Search PubMed⌕ Search

Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 1,045 records · Page 58Linked to original sources

Absence of insulitis and overt diabetes in athymic nude mice with NOD genetic background.

NOD mice spontaneously develop diabetic syndrome similar to that of insulin-dependent diabetes mellitus in man. Insulitis, i.e., lymphocytic infiltration into the pancreatic islets is the etiologic pathological lesion in the development of diabetes mellitus in NOD mice. In the present study, we examined the role of the T cell in the development of insulitis and overt diabetes in NOD mice using NOD athymic and euthymic congenic mice. None of the NOD athymic mice developed insulitis at 9 weeks of age or overt diabetes up to 30 weeks of age. In contrast, NOD euthymic littermates showed almost the same incidences of insulitis and overt diabetes as those of NOD mice. These observations suggest that T cells are essential for the development of insulitis and overt diabetes in NOD mice.

Animals↗

Suppression of overt diabetes in NOD mice by anti-thymocyte serum or anti-Thy 1, 2 antibody.

Effects of anti-thymocyte serum (ATS) and anti-Thy 1, 2 monoclonal antibody on the spontaneously occurring diabetes in NOD mice were examined. Spontaneous diabetes in female mice was markedly suppressed by intravenous injection of rabbit anti-mouse thymocyte serum diluted to 1:4 on three consecutive days during the time period from 70 to 100 days after birth; the cumulative incidence of overt diabetes upto 195 days of age was greatly reduced and the onset of diabetes was delayed. Similar effect was observed with anti-Thy 1, 2 antibody treatment. These findings suggest that T lymphocytes play a role in the production of spontaneous diabetes in this mouse strain.

Animals↗

New alpha 2-adrenergic blocker (DG-5128) improves insulin secretion and in vivo glucose disposal in NIDDM patients.

Effects of oral administration of DG-5128, a new oral hypoglycemic agent, on glycemic control after a mixed meal and an in vivo glucose disposal were measured in subjects with nonobese non-insulin-dependent diabetes mellitus (NIDDM). Oral administration of DG-5128 significantly (P less than .05) enhanced insulin secretion both 30 and 60 min after a mixed meal (550 kcal), with a concomitant decrease in postprandial plasma glucose levels at 60 and 120 min. Glucose disposal rate between the 2nd and 4th h of a euglycemic insulin clamp, developed through a constant infusion of insulin (0.77 mU X kg-1 X min-1) together with somatostatin (80 ng X kg-1 X min-1), was 2.5-fold higher in a DG-5128-treated group (P less than .01) than in a control group. However, there was no difference between the two groups in either plasma glucose concentration or plasma insulin concentration at either the 2nd or the 4th h. These results indicate that DG-5128 is effective in controlling plasma glucose levels in subjects with NIDDM by stimulation of both insulin secretion and in vivo glucose disposal.

Adrenergic alpha-Antagonists↗

Effect of activated lymphocytes on the regulation of hematopoiesis: enhancement and suppression of in vitro BFU-E growth by T cells stimulated by autologous non-T cells.

Autologous mixed lymphocyte culture (AMLR) is an immunologic response with memory and specificity and plays a role in immune regulation. Effects of T cells activated by AMLR were studied in the regulation of in vitro erythropoiesis. AMLR-activated T cells were cocultured with autologous non-T, nonphagocytic peripheral blood mononuclear cells for assaying erythroid progenitor cells (BFU-E). T cells activated for 3 days in AMLR showed significant enhancement of in vitro colony growth by BFU-E. In contrast, activated T cells from day 7 AMLR caused significant suppression of BFU-E growth. Both enhancing and suppressing activities of AMLR-activated T cells were mediated by an la-positive and radiosensitive population within the OKT4+ subset. These observations suggest that AMLR-activated T cells may play a role in the immune-mediated regulation of in vitro erythropoiesis. It is also suggested that heterogeneous T-cell subsets may exert regulatory functions in the regulation of in vitro hematopoiesis.

Antibodies, Monoclonal↗

[Concomitant therapy with cefmenoxime and cefsulodin for refractory complicated urinary tract infection (especially caused by Pseudomonas aeruginosa)].

