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K Sakagami

Publications and source records attributed to K Sakagami.

At least 73 records · Page 4Linked to original sources
PubMed1992

Ex vivo perfusion of canine pancreaticoduodenal allografts using class-II-specific monoclonal antibody delays the onset of acute rejection.

In the following study, we investigated whether ex vivo perfusion of canine pancreaticoduodenal allografts prior to transplantation using a class-II-specific monoclonal antibody (MoAb) OKIa1) could prevent acute rejection. Untreated grafts were rejected within 6 days after transplantation, and all of these recipients suffered severe hyperglycemia. In contrast, in recipients who received grafts which underwent ex vivo class-II-specific MoAb perfusion treatment, the mean urinary amylase levels were sustained significantly higher (11,733 +/- 4493 vs. 3274 +/- 2108 U/L on day 7, P < 0.005), and mean fasting blood glucose (FBG) levels remained within the normal range (13.4 +/- 5.8 vs. 23.4 +/- 3.9 mM on day 7, P < 0.0005). Low doses of cyclosporin A (CsA) were necessary in order to maintain lower FBG levels. Histopathology analysis on day 7 after transplantation showed that endotheliitis and necrosis were much less prominent in the MoAb-treated grafts. In the light of our results, we conclude that ex vivo perfusion of canine pancreaticoduodenal allografts using a class-II-specific MoAb is effective in delaying the onset of acute rejection, and low doses of CsA could extend this effect.

Animals↗
PubMed1992

Analysis of suppressor T cells induced by donor-specific transfusion (DST): establishment of a human T cell hybridoma producing an antigen-nonspecific suppressor factor.

Formation of suppressor T cells (Ts) induced by donor-specific transfusion (DST) is one of the most commonly suggested mechanisms for the beneficial effect of DST. In this study, we established a human T cell hybridoma derived from the peripheral blood lymphocytes (PBL) of a DST-treated patient, which produced an antigen-nonspecific suppressor factor. Post-DST PBL were fused with an azaguanine-resistant mutant of a human T cell leukemia cell line, CCRF-CEM(AG). After selection and cloning, we established one clone producing the mixed lymphocyte reaction (MLR) inhibitory factor (C524: 18%-43% suppression). Suppressive activity of the supernatant obtained from C524 after activation by PHA was highly augmented (64%-88% MLR suppression). This factor inhibited MLR dose-dependently in an antigen-nonspecific and HLA non-restricted manner. These results indicated that Ts clones could be generated in patients receiving DST and that the immunoregulatory factors produced by activated clones may play a role in the prolongation of renal allograft survival.

Antibody Specificity↗
PubMed1992

Effects of interleukin 2 receptor b chain (P75)-specific monoclonal antibody on the generation of cytotoxic T lymphocytes and suppressor T cells in mixed lymphocyte culture.

The interaction of interleukin 2 (IL-2) with its receptor (IL-2R) plays an essential role in the proliferation and differentiation of T cells. The IL-2R beta-chain is considered to function directly in the intracellular signal transduction. In this study, we investigated using a newly established IL-2R beta-chain-specific monoclonal antibody (MAb) (TU-25) and an IL-2R alpha-chain-specific MAb (H-31). The IL-2-induced proliferation of concanavalin blasts and the mixed lymphocyte reaction (MLR) were suppressed by TU-25 in combination with H-31. This combination had a greater suppressive effect than each of them alone. The generation of cytotoxic T lymphocytes (CTL) using a cell-mediated lympholysis (CML) assay, was not inhibited by TU-25 alone. TU-25 in combination with H-31 suppressed the generation of CTL completely in this assay even if recombinant IL-2 (rIL-2) was added. Although the CTL generation was inhibited, cells that suppressed a fresh MLR were preserved. Our study suggests that the combination of TU-25 with H-31 completely blocks the functional high-affinity binding site of IL-2 but does not inhibit the generation of suppressor cells. This may lead to immunosuppressive therapy using an IL-2R beta-chain-specific MAb in combination with an IL-2R alpha-chain-specific MAb in clinical organ transplantation.

Antibodies, Monoclonal↗
PubMed1992

Renal transplantation from HLA-haploidentical living-related donors: the effects of donor-specific blood transfusions and different immunosuppressive regimens.

