Biomedical subjects
Publications and source records attributed to M Harada.
Specific antibody against purified alkaline phosphatase from bovine dental pulp was raised in a rabbit. Immunological analyses by Ouchterlony double-gel diffusion and quantitative immunoprecipitation showed that there was neither a detectable antigenic difference between liver and pulp alkaline phosphatases nor a detectable cross-reaction with the intestinal enzyme.
The effect of chronic administration of isoproterenol on the plasma membrane of acinar cells in the rat submandibular gland was studied by biochemical and immunohistochemical methods, using dipeptidyl peptidase (DPP) IV as a marker enzyme. Chronic isoproterenol treatment led to a marked reduction of DPP IV activity as well as of its immunoreactivity in the gland. Its effect progressively increased with the age of the animals. The present study showed that chronic treatment with isoproterenol caused a qualitative alteration of the plasma membrane of the luminal surface in acinar cells of the rat submandibular gland, and that the effect of the drug on the plasma membrane was dependent on the developmental stage of the acinar cells of the gland.
Intraduodenal administration of 70% MeOH extract of Japanese Angelica root (3 g/kg) and Peony root (3 g/kg) increased uterine contractile activities in anesthetized rabbits. The activities of both extracts shifted to the aqueous layer (positive at a dose of 1 g/kg) with successive fractionation of the extracts with hexane and BuOH, indicating contribution of a hydrophilic principle(s) to the effect. In some animal preparations, inhibiting effect of the extracts on uterine contraction was noted after the uterotonic effect terminated. The aqueous fraction (40 mg/kg) after being treated with hexane and BuOH also produced uterine contraction along with decrease of blood pressure through i.v. route, which was greatly inhibited by pretreatment of atropine, suggesting participation of cholinergic components in the effect of both extracts.
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Interstitial pneumonia, especially that due to cytomegalovirus (CMV), is a frequent and serious complication of allogeneic bone marrow transplantation (BMT). The influence of allogeneic BMT on the development of CMV pneumonia was investigated in comparison with that of autologous BMT. Data on 37 patients (23 allotransplants and 14 autotransplants) who survived for longer than one month were reviewed. All were conditioned for the transplant with marrow-lethal cytoreductive therapy. Interstitial pneumonia occurred in 15 allotransplant patients (65%) and in five autotransplant patients (36%), and was fatal in 10 allotransplant patients (67%) and in two autotransplant patients (40%), with no statistically significant difference between the two groups of patients. However, the high incidence of CMV pneumonia in allotransplant patients presented a striking contrast to that in autotransplant patients (13 of 23 versus one of 14, p less than 0.01). CMV pneumonia was closely associated with the occurrence of graft-versus-host disease (GVHD). Moreover, the data inferred that both delayed posttransplant immunologic recovery and numerous transfusions of blood products from multiple random donors predispose allotransplant patients to CMV pneumonia. Though combination therapy with acyclovir, interferon-alpha (IFN) and prednisolone seemed to be somewhat effective further studies are needed to verify its benefit considering that all the patients (five allotransplants and one autotransplant) who survived CMV pneumonia showed a significant seroconversion to CMV. On the other hand, neither IFN nor nonspecific gamma-globulin proved to be effective in preventing CMV pneumonia. It is thus suggested that special attention be focused not only on the development of better methods to prevent GVHD and improve posttransplant immunologic recovery but also on reduced exposure to exogenous CMV.
We studied the effects of alloantigen-stimulated lymphocytes in the regulation of hematopoiesis. Alloantigen-stimulated lymphocytes were harvested on days 2 to 3, days 6 to 7, or days 9 to 10 of MLC and were tested for their effects on granulocyte/macrophage progenitor cells (CFU-C). Dose-dependent suppression of CFU-C was observed when alloantigen-stimulated lymphocytes from days 6 to 7 and days 9 to 10 MLC were added to the cultures of autologous or allogeneic bone marrow cells for CFU-C assays. Suppressive activity was detected in the T cell fraction but not in the non-T cell fraction. For further characterization of these CFU-C/suppressor cells, alloantigen-stimulated lymphocytes were treated with radiation (2000 rad) or with monoclonal antibodies against T cell subsets and complement (C) before culture. Suppressive activity was completely abolished by treatment with OKT8 or OKIa1 antibodies and C whereas suppression was retained after radiation treatment. These observations suggest that CFU-C/suppressor cells can be induced by alloantigen stimulation in MLC and that they are radioresistant OKT8+ and Ia+ T cells.
