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M Haisa

Publications and source records attributed to M Haisa.

50 records · Page 3Linked to original sources

[Induction of suppressor T cells by donor-specific blood transfusion (DST): establishment of a human T cell hybridoma producing an MLR suppressing factor].

We established a human T cell hybridoma producing a mixed lymphocyte reaction (MLR) suppressing factor. Three weeks after DST, peripheral blood lymphocytes (PBL) were obtained from a recipient and were cultured for 3 days with mitomycin C (MMC)-treated donor PBL. These lymphocytes were fused with an azaguanine-resistant mutant of a human T cell leukemic cell line (CCRF-CEMAG). Four weeks after fusion, approximately 30% of the wells showed hybridoma cell growth. To select hybridoma clones with suppressive activity, irradiated hybridoma clones were added as regulator cells to the mixed lymphocyte culture. After the cloning, one clone causing suppression of the donor-specific MLR was established (termed HK40: %MLR suppression = 38.9%). Unstimulated supernatant of HK40 showed no suppressive effect on the specific MLR. In contrast, supernatant of HK40 cultured with donor PBL for 24 hrs, suppressed the donor-specific MLR dose-dependently. This primed supernatant of HK40 markedly suppressed the specific MLR when added added at the culture initiation. These findings indicate that functional clones causing suppression of the alloantigen-specific MLR can be generated in patients receiving DST, and suggest that these clones may be essential to the prolongation of kidney allograft survival.

Blood Transfusion↗

Induction of antiidiotypic antibodies by donor-specific blood transfusions. Establishment of a human-mouse hybridoma secreting the MLR-inhibiting factor.

We describe a patient transfused with 200 ml of donor fresh whole blood three times at 2-week intervals. Three weeks after the last transfusion, transplantation and splenectomy were done at the same time. Splenic cells from this DST pretreated patient were fused with murine myeloma cells (X63-Ag8, 653). With DST pretreatment, various clones were developed in vivo, and finally 69 human immunoglobulin-secreting clones were obtained. Modulation of the alloantigen-specific MLR by supernatants from 69 clones showed various degrees of suppression or augmentation. The hybridoma clone 7 and clone 2, which had been secreting IgG antibody for more than 6 months, showed some degree of suppression in the alloantigen-specific MLR (mean suppression = 63%, 46% respectively). According to the result of MLR, clone 7 antibody was directed against recipient lymphocytes and clone 2 antibody was against donor lymphocytes. Immunoprecipitation was carried out by clone 7-IgG and clone 2-IgG. Clone 7-IgG specifically precipitated 1 molecule from the recipient lymphocyte with a molecular weight of 120 KD, similar to the molecular weight range reported for T cell receptors. Clone 2-IgG precipitated a 20 KD molecule from the donor lymphocyte. The data suggest that DST induces antibodies directed against the blood donor alloantigen-specific receptors on the recipient's T lymphocytes--and, at the same time, induces antibodies against donor lymphocyte antigens. These antibodies may be essential to prolongation of kidney allograft survival following DST.

Blood Transfusion↗

[Report of a family with cancer family syndrome].

A report of multiple primary early duodenal cancer and ileocecal cancer with cancer family syndrome is presented. Analysis of 65 individuals of this family showed 7 large bowel cancers, 1 lung cancer and cancer of the uterine cervix. The characteristics of this family including increased occurrence of adenocarcinoma, especially large bowel cancer, 3 multiple primary malignant neoplasms, early age of onset of cancer and suspicion of autosomal dominant inheritance, satisfy the criteria for the cancer family syndrome. We recommend screening the individuals in this family for early signs of cancer.

Adenocarcinoma↗

[Clinical evaluation of cefmetazole for the prevention of postoperative wound infections].

