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R Yajima

Publications and source records attributed to R Yajima.

29 records · Page 2Linked to original sources

Secretion of peptidylglycine alpha-amidating monooxygenase (PAM) from rat salivary glands.

Peptidylglycine alpha-amidating monooxygenase (PAM) is a regulating enzyme to synthesize the biologically active hormones having carboxy-terminal amide. In the present study we investigated secretion of the enzyme from rat saliva. Property of PAM in the saliva was similar to that in the submandibular gland. Both enzymes showed similar pH optimum at 5.0 and optimal ascorbic acid concentration at 2.5 mM. But molecular size of PAM in the saliva was 75 kDa in the gel permeation chromatography on Superose 12 column, while the size in the submandibular gland was 25 kDa. After the treatment with trypsin, PAM in the saliva was converted to a small size molecule, which is similar to the size in rat submandibular gland. These and other data indicate that a native molecular size of PAM is secreted into saliva and plays some physiological roles.

Aging↗

Anterograde axonal transport of peptidylglycine alpha-amidating monooxygenase in rat sciatic nerves.

Axonal transport of peptidylglycine alpha-amidating monooxygenase (PAM) activity was studied in rat sciatic nerves from 12 to 120 h after double ligations. The anterograde axonal transport increased and reached a plateau between 48 and 72 h and then decreased. The flow rate was 100 mm/day, and the molecular mass of the active entity was 70 kDa, which was determined by gel filtration. In contrast, there was no evidence for significant retrograde axonal transport. Anterograde axonal transport of immunoreactive cholecystokinin, a carboxy-terminal-amidated putative neuropeptide, was also found. These results suggest that PAM is transported by a rapid axonal flow and may play a role as a processing enzyme during transport or in the terminals of rat sciatic nerves.

Animals↗

[Local irritancy study of cefpirome sulfate].

As a series of safety studies of cefpirome sulfate (CPR), its local irritancy was examined in rabbits after the following treatments: intracutaneous injection (single), application into the conjunctival sac of the eye (single), intramuscular injection (single, 7-day repeated), and intravenous injection (8-day repeated). In addition, the hemolysis test was carried out with human blood. When CPR was injected intracutaneously at a high concentration of 20%, its irritating effects were only equal to or slightly stronger than those of distilled water for injection and Na2SO4 solution. The same concentration of the compound applied into the conjunctival sac had little irritancy to the eye. In the single intramuscular administration experiment, muscular changes caused by 10% CPR were comparable to those by 0.75% acetic acid, slightly severer than those by physiological saline, and slighter than those by 6% acetic acid at 2 days after administration, but at 7 days, the changes were apparently slighter than those by 0.75% acetic acid. CPR is classified under Grade 3 according to the draft guidelines for local tolerability studies issued by the Ministry of Health and Welfare of Japan. The repeated intramuscular administration experiment showed the following results. Muscular changes caused by 10% CPR were comparable to those by physiological saline and slighter than those by 0.75% acetic acid, 5% cefotetan (CTT) and 20% cephalothin sodium (CET) at 2 days after the last administration. At 7 days, the changes were slightly severer than those by physiological saline, but slighter than those by the other control solutions. Microscopically, a tendency toward recovery was marked. In the vascular irritancy experiment, the 10% CPR group showed thrombus macroscopically on and after day 5 of dosing. Microscopy at the end of the 8-day administration period revealed thrombus and organized thrombus. In the 20% CET group, thrombogenesis was slighter than that in the 10% CPR group, while perivascular changes were severer. The changes caused by 5% CTT (thrombogenesis, perivascular changes) were somewhat severer than those by 10% CPR. In the hemolysis test, 10% CPR solution applied to fresh blood from adult men caused to hemolysis when determined by the macroscopic or spectrophotometric method.

Animals↗

[One-month subacute intravenous toxicity study of cefodizime sodium in rats].