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The effectiveness of therapeutic granulocyte transfusions was studied in a controlled trial involving 75 granulocytopenic patients with severe infections. Patients who had granulocyte counts of less than 200/mm3 and no response to antibiotic therapy were assigned to receive antibiotic therapy alone or granulocyte transfusions plus antibiotic therapy. Granulocytes were collected by filtration leukapheresis (FL), intermittent flow centrifuge leukapheresis (IFCL) or continuous flow centrifuge leukapheresis (CFCL). Therapeutic effects of granulocyte transfusions were evaluated on the basis of 20-day survival after entry into the study. The patients were divided into three groups: 1) 22 patients received antibiotic therapy alone for 29 infectious episodes (control group); 2) 27 patients received 131 transfusions of granulocytes collected by FL for 31 infectious episodes (FL group); 3) 26 patients received 139 transfusions of granulocytes collected by IFCL and CFCL for 27 infectious episodes (IFCL & CFCL group). The overall survival of the transfused patients was not significantly different from that of the untransfused patients. Similarly, there was no significant difference in survival between the transfused and untransfused patients when the data concerning septicemia were analyzed. When patients showed bone-marrow recovery, which was indicated by recovery of granulocytes to 500/mm3 or more during the study, 20-day survival was observed in 13 of 14 untransfused patients and in all of 26 transfused patients. In contrast, the survival rate for the patients without bone-marrow recovery was 13% (2/15) in the control group, 39% (7/18) in the FL group and 57% (8/14) in the IFCL & CFCL group respectively. Thus, the survival rate was significantly higher for the transfused than for the untransfused patients. These observations suggest that therapeutic granulocyte transfusions may be of limited value in improving the outcome of severe infections in persistently granulocytopenic patients. Since bone-marrow recovery is a critical factor for the prognosis of severe infections, therapeutic granulocyte transfusions do not provide any beneficial effects in granulocytopenic patients whose bone-marrow function will recover.
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Fifteen patients with advanced or resistant non-Hodgkin's lymphoma or solid tumors were treated with marrow-lethal intensive therapy followed by autologous bone marrow transplantation. Seven of the patients are still alive 7.5-48.5 mo after transplantation; four of them are surviving in complete remission more than 3 yr after transplantation. Treatment failures were due to relapse, in four patients, resistance to the treatment in two and fatal complications in five. The fatal complications were non-marrow toxicity due to overdoses in two patients. and interstitial pneumonia in three. Relapse is one of the major problems to be solved in autologous marrow transplantation. When our data were analyzed in relation to relapse after transplantation, the factors responsible for relapse were found to include 1) tumor burden before transplantation, 2) therapeutic effectiveness of the conditioning regimen, and 3) contamination of cryopreserved marrow with tumor cells. Our data indicate that the combination of intensive therapy and autologous marrow transplantation will be the treatment of choice with acceptable risks for selected patients with advanced or resistant malignant disease with a poor prognosis and that it can produce remission in a substantial proportion of these patients.
By means of a national survey, records of 69 patients who underwent allogeneic bone marrow transplantation (BMT) from September 1975 through June 1983 were collected from 11 participating hospitals of the Total Body Irradiation (TBI) Subcommittee in Japan. The patients were divided into 34 with acute lymphocytic leukemia (ALL), and 35 with acute nonlymphocytic leukemia (ANLL). One-year survival rates were 47% and 25% in ALL and ANLL patients, respectively. Uninfected patients in remission at the time of BMT had significantly higher survival rates than the remaining patients. Significantly favorable prognostic factors were remission at the time of BMT, absence of infection at the time of BMT, younger age, preparation with low-dose-rate fractionated TBI and cyclophosphamide, and mild graft-versus-host disease (GVHD) for patients with acute leukemia treated with allogeneic BMT based on the external criterion variable of 180-day survival. By using Hayashi's quantification II, the ratios of correct discriminations for 180-day survival were calculated as 91% (31/34) and 86% (30/35) for ALL and ANLL, respectively.
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