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Biomedical subjects

S Fuchimoto

Publications and source records attributed to S Fuchimoto.

At least 73 records · Page 4Linked to original sources

A subrenal capsule assay for testing the effect of anticancer drugs against human tumors.

Fresh surgical explants of solid tumors obtained from 50 patients were tested against six chemotherapeutic agents in the in vivo subrenal capsule assay. Control growth adequate to meet evaluable assay criteria was obtained in 36 of 50 tumors (72.0%). With activity criteria set at current drug screening levels as a change in modifidd PAPAN score in less than or equal to -2.0 for the SRC assay, 36.1% of the human tumors evaluable and 11.6% of drugs tested were sensitive, respectively. Our research reveals that gastric cancers respond to drugs about 2.5-fold higher than colorectal cancers. Comparisons were made of the drug sensitivity in terms of histologic differentiation, and it was strongly suggested that the sensitivity of the poorly differentiated type was higher than that of well or moderately differentiated type.

Adenocarcinoma↗

Natural killer activity of peripheral blood lymphocytes and its relation to histopathological factors of lung cancer.

This investigation was intended to determine whether the natural killer (NK) activity of peripheral blood lymphocytes (PBL) correlated with the histopathological factor, which is thought to be a result of a balance between tumor aggression and host resistance. The NK activity of PBL from 60 patients with lung cancer was measured by the lysis of 51Cr-labelled K562 target cells. The activity was significantly decreased with advancing stages of the disease, and inversely correlated with increased immunosuppressive substance levels of the serum. Histopathological factors, such as low grade pleural invasion of the tumor and abundant lymphoid cell infiltration around the tumor, were significantly associated with the high NK activity of PBL. These results show that a decrease in NK activity may play a role in identifying those individuals with a greater risk of cancer development.

Cytotoxicity Tests, Immunologic↗

In vitro synergistic effects of natural human tumor necrosis factor and natural human interferon-alpha.

Tumor necrosis factor and interferons are multifunctional cytokines. The present studies were undertaken to investigate the biologic interactions of highly purified natural human tumor necrosis factor and highly purified natural human interferon-alpha, which were derived from a B cell acute lymphatic leukemia line (BALL-1 cells) sensitized with hemagglutinating virus of Japan (HVJ). Combined treatment with natural human tumor necrosis factor and natural human interferon-alpha synergistically inhibited the in vitro proliferation of P4788 cells derived from a human colon cancer. Flow cytometric analysis of the cell cycle of asynchronous cells indicated that target cells treated with natural human tumor necrosis factor alone accumulate in the S phase. This accumulation in the S phase of the cell cycle was augmented by combined treatment with natural human tumor necrosis factor and natural human interferon-alpha. The growth inhibitions appeared to be a result of arrest in the S phase of the cell cycle. Combined treatment with these cytokines had potent cytostatic and cytotoxic effects on most of the tested malignant cell lines of human epithelial origin.

Cell Cycle↗

Beneficial effect of donor-specific blood transfusions (DST) on living-related kidney allograft survival.

The survival rate of 19 patients who underwent living-related kidney transplantation after donor-specific blood transfusions (DST) was compared with that of 32 historical controls receiving transplants without DST. The graft survival rate of the DST group was 82% after two and three years. The graft survival rate of the DST group was significantly better than the 53% rate after two years obtained with the 32 historical controls (p less than 0.05). We tested sera from 16 DST-treated recipients to study the beneficial effect of DST on kidney allograft survival using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrated that MLC inhibitory factors were induced in the serum of the recipient after completion of DST. This inhibition of MLC was observed by treatment of responder lymphocytes with serum obtained three weeks after DST plus rabbit complement. The inhibitory effect was also specific for responder cells in anti-donor MLC. Regarding the correlation with rejection episodes, these MLC inhibitory factors were often observed in the non-rejection group (p less than 0.05). The data suggest that such factors may be anti-idiotypic antibodies and be associated with prolonged graft survival.

Adult↗

[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↗

Active enhancement of rat cardiac allografts induced by donor specific semisoluble antigens.

