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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 1,009 records · Page 56Linked to original sources

Immune disturbance and pathogenesis of non-obese diabetes-prone (NOD) mice.

Manipulation and possible mechanism of pathogenesis in NOD mice were studied from the immunological standpoint. Disturbance of lymphocyte activity, particularly that of T-lymphocyte activity, greatly influenced the development of overt diabetes. Throughout the test period when the mice were between 24 and 30 weeks old, spontaneous diabetes in female mice was markedly suppressed by treatment with anti-thymocyte serum or with an anti-Thy 1,2 monoclonal antibody. Also, the appearance of diabetes was promoted by cyclophosphamide treatment in animals of both sexes. Evidence for the role of T-lymphocytes was provided by the experiments using the T-lymphocyte-depleted mice. Neither insulitis nor overt diabetes was observed in the athymic nude congenic mice with the genetic background of NOD even if they were given cyclophosphamide. Insulitis was induced in the athymic nude recipients by the transfer of thymocytes or of splenocytes from euthymic littermates, although an overt diabetes was not produced by cell transfer alone. An overt diabetes was induced in the congenitally athymic nude mice by a single transfer of T-lymphocytes and subsequent treatment with cyclophosphamide. From these results it can be concluded that T-lymphocytes play an obligatory role in the pathogenesis of diabetes in NOD mice.

Animals↗

Computerized glucose clamp method for the determination of insulin sensitivity in diabetic subjects.

A new, simplified computerized glucose clamp method was performed for estimation of glucose utilization at the insulin level of postprandial level. The program for the method is based on the mathematical algorithm using values of blood glucose, changes of its concentration and the desired glucose level. The coefficients of variation of the clamped blood glucose values during the last 60 minutes was 6.3 +/- 1.7(%) in normal, 3.7 +/- 0.3(%) in NIDDM, which was within satisfactory limit, and also indicated an attainment of steady state. Glucose infusion curves showed some bumps for the initial 60 min, which did not seriously affect the glucose utilization rate at steady state. In some cases, whose insulin sensitivity was high, CV was not low enough and occasional manual adjustment of K values was required. Average glucose infusion rate was 7.59 +/- 0.85 (mg/kg/min) in normal, and this was significantly lowered in NIDDM (42.3 +/- 3.4) at steady state, indicating a decreased insulin sensitivity for glucose utilization in NIDDM.

Adult↗

[The role of autologous bone marrow transplantation in cancer treatment].

Autologous bone marrow transplantation (ABMT) has been increasingly used in the treatment of malignant diseases. Since myelosuppression is one of the major dose limiting factors in cancer chemotherapy, ABMT is effective for hematologic reconstitution after marrow-lethal intensive therapy, which increases the anti-tumor effect. Diseases for which ABMT is indicated are selected on the basis of sensitivity to escalation of drug and radiation dose. These diseases include non-Hodgkin's lymphoma, leukemia, small cell carcinoma of the lung, melanoma, neuroblastoma, metastatic breast cancer and Ewing's sarcoma. Phase I and phase II studies have demonstrated that dose escalation to several times the conventional dosage may be feasible with the use of ABMT. Clinical trials of intensive therapy plus ABMT have produced encouraging results in terms of response rate and long-term survival for selected patients with poor-prognosis malignant diseases which are resistant or refractory to conventional forms of cancer therapy. When these preliminary results are analysed, it is apparent that the outcome of this treatment modality is affected by several factors such as disease status or tumor burden at the time of ABMT, the anti-tumor effect of the pretransplant intensive therapy and the extent of bone marrow invasion by tumor cells. Since ABMT is not yet well established in comparison with allogeneic bone marrow transplantation, carefully designed clinical trials will be required in order to assess the efficacy of ABMT.

Antineoplastic Agents↗

Alteration in dipeptidyl peptidase activities in cultured human carcinoma cells.

