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Biomedical subjects

J Matsuoka

Publications and source records attributed to J Matsuoka.

At least 19 recordsLinked to original sources

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

Changes in growth factor levels in human wound fluid.

BACKGROUND: It has been suggested that platelet-derived growth factor (PDGF) plays a central role in wound healing. Analysis of human wound fluid revealed the presence of PDGF AA (30 kd) and monocyte/macrophage-derived growth factor (MDGF) (12 to 14 kd) in the immediate postoperative period. METHODS: The amount of PDGF AA present was assayed by Western blot analysis. The chemotactic and mitogenic potential of purified wound fluid containing PDGF AA and MDGF was determined on a responsive cell line. The biologic activity of MDGF was assayed with a cell line that is unresponsive to the PDGF AA found in wound fluid. RESULTS: Both the concentration and the biologic activity were highest in the immediate postoperative period and declined to negligible levels by 24 hours after surgery. The chemotactic activity of MDGF was highest in the immediate postoperative period and declined during the first 24 hours in a manner similar to that of the combined PDGF AA and MDGF activity. CONCLUSIONS: These data demonstrate the changing levels of PDGF and MDGF in human wound fluid over time, supporting the cascade model of wound repair. By demonstrating that MDGF acts on cell lines unresponsive to the PDGF AA found in wound fluid, these data suggest that MDGF may also play an important role in wound healing.

3T3 Cells

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

Detection of burst-promoting activity in spleens of myeloproliferative sarcoma virus-infected mice using serum-free cultures.

Myeloproliferative syndrome was induced in adult DBA/2 mice by inoculation with myeloproliferative sarcoma virus (MPSV) and Friend murine leukemia virus (F-MuLV) as a helper virus. On day 26 after infection, the spleen weighed a maximum of 2.0 g (about 30 times the control weight). Assay of multipotent stem cells in vitro showed that the more enlarged spleens contained an increased number and concentration of mixed colony-forming units (CFU-mix) (at maximum, 11 times higher than the control). When the supernatant of cultured spleen cells was added to a serum-free bone marrow cell culture with or without erythropoietin (Epo) for detection of burst-promoting activity (BPA), it enhanced erythroid mixed colony (E-mix) formation only in the presence of Epo (p less than 0.05). Even when addition of Epo was delayed, it still induced a significant number of E-mix (p less than 0.05). These findings rule out a mimic effect of Epo resembling BPA and indicate the presence of BPA in the spleen. The culture supernatant also supported the proliferation of interleukin 3 (IL-3)-dependent 32Dcl cells. Therefore, although purification of the BPA substance has not yet been accomplished, BPA in the supernatant seems to depend on the presence of IL-3, which is known to be one of the factors stimulating multipotent hemopoietic stem cells. The presence of BPA- or CFU-mix-stimulating activity in the spleen after infection might be responsible for the development of panmyelosis, which is a characteristic of MPSV-induced myeloproliferative syndrome.

Animals

Application of an interleukin 2 slow delivery system to the immunotherapy of established murine colon 26 adenocarcinoma liver metastases.

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 minipellet, using a murine hepatic metastasis model. The IL-2 minipellet consists of atelocollagen derived from natural bovine skin together with 1 x 10(6) units of recombinant IL-2. Administration of the IL-2 minipellet was performed into the spleens of BALB/c mice after translocation of the spleens to the s.c. position. Administration produced detectable serum IL-2 levels for 72 h. The IL-2 minipellet was evaluated for its efficacy against hepatic metastases from colon 26 adenocarcinoma in the BALB/c mice. Both the administration of the IL-2 minipellet alone and its combination with the injection of 5 x 10(7) lymphokine-activated killer cells resulted in significant reductions of the number of metastatic nodules. Moreover, increased survival of mice bearing colon 26 adenocarcinoma was noted in these two treatment groups. To investigate the mechanism of the IL-2 minipellet activity, we tested the lytic potential of splenocytes obtained after administration of the IL-2 minipellet in a 51Cr release assay. Cytotoxicity against YAC-1 cells and colon 26 cells was significantly augmented on Day 2 after minipellet administration. These results demonstrated that local administration of the IL-2 minipellet into the hepatic circulation was extremely effective against metastatic liver cancer.

Adenocarcinoma

The effect of anti-interleukin 2 monoclonal antibody treatment on the survival of rat cardiac allograft.

The effect of anti-interleukin 2 monoclonal antibody (anti-IL2 MoAb) and the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb were examined in heterotopic rat cardiac allografts. Mouse anti-human recombinant IL2 MoAb was obtained by the hybridoma technique. The anti-IL2 MoAb, termed 8H-10, was an IgG2a which inhibited IL2-driven [3H]TdR incorporation in cytolytic T lymphocyte line cells at a dilution of 2(6). 8H-10 was injected iv at a dose of 200 micrograms/day for 8 consecutive days, beginning on the day of transplantation. Hearts from F344 rats (RT11v1) were transplanted into ACI recipient rats (RT1av1). The mean survival time was 7.6 +/- 0.8 days in untreated controls, 9.0 +/- 1.2 days in additional controls treated with mouse anti-sheep red blood cell monoclonal antibody, and 25.3 +/- 18.4 days in the anti-IL2 MoAb (8H-10)-treated group (P less than 0.05). Furthermore, the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb (8H-10) was specifically seen in the grafted heart. In conclusion, these results suggest that IL2 may play an important role in allograft rejection and that anti-IL2 MoAb may serve as a useful immunosuppressive agent in clinical transplantation.

Animals

Two peptides related to platelet-derived growth factor are present in human wound fluid.

Platelet-derived growth factor (PDGF) has been suggested to play an important role in wound healing. In this study wound fluid collected from patients after radical mastectomy was analyzed for PDGF-related factors. Analysis revealed the presence of two PDGF-related peptides of 16-17 kDa and 34-36 kDa. These PDGF-related peptides were purified by using anti-PDGF immunoaffinity techniques and found to possess both chemotactic and mitogenic activities for NIH 3T3 cells in vitro. Surprisingly, we could not detect authentic native PDGF (30 kDa) or PDGF A or B chain in any of the wound-fluid samples examined. These results indicate that PDGF-related peptides are present in normal human wound fluid, whereas PDGF A- and B-chain peptides are absent or only present in trace amounts relative to the total PDGF-related biological activity.

Animals

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

Artificial liver support for postoperative hepatic failure with anion exchange resin (BR-601).

An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast, percent reductions in total and direct bilirubin, and in bile acids by plasma exchange were 30.9 +/- 13.3, 34.5 +/- 12.5 and 24.2 +/- 8.5%, respectively. The coma grade was improved in 4 out of 5 cases, but unfortunately the patients did not recover. In conclusion, plasma perfusion through BR-601 resin is expected to play a promising role in artificial liver support systems because of its capacity to absorb bilirubin and bile acids.

Adult