Active enhancement was induced in inbred rats with cardiac allografts using semisoluble antigens. The optimal time of antigen pretreatment and optimal dose of semisoluble antigens were examined. The presence of serum blocking factors in the sera of rats having had allografts for a long time was examined with a macrophage migration inhibition test and lymphocyte microcytotoxicity assay. Since the blocking factors of macrophage migration inhibition were increasing on the 7th day, that day was determined to be the optimal time of antigen pretreatment. The mean survival time (MST) of cardiac allografts in untreated rats was 17.2 +/- 7.5 days. Semisoluble antigens were administered at 2 mg/kg body weight 7 days before the graft, 4 mg/kg 7 days before the graft and 2 mg/kg divided over three days, 15, 8 and 1 day before the graft, and the MSTs of cardiac allografts of rats receiving these treatments were 71.2 +/- 39.9, 62.6 +/- 42.2 and 79.3 +/- 31.0 days, respectively. The MST in each group of the treated rats was significantly longer than that of the control group (p less than 0.01). Rejection of the allograft, however, was accelerated in a group treated with 8 mg/kg 7 days before the graft (MST: 8.4 +/- 3.2 days). Serum blocking factors were detected in the sera of approximately half of the rats having cardiac allografts which survived a long time.

Animals↗

[Clinical evaluation of a serum immunosuppressive (IS) substance in various diseases].

The IS substance (molecular weight: 52,000, pI: 2.7-3.3) levels in the serum was examined in patients with various diseases. The IS substance levels in patients with gastric, colorectal, biliary-pancreas and esophageal cancer were significantly higher than those in healthy volunteers. The level of IS substance increased in accordance with advance of cancer, showing the highest level in advanced and recurrent cancer patients. In benign disease patients, high levels of IS substance were also observed in the serum of infectious diseases and chronic renal failure. In contrast, patients with liver cirrhosis had a definite low level of IS substance. When the IS substance level was compared with other parameters in cancer patients, a definite correlation was found with immunosuppressive acidic protein and alpha 2 globulin. However, there was no correlation with skin reaction, lymphocyte number, T-cell number, or PHA induced lymphocyte blastgenesis. It is suggested that the IS substance level is a useful indicator to judge the extent of disease before operation and to estimate the clinical course after operation.

Carcinoembryonic Antigen↗

Early diagnosis of acute renal allograft rejection: efficacy of macrophage migration inhibition test as an immunological diagnosis.

1. Three cases of acute rejection were detected by macrophage migration inhibition tests (MIT) conducted directly on seven patients who had received renal allografts. The macrophage migration inhibitory factor (MIF) activity was positive in all cases 1-2 days before the appearance of acute rejection. 2. After the administration of a high dose of Solu-Medrol (1g/day for 3 days) to suppress the acute rejection, MIF activity recovered to its normal level 3 days later. These findings seem to indicate that MIT yields immunologically useful criteria for the early detection of an acute rejection.

Adult↗

Effects of cyclosporine A on experimental hepatic metastases of mouse colon-26 tumour.

Cyclosporine A (CSA), an immunosuppressive agent with apparently selective effects on T lymphocytes and little myelotoxicity, was tested for its effects on hepatic metastases by inoculation of mouse colon-26 tumour cells into the portal vein in male CDF1 mice. CSA, given subcutaneously in daily doses of 10-50 mg/kg/day, for 22 days, significantly increased the incidence of hepatic nodules. This increase was positively correlated with the CSA dose. When 5-fluorouracil was injected at a dose of 15 mg/kg/day every other day after the inoculation of tumour cells a highly significant reduction in the incidence of metastases was seen (compared with the controls). This strong inhibitory effect of 5-fluorouracil on metastasis was almost completely suppressed when mice were treated with CSA concomitantly. The results suggest that CSA affects the host immune system, accelerating the production of hepatic metastases.

Adenocarcinoma↗

Metachronous liver metastasis of colorectal cancer: timing of occurrence and efficacy of adjuvant portal chemotherapy.

We estimated the time of occurrence of metachronous liver metastasis in colorectal cancer patients from tumor diameter and doubling time. Micro-metastasis was present prior to operation in most patients and a few metastatic cases could have been initiated by the surgical procedure. Portal chemotherapy is more effective against liver metastasis than intravenous infusion because a higher drug concentration in the liver can be obtained. This efficacy of portal chemotherapy on survival was also observed in a rat model. Thus perioperative adjuvant treatment should be undertaken for metastasis which already existed before the operation and adjuvant chemotherapy via portal vein is the treatment of choice. The no touch isolation technique is also needed to avoid spreading of tumor cells during surgery.

Animals↗