One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.

Blood Transfusion↗
PubMed1992

Assessment of lymph node metastasis and vessel invasion in early rectal cancer.

Thirteen patients with rectal carcinoma seen between December 1980 and December 1990 have been reviewed to determine the risk of lymph node metastasis and its implication for subsequent treatment. The mean age was 64 years (from 38 to 79; 9 males, 4 females). The site of the tumor was predominantly in the lower rectum (53.8 percent). The polypoid (I) and flat-elevated ulcerated (IIa + IIc) subtypes were detected in seven and six lesions, respectively. Sphincter-saving techniques were carried out in eight cases, and five cases required Miles' operation. Neither postoperative complications nor deaths were noted. The mean follow-up period was 57 months (6 to 133 months). No recurrence or distant metastasis was found during this follow-up. IIa + IIc subtype lesions with deep submucosal invasion at or beyond Smlc level were closely related with lymphatic and vascular invasion. Although this association was not necessarily accompanied by an increased number of involved lymph nodes, major surgical resection is suggested in such IIa + IIc cases due to an increased possibility for lymph node metastasis.

Adult↗
PubMed1992

The impact of triple drug immunosuppression on clinical results of cadaveric kidney transplantation: a comparison of conventional immunosuppression.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.

Adult↗
PubMed1992

Laparoscopic cholecystectomy report of 30 cases.

Laparoscopic cholecystectomy (LSC) was attempted in 30 patients and was accomplished in 29 during the nine months between March and November 1991. Twenty eight patients had cholelithiasis with or without adenomyosis, and two had adenomyosis of the gall-bladder. Mean operative time was 219 min and postoperative pain was slight. Two complications (6.9%), including necrosis of the common hepatic duct and subcutaneous emphysema, were encountered. Patients with subacute and severe chronic cholecystitis were included in the cases. Thus this technique is recommended for almost all patients who require the removal of the gall-bladder for benign diseases.

Adolescent↗
PubMed1992

Can cytokines prolong survival in ampullary neuroendocrine carcinomas?

Herein we report the case of an ampullary tumor in a 53-yr-old Japanese woman who presented in March 1988 with abdominal pain, weight loss, and jaundice. A pancreatoduodenectomy was carried out, and 3 months later, she presented with a Virchow's node. She was initially treated with cytokines plus 5-fluorouracil derivative, resulting in a complete remission lasting over a year. However, in July 1990, the Virchow's node reappeared and was surgically excised. Histology revealed a small-cell neuroendocrine carcinoma (SCNC) similar to the prior ampullary tumor, which was confirmed by immunohistochemical studies and electron microscopic examination. The patient was discharged within 1 month, remaining disease-free over a 18-month period following excision. We suggest that the use of cytokines can be effective, and can increase survival in gastrointestinal neuroendocrine tumors.

Ampulla of Vater↗
PubMed1991

Augmentation of antitumor effect on syngeneic murine solid tumors by an interleukin 2 slow delivery system, the IL-2 mini-pellet.

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 mini-pellet, in two murine solid tumor models, and also investigated the enhancement of its therapeutic effect by serial administration. The IL-2 mini-pellet contains 1 x 10(6) units of IL-2 and releases it slowly in vivo. In our experiment, the IL-2 mini-pellet was administered subcutaneously near the tumor site in combination with the intravenous injection of lymphokine-activated killer (LAK) cells. When this regimen was given on days 8 and 11 after the subcutaneous inoculation of Meth A fibrosarcoma into BALB/c mice, tumor growth was significantly inhibited (p less than 0.05) compared to tumor growth in untreated controls. Moreover, the IL-2 mini-pellet alone was also effective in inhibiting tumor growth. In another experiment, MH134 hepatoma was inoculated into C3H/He mice. Both administration of the IL-2 mini-pellet alone and in combination with LAK cells resulted in complete tumor regression in four of five mice. In a third experiment, serial administration of the IL-2 mini-pellet at 3- or 5-day intervals prolonged the suppression of Meth A fibrosarcoma growth in BALB/c mice. These results suggested that the IL-2 mini-pellet could be applied to cancer immunotherapy and that its antitumor effect could be prolonged by serial administration.

Animals↗