppressive substances with molecular weight lower than albumin was only 20% by CF alone, but more than 50% by CF combined with glassbead adsorbents. Clinical symptoms such as severe back pain and general malaise were drastically improved during and after therapy. These results suggest that CF combined with glassbead adsorbents is an effective adjunctive modality to cancer therapy.

Adsorption↗

Immunological detection of 22K protein in sporulating cells of Bacillus megaterium ATCC 12872.

The synthesis and deposition of 22,000-dalton (22K) spore coat protein were examined immunochemically on the sporulating cells of Bacillus megaterium ATCC 12872 using the antibody to purified 22K spore coat protein. This antibody cross-reacted with 44K and 25K proteins in immunoblot analysis of dormant spore coat proteins. Immunoblot analysis on the sporulating cells showed that 22K protein was detected from t8 in forespore coat protein fractions. Sandwich enzyme immunoassay revealed that 22K protein in the spore coat protein fraction appeared at t6 and reached a plateau at t9, and 22K protein in the mother cell cytoplasmic fraction was detected at only t7 and t8 at a very low level.

Bacillus megaterium↗

Prolongation of cardiac allograft survival in rats by treatment with anti-interleukin 2 antiserum.

Interleukin-2 (IL2) is the obligatory signal for both T cell mitogenesis and in vitro generation of alloreactive cytotoxic T lymphocytes (CTL). An investigation was made to determine whether an antibody directed against IL2 would suppress the rejection reaction of rat cardiac allografts. Rabbit anti-interleukin 2 (anti-IL2) antiserum was obtained by immunizing at 2 week intervals over a period of 8 weeks with 10(6) U of recombinant human IL2 along with complete Freund's adjuvant. The bioassay for inhibition of IL2 activity by anti-IL2 antiserum was carried out in conjunction with the IL2-dependent cytotoxic T cell (CTLL cell) assay. Cardiac allografts of F344 rats were heterotopically transplanted into ACI rats. Seven daily doses of 1 ml of anti-IL2 antiserum were administered intravenously following transplantation. IL2-driven [3H]thymidine incorporation in CTLL cells was significantly inhibited by rabbit anti-IL2 antiserum. Graft survival in the anti-IL2 serum-treated group was significantly prolonged in a dose-dependent fashion compared to control groups. In conclusion, these results indicate that rabbit anti-IL2 antiserum may prove to be of significant value as an immunosuppressive agent in clinical organ transplantation.

Animals↗

Effects of a single donor-specific blood transfusion on the survival of rat cardiac allografts.

It is now well recognized that pre-transplant donor-specific blood transfusion (DST) has a beneficial effect on the survival of allografts. To determine the optimal interval between DST and transplantation, and to analyze the mechanisms of this effect, the survival of cardiac allografts to rats which received a single DST was examined. The cardiac allograft survival was found to be prolonged when the DST was performed 1 to 6 weeks before grafting. In addition, recipient rat sera collected 1 to 6 weeks after a single DST showed significant inhibition of a mixed lymphocyte reaction (MLR). This MLR inhibition correlated with prolongation of survival of histoincompatible rat cardiac allografts. It thus appears that a single DST given from 1 to 6 weeks before transplantation has a beneficial effect on allograft survival and that MLR inhibition may be essential for inducing the effect of transfusion on organ transplantation.

Animals↗

Radical block resection of hepatoduodenal ligament for carcinoma of the bile duct with double catheter bypass for portal circulation.

A new concept of radical block resection of the hepatoduodenal ligament for carcinoma of the bile duct and new double bypass technique of portal circulation for the procedure were introduced. Clinical experiences of six patients were reported. By combined use of radical block resection of the hepatoduodenal ligament and double bypass technique, the radical resectability of carcinoma of the bile duct became a reality, and improvement of postoperative survival rate is expected.

Biliary Tract Neoplasms↗

Effects of serum fractions obtained from cancer patients by double-filtration plasmapheresis on tumor growth and metastasis in mice.

We administered serum fractions obtained from cancer patients by double-filtration plasmapheresis (DFPP) to cancer-bearing mice to examine the effects on tumor growth and metastasis. Fraction 1 (whole plasma), fraction 2 (a plasma fraction containing substances with higher particle size), fraction 3 (a plasma fraction containing substances with smaller particle size) and saline were administered intravenously to cancer-bearing mice for 10 days following the inoculation of tumor cells. The tumor growth and metastasis in mice administered fraction 2 was far more rapid than that in the control mice. On the other hand, tumor growth in mice administered fraction 3 was significantly delayed compared with that in mice injected with fraction 2. These results suggest that factors in the higher particle-size fraction of cancer patients' sera promote the growth and the metastasis of tumors in mice, and that DFPP, which remove these factors, is an effective therapy against cancer.

Animals↗