The authors treated 415 patients, with injection of 4 g cefmetazole (CMZ) per day after operation of the digestive tract. In these cases, the prevention of postoperative wound infections was investigated and the following results were obtained. Out of 415 cases, 11 cases (2.7%) had postoperative wound infections; 6 cases of which were superficial wound infections and 5 cases deep wound infections. In relation to the degree of infection of the surgical field of them, 10 cases were performed with the contamination by bowel organisms and 1 case was in infected surgical field. Bacteriological examination was carried out. Twenty-four strains of bacteria were isolated and identified. The major bacterial strains identified were 6 strains of S. faecalis, 4 strains of E. cloacae and 4 strains of P. aeruginosa. These organisms were rarely sensitive to CMZ. The results suggest that the organisms causing postoperative wound infections are changing compared with the organisms of previous reports and that the use of CMZ as a postoperative medication is useful in the prevention of wound infections.

Abdomen↗

Differential expression of platelet-derived growth factor receptors in porcine fibroblasts cultured from skin and granulation tissue.

This study investigated the biological response of fibroblasts cultured from uninjured skin and granulation tissue from different stages of healing wounds to the three isoforms of platelet-derived growth factor. Fibroblasts were derived by explant culture from the skin or the granulation tissue that formed within open mesh nylon Schilling-Hunt chambers (postoperative days 10, 20, 30, and 50) which had been implanted subcutaneously in the backs of domestic pigs. Cells were cultured under identical conditions in Dulbecco's modified Eagle's medium containing 10% fetal calf serum. Mitogenic activity was measured with (3)H-thymidine incorporation into DNA. Fibroblasts from normal skin responded equally well to all of the platelet-derived growth factor isoforms in the mitogenic assays. All of the wound fibroblasts exhibited a decreased response to platelet-derived growth factor compared with those from skin. Granulation tissue fibroblasts responded to platelet-derived growth factor BB, less to platelet-derived growth factor AB, and poorly to platelet-derived growth factor AA. These results correlated with a significantly decreased growth rate of fibroblasts in culture from both 30- and 50-day postsurgical wound tissue compared with normal skin. Western blot studies of cell membrane extracts showed that wound fibroblasts contained less than 20% as many platelet-derived growth factor-alpha receptors as found in fibroblasts cultured from normal skin. No significant difference in the amount of platelet-derived growth factor-beta receptor was detected. The decreases in platelet-derived growth factor-alpha receptors are sufficient to account for the diminished response of the wound fibroblasts to all platelet-derived growth factor isoforms and the differential loss of responsiveness to platelet-derived growth factor AA. These results show that fibroblasts derived from granulation tissue of pig skin wounds exhibit a decreased growth response to platelet-derived growth factor and a decreased growth rate in culture media as compared with fibroblasts derived from uninjured skin. How these differences may relate to the physiologic characteristics of normal and healing-impaired wounds is considered.

Journal Article↗

Apoptosis in normal tissues induced by anti-cancer drugs.

To investigate the damage mediated by anti-cancer drugs in normal cells, we examined the effect of such drugs on apoptosis of normal cells of the small intestinal epithelium and the bone marrow by in situ DNA end-labelling and transmission electron microscopy. Mice received a single dose of 5-fluorouracil (5-FU) or cisplatin, or repeated daily doses of 5-FU for 7 days. In mice treated with a single dose of 5-FU 50 mg/kg or cisplatin 5 mg/kg, the number of apoptotic cells appearing in the small intestine 12 h after injection was relatively small, but increased steadily reaching a peak after 36 h and then decreasing to close to that in the control group by 48 h. In bone marrow cells, results were similar in mice treated with single doses of 5-FU 50 mg/kg but apoptosis increased much less in those treated with cisplatin 5 mg/kg. The proportion of apoptotic cells reached peak values earlier at higher concentrations of 5-FU or cisplatin both in small intestine and in bone marrow. In the mice treated repeatedly with 5-FU 50 mg/kg, the proportion of apoptotic small intestinal epithelial cells reached a succession of peaks at 48-h intervals. Mice treated repeatedly with 5-FU 50 mg/kg also showed a rapid increase in diarrhoea symptoms and a steady decrease in the height of villi. Our results suggest it may be possible to prevent the side-effects of anti-cancer drugs by inhibiting apoptosis in the gastrointestinal tract.

Animals↗