Search PubMed⌕ Search

Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

At least 397 records · Page 22Linked to original sources

Level of translatable messenger RNA coding for argininosuccinate synthetase in the liver of the patients with quantitative-type citrullinemia.

The translation activity of mRNA coding for argininosuccinate synthetase in total RNA extracted from the liver of three patients with quantitative-type citrullinemia was determined using a cell-free translation system. In two patients, the hepatic content of the enzyme was about 20% of the control value, whereas translatable mRNA level for the enzyme was similar to or slightly lower than those of control livers. In the third patient, the enzyme content was about 50% of the control value, and mRNA activity for the enzyme was low normal. These results indicate that at least in the first two patients, the decrease in the enzyme protein is due either to increased degradation of the enzyme or to decreased translation in the patient's liver.

Adult↗

Effects of tris(hydroxymethyl)aminomethane on biosynthesis and release of insulin in the pancreatic Langerhans islets.

Tris(hydroxymethyl)aminomethane (Tris) has been shown to inhibit selectively the Golgi apparatus and Golgi-endoplasmic reticulum-lysosomal system (GERL system) of several kinds of cells including pancreatic B cells. This study was designed to assess the effect of Tris on insulin, glucagon and somatostatin release and insulin synthesis in pancreatic B cells by using isolated rat pancreatic islets. Tris suppressed glucose-induced insulin release, whereas it did not affect the glucagon and somatostatin release. Furthermore, the incorporation of [3H]leucine into the insulin fraction was suppressed by 10 mM Tris, but the sum of the radioactivity of both proinsulin and insulin fraction were not influenced. The present study suggests that the Golgi apparatus and GERL system may play a role in insulin secretion and biosynthesis in pancreatic B cells.

Animals↗

[Clinical trial of 5'-deoxy-5-fluorouridine (5'-DFUR) in advanced cancer patients].

5'-DFUR was administered orally to advanced or recurrent cancer patients at a daily dosage of 600-1200 mg divided into 3 or 4 times a day. Out of 13 evaluable cases 2PR, 2MR, 4NC and 5PD were observed, response rate was 15.4%. PR were obtained in one gastric cancer case and one breast cancer case. Side effects were observed in 6 cases out of 14 cases (42.9%) and major adverse reaction was gastro-intestinal toxicities such as anorexia, nausea-vomiting and diarrhea. Two leukocytopenia and one erythrocytopenia were observed. This study indicated that 5'-DFUR would be useful as a new anticancer agent.

Aged↗

[Phase I trial of 4'-O-tetrahydropyranyl-doxorubicin (THP)--a multi-institutional cooperative study].

A phase I trial of a new anthracycline derivative, 4'-O-tetrahydropyranyldoxorubicin (THP), was conducted in 54 patients with various advanced solid tumors and malignant lymphomas. Starting dose was 5 mg/m2 i.v. and dose escalations were made by a modified Fibonacci search scheme. There were 40 evaluable courses. The dose-limiting toxic effect was leukopenia which was dose-related and reversible. The maximum tolerated dose for a single i.v. injection was estimated to be 55 mg/m2. The median nadir day for leukopenia was day 12 with recovery occurring 13 days (median) after reaching the nadir. Thrombocytopenia was less commonly observed than leukopenia. Other toxic effects were mild gastrointestinal disturbances, fever and general malaise. Ventricular extrasystole was observed in a case of pancreatic cancer who received 5 mg/m2 of the drug. There were no cases with alopecia, or with hepatic or renal dysfunction. With regard to objective tumor response, CR was observed in 2 cases with NHL, and MR in 2 cases with lung cancer, and 1 case each with breast cancer and NHL. Response occurred at a dose of more than 35 mg/m2. The recommended dose schedule for phase II trial is 35-45 mg/m2 by single i.v. injection at 3-4-week intervals.

Aged↗

Treatment of multiple myeloma with recombinant human leukocyte A interferon.

A phase II study of recombinant human leukocyte A interferon was conducted in 64 patients with multiple myeloma in a multi-institutional cooperative trial. Partial remission was achieved in ten (21.3%) of 47 evaluable patients and minor response was observed in five (10.6%). Side effects were noted in more than two-thirds of the patients. They included fever (58%), malaise (20%), anorexia (52%), nausea and vomiting (26%), lethargy (2%), and myelosuppression (56%). An antibody to recombinant human leukocyte A interferon was detected in one of 20 patients.

Adult↗

Highly potent and specific inhibitors of human renin.

We designed aldehyde derivatives of small peptides representing the C-terminal portion of angiotensin I sequence as an inhibitor of human renin. Among compounds that we synthesized, benzyloxycarbonyl (Z)-Phe-His-Leucinal (compound V), Z-Pro-Phe-His-Leucinal (Compound IV) and Z-[3-(1'-naphthyl)Ala]-His-Leucinal (compound VII) markedly inhibited human renin (IC50, 7.5 X 10(-7), 3.2 X 10(-7) and 8.0 X 10(-8) mol/l, respectively). Compound VII was shown to be noncompetitive (Ki = 2.4 X 10(-7) mol/l). It did not inhibit either cathepsin D or pepsin. Compound V had slight or no inhibitory effect at the concentration of 10(-5) mol/l on six animal renins except for monkey and rabbit renins. Results obtained show that these aldehyde compounds are highly selective and species specific inhibitors for human and monkey renins.

Aldehydes↗

[Insulin degrading system on isolated rat hepatocytes; enzymatic and immunologic characteristics of insulin-degrading activities].

Insulin degradation by isolated rat hepatocytes was investigated. Using the preincubation method, the extracellular insulin-degrading activity was removed from the medium over 120 min at 15 degrees C and 60 min at 37 degrees C. The degradation of insulin was assayed by the ability of binding to specific receptors on isolated rat hepatocytes (rebound method) and the precipitability with trichloroacetic acid (TCA method). The degrading activities measured by the rebound method showed twice those by the TCA method, however, a positive correlation with high coefficient (r = 0.87, P less than 0.001) was demonstrated between both methods. The insulin-degrading activity by hepatocytes depended on time, temperature and cell concentrations, and the optimum pH was 7.0. As a result of kinetic analysis of insulin binding and degradation, the degradation velocity of 125I-insulin was inhibited by 50% at native insulin concentration of 7 X 10(-8) M, whereas the half-maximum inhibition of 125I-insulin binding was demonstrated at that of 4 X 10(-9) M. The Km for insulin degradation was 170 nM. In order to characterize the enzymatic properties of insulin-degrading activity by isolated hepatocytes, the effects of various compounds and anti-insulin-degrading enzyme (IDE) rabbit serum on insulin degradation were examined. N-ethylmaleimide and anti-IDE serum significantly inhibited the insulin-degrading activity, while dithiothreitol stimulated it, whereas chloroquine and NH4Cl had little effect on insulin-degrading activity. Finally, the immunoenzymatic labelling of hepatocytes by anti-IDE serum showed the presence of cell surface IDE on isolated hepatocytes. These results suggest that most of insulin-degrading activity by isolated rat hepatocytes is identical to pig muscle IDE. Therefore, it would seem that IDE plays an important role in insulin metabolism by isolated rat hepatocytes rather than lysosomes.

Animals↗