Cefmenoxime (2 g) and cefsulodin (1 g) were given twice daily for 5 days by concomitant intravenous drip infusion (mixed infusion) to 135 patients with complicated urinary tract infection (c-UTI) probably caused by Pseudomonas aeruginosa. The clinical efficacy was evaluated according to the criteria proposed by the UTI committee in Japan. Ninety one subjects met the criteria for c-UTI and were evaluable for drug efficacy. P. aeruginosa was detected in 44 cases (including mixed infection with other organisms). The overall efficacy rate was 73% of the 91 cases; 75% of the 44 cases with P. aeruginosa and 70% in the 47 cases without P. aeruginosa infection. As to bacteriological response, the eradication rate was 91% (105/116) for all cases. By organism, the eradication rate for P. aeruginosa, Serratia spp. and Citrobacter spp. were 82 (36/44), 100 (12/12) and 100% (10/10), respectively. The eradication rate for gram-negative rods was 93% (99/107). Twenty-three strains appeared after treatment, and the majority of them (13) were yeast-like organisms. There was only one strain of P. aeruginosa. As for side effects, eruption was found in 2 cases. Cefmenoxime and cefsulodin were administered concomitantly to patients with c-UTI which was suspected to be caused by P. aeruginosa. The high overall efficacy rate of about 70% on the average was obtained regardless of the causative organism and disease state. The eradication rate of as high as about 90% was obtained excluding Enterococcus faecalis. Neither severe side effects nor abnormal laboratory values were found. It appeared, therefore, that this dosage regimen was useful for the treatment of refractory complicated urinary tract infection.

Anti-Infective Agents, Urinary↗

[Indications for aortocoronary bypass operation in elderly patients: medical point of view].

Aorto-coronary (A-C) bypass operations were performed in 20 patients aged 68 to 78 years, and the indications for this operation were discussed retrospectively. The subjects consisted of 14 patients successfully operated and six patients unsuccessfully operated (death 3, graft occlusion 2, perioperative infarction 1). The results were as follows: Average age: There was no difference between the successful group (71.1 +/- 3.3 years; mean +/- SD) and the unsuccessful group (70.3 +/- 2.9 years). Coronary arteriographic findings: The average number of narrowed branches (greater than or equal to 75% stenosis) was 4.3 +/- 3.0 in the successful group (triple vessel disease in 12 cases and double vessel disease in four) and 2.7 +/- 0.5 in the unsuccessful group (triple vessel disease in four and double vessel disease in two), showing no significant difference between the two groups. Nine patients (64.3%) in the former group and one (16.7%) in the latter group had significant left main coronary artery disease (greater than or equal to 50% stenosis). Hemodynamic findings: Ejection fractions of less than 40% existed in three patients (50%) solely in the unsuccessful group; two of whom died. Left ventricular end-diastolic pressures of 30 mmHg or more existed in two cases (33.3%) only in the latter group. Other cardiac findings: Left ventricular end-diastolic dimension of 55 mm or more was found in one (7.1%) successful case and four (66.7%) unsuccessful cases. 201Tl-scintigrams showed a dilated left ventricular cavity in one case (7.1%) in the former group and two (33.3%) in the latter. Functions of other organs: Forced expiratory volume 1.0% or % vital capacity less than 70% was recognized in two cases (33.3%) only in the latter group. A level of serum creatinine more than 1.5 mg/dl was seen in only one case in the latter group. A case with advanced diabetes mellitus was present in the unsuccessful group, and this patient died of diabetic coma. A-C bypass operations are indicated for elderly patients when they have good cardiac function and have no complications of the kidneys, lungs and other organs. It is presumed that grafting the main coronary branches, thereby shortening the time of cardiopulmonary arrest prevents postoperative complications.

Aged↗

Coordinate repression of arginine aminopeptidase and three enzymes of the arginine deiminase pathway in Streptococcus mitis.

Streptococcus mitis contains two arginine aminopeptidases (I and II) as an arginine-supplying system and the arginine deiminase pathway as an arginine-utilizing system. The levels of arginine aminopeptidase I and three enzymes of the arginine deiminase pathway were suppressed by glucose in an apparently coordinate manner. Enzyme II appeared to be constitutive.

Aminopeptidases↗