Studies on the biosynthesis of carbapenem antibiotics. III. Enzymological characterization of the L-amino acid acylase activity of A933 acylase

A933 acylase, which is involved in exchange of the pantothenyl substituent of OA-6129 carbapenems with acetyl CoA, was characterized as an L-amino acid acylase with a molecular weight of 100,000 (+/- 8,000) and a pI value of 5.1. The highest L-amino acid acylase activity of A933 acylase was observed at 37 degrees C and pH 7 approximately 7.5 for N-chloroacetyl-L-phenylalanine. Unlike other amino acid acylases, A933 acylase was severely inhibited by cobalt ions and p-chloromercuribenzoate. The acylase also showed peptidase activity with some di- and tripeptides. A protein fraction with A933 L-amino acid acylase activity from blocked mutant 1501 lacked OA-6129A-depantothenylating activity.     

A phase III trial of oral high-dose medroxyprogesterone acetate (MPA) versus mepitiostane in advanced postmenopausal breast cancer

A randomized controlled trial was performed to compare the therapeutic results of oral high-dose medroxyprogesterone acetate (HD-MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA was given at three doses of 400 mg orally daily to 47 patients and produced objective responses in 19 cases (40.4%). An objective response was seen in 14 of the 40 control patients given MS at two doses of 10 mg orally daily (35.0%). Among patients with bone metastases, 6 of 19 (31.6%) for HD-MPA and 2 of 13 (15.4%) for MS showed objective responses. The other merits of HD-MPA suggested in the study were improvement in performance status, increase in appetite, and myeloprotective effect.     

Clinical investigation of oral high-dose medroxyprogesterone acetate (MPA) in advanced breast cancer--double-blind controlled study: Japanese Group for MPA Treatment of Breast Cancer

A randomized controlled trial was made to compare the therapeutic result of oral high-dose medroxyprogesterone acetate (HD-MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA (1200 mg) was given p.o., b.i.d. to 47 patients and produced objective response in 19 of them (40.4%). Objective response was seen in 14 of the 40 control patients given MS p.o., b.i.d. (35.0%). Among patients with bone metastases, 6/19 (31.6%) for HD-MPA and 2/23 (15.4%) for MS showed objective response. The other merits of HD-MPA suggested in the study were improvement in performance status, anabolic effect and myeloprotective effect.     

Effects of S-adenosyl-L-methionine upon ischemia-induced brain edema in Mongolian gerbils and spontaneously hypertensive rats

Effects of S-adenosyl-L-methionine (SAMe).2 sulphate.tosylate upon the ischemia-induced brain edema and survival rate in Mongolian gerbils and spontaneously hypertensive rats were investigated, since SAMe is known to be important as a physiologically active substance in numerous metabolic processes including those that are inhibited in ischemia. SAMe suppressed increases in water and Na+ content in the ischemic brain which was produced by ligation of the common carotid artery for a short term (20-30 min) in Mongolian gerbils. This ameliorating effect of SAMe was observed dose-dependently at higher doses than 100 mg/kg administered repeatedly every 0.5 or 1 hr, starting within 2 hr, at least, after the reperfusion. Similar effects were also obtained in spontaneously hypertensive rats whose common carotid artery on both sides were ligated permanently. SAMe also increased survival rate in Mongolian gerbils with ischemic brain. Although the SAMe solution employed in the present experiments was hypertonic and contained mannitol as a filler, the beneficial effects were due to neither the hypertonicity of the solution nor mannitol, but due to SAMe itself.     

Experimental gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats

MNNG-induced experimental gastric cancer developed in the pyloric glandular region. Many of the tumors produced were well or moderately differentiated adenocarcinomas of elevated type. According to the degree of depth invasion, a majority of the tumors were classified as early-stage lesions invading within submucosal layer. There were two poorly differentiated lesions, which were both recognized as serosal neoplastic involvements. The tumors were positively stained by toluidine blue (pH 4.1) to indicate the presence of stroma. The Brdu-LI determined for gastric mucosal epithelial cells was significantly higher in the MNNG-treated group than in the untreated control group. However, the LI for cancer tissue in the MNNG-treated group did not significantly differ from that for gastric mucosa in the same group.     

Inhibition by anti-beta2-microglobulin antisera of responder cells and not of stimulator cells in the mixed lymphocyte reaction.

Specific antisera directed against beta2-microglobulin (B2m) have been shown to inhibit completely the mixed lymphocyte reaction (MLR). However, the mechanism of inhibition has been unclear. In the present study, further experiments were performed to determine the effect of anti-B2m on both the stimulator and responder cells in an MLR. The experimental design used was that of a xenogeneic MLR, using mouse and human lymphocytes. The ffect of anti-human B2m was studied in this system. Anti-human B2m inhibited the xenogeneic MLR only when human lymphocytes were used as responder cells and did not inhibit the MLR when they were used as stimulator cells...