For the investigation of the possibility of its being a marker enzyme for tumor cells, the activity of dipeptidyl peptidase (DPP) IV (EC 3.4.14.5), a membrane-bound enzyme, in cultured human carcinoma cells was examined. The homogenates of three carcinoma cell lines (HeLa, KB, and K-44) contained lower glycylprolyl methylcoumarinamide (Gly-Pro-MCA) hydrolase activities at pH 8.7 (assumed to be DPP IV) and higher activities of alkaline phosphatase and gamma-glutamyl transpeptidase, which are also membrane-bound enzymes, than those of normal human fibroblasts (HF). Examination of carcinoma cells for the subcellular localization and pH optimum of Gly-Pro-MCA hydrolase activity revealed that the activity of a lysosomal enzyme that hydrolyzes Gly-Pro-MCA at pH 6.4 was markedly increased in carcinoma cells, but not in normal cells. The separation and characterization of Gly-Pro-MCA hydrolases by gel filtration, affinity chromatography, and substrate specificity demonstrated that HF have three peaks indicating DPP IV, DPP II, and an unknown enzyme, whereas the three carcinoma cell lines gave a prominent peak indicating DPP II and a trace of DPP IV. The DPP II activity was 6- to 24-fold higher in carcinoma cell lines than in HF, and it also was 2.85- to 4.13-fold higher than the DPP IV activity in carcinoma cell lines but was 10-fold lower in HF. These clear enzymatic differences between carcinoma cells and normal HF may be useful as a marker of malignancy.

Alkaline Phosphatase↗

[Serial changes in cardiovascular dimensions and left ventricular function after surgery of valvular heart disease: a follow-up study by echocardiography].

Serial changes in cardiac function after surgery were studied in 84 patients with various valvular heart diseases using M-mode and two-dimensional echocardiography (2-DE). The results were as follows: 1. Serial postoperative changes in cardiac dimensions and left ventricular functions were well documented by M-mode and 2-DE. 2. The change in left ventricular function became most pronounced one month after surgery, and remained unchanged in many patients during the subsequent observation periods. 3. Open mitral commissurotomy (OMC) and mitral valve replacement (MVR) were compared as to their benefits for patients with isolated mitral stenosis (MS) accompanied by left ventricular dysfunction, and MVR proved superior to OMC in terms of magnitude of functional improvement. 4. (a) Ejection fraction (EF) in patients with left ventricular volume overload was overestimated due to the influence of increased preload. Accordingly, EF which tended to be depressed one month after surgery was judged to reflect altered loading conditions; it did not represent myocardial damage caused by valve replacement. (b) In patients who had MVR or aortic valve replacement (AVR) without postoperative heart failure, EF remained unchanged in the MVR group after a lapse of one month postoperatively, while it tended to improve in the AVR group. This difference was thought to be caused by changes in left ventricular systolic overload resulting from correction of regurgitation. (c) In patients with MR and postoperative heart failure, there was a tendency for EF to decrease after a lapse of one month postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of physical exercise training on cardiac function and graft patency after coronary artery bypass grafting.

The effects of physical exercise training after coronary artery bypass grafting on recovery of cardiac function and graft patency were studied in 115 patients. The patients were divided into Group I (N = 60) with and Group II (N = 55) without a scheduled rehabilitation program. The rate of graft patency was 98% in Group I and 80% in Group II. After operation, the exercise cardiac index and stroke index were significantly higher in Group I than in Group II. The exercise stroke index increased significantly in Group I, but not in Group II. The variables affecting graft patency, examined by a stepwise method, included double product, cardiac index, stroke index, and left ventricular end-diastolic pressure during postoperative exercise conditions, and postoperative exercise training. The multiple coefficient for these five variables was 0.459 (p less than 0.01). Our findings suggest that physical exercise training should be started as early as possible after coronary artery bypass grafting to improve graft patency and recovery of cardiac function.

Cardiac Output↗