One-month subacute intravenous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 2000, 1000 and 500 mg/kg/day. Sixteen males and 16 females were used per group (including the control group). THR-221 caused neither death nor change in general conditions at any dose level throughout the study, except that decreased spontaneous activity appeared only transiently in a part of the animals given 2000 mg/kg/day. Increases in water intake were observed in all compound groups, and transient decreases in food consumption were seen at an early stage of the administration period. However, the compound did not affect the body weight at any dose level. In urinalysis, the urine sediments in all THR-221 groups contained an increased number of epithelial cells as compared with the controls. At autopsy, dilation of the cecum was observed in all THR-221 groups, and in a part of the rats with this change, red spots or reddening of the serous membrane of the organ also appeared. Light microscopy revealed brown granules in the epithelium of renal tubules in all compound groups (with dose-dependent incidences) and congestion or hemorrhage in the cecum in some compound-treated animals. Electron microscopy on the kidney showed small bodies (considered to be lysosomes) in the tubular epithelium in all compound groups. No other changes related to THR-221 were observed. From the present results that no marked toxic signs were seen at any dose level, the toxicologically non-effective dose of THR-221 for rats of both sexes is considered to be more than 2000 mg/kg/day.

Animals↗

[Effect of cefodizime sodium on the kidney function in male rabbits--single and 7-day repeated intravenous administration].

Renal effects of cefodizime sodium (THR-221) administered by the intravenous route singly and for 7 consecutive days to male rabbits, were compared with those of cefazolin sodium (CEZ) and cephalothin sodium (CET). Four animals were used in each group including control groups. In the single-dose study, THR-221 (600 and 1800 mg/kg) and CET (1800 mg/kg) caused no nephrotoxic effects. In the CEZ groups (600 and 1800 mg/kg), findings indicative of the decreased renal function were obtained: serum urea nitrogen and creatinine levels increased over the control values, and phenolsulfonphthalein (PSP) retention test showed a delay in PSP excretion from the blood. In addition, the white surface of the kidney was macroscopically observed, and microscopic examination revealed renal proximal tubular changes such as necrosis, hyaline cast and calcification, suggesting renal disorders. The repeated-dose study also showed similar results to those described above. Administration of THR-221 (200 and 600 mg/kg/day) and CET (600 mg/kg/day) caused no effects on the kidney. In the CEZ groups (200 and 600 mg/kg/day), serum chemical and PSP test results suggested the decreased renal function, and macroscopic and microscopic findings included organic changes in the kidney. These results suggest that under the conditions tested THR-221 dose not elicit signs of nephrotoxicity in contrast to CEZ, and behaves almost equally to CET.

Animals↗

[Six-month chronic subcutaneous toxicity study of cefodizime sodium in rats].

Six-month chronic subcutaneous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 3000, 1000, 300 and 100 mg/kg/day. The systemic change observed was slightly decreased spontaneous activity, which appeared only in a very few animals. At the injection site of the animals at 1000 and 3000 mg/kg/day, various cutaneous changes (subcutaneous retention of fluid, incrustation, loss of hair and perforation) were observed. The body weight gains of the males at 1000 and 3000 mg/kg/day were depressed from 1 month of administration onward, but the food consumption was not affected in any group. The water intakes at 1000 and 3000 mg/kg/day were increased. Hematological findings were signs of anemia, a slight decrease in red blood cell count or increases in platelet and/or reticulocyte counts in all THR-221 groups. At 3000 mg/kg/day, increases in white blood cell and neutrophil counts and a decrease in lymphocyte count were also observed. Plasma chemistry revealed decreases in total protein amount and, albumin (A) or globulin (G) amounts, and a decrease or increase in A/G ratio in all compound groups. Autopsy revealed dilation of the cecum and hematoma, dark red spots and yellowish brown spots in the subcutaneous tissue at the injection site in all THR-221 groups. Hypertrophy of the spleen was also noted at 300-3000 mg/kg/day. Changes in organ weights were a decrease in liver weight in all compound groups and an increase in spleen weight at 3000 mg/kg/day. Microscopically, the following were observed: brown granules or hyaline droplets in the epithelium of renal tubules; hemorrhage and inflammatory changes in the subcutaneous tissue at the injection site; and an increased number of lymphocytes or granulocytes in the spleen and bone marrow. Urinalysis and ocular and auditory tests showed no changes related to THR-221. From the present results, the toxicologically non-effective doses of THR-221 are considered to be 300 mg/kg/day for male rats and more than 1000 mg/kg/day for female rats.

Anemia↗

[A micro-method developed for prothrombin time assay (author's transl)].

Prothrombin time was measured by a newly developed micro-method using a plastic film available in the market (PARAFILM, American Can. Co.). The comparative study of this micro-method with that of Quick in rats disclosed a good correlation, with correlation coefficient of 0.951, supporting the usefulness of the method for examination of blood coagulability. The new method gave the physiological values of 9.8 sec in rabbits, 12.5 sec in dogs, 13.3 sec in mice, 14.8 sec in cats and 16.0 sec in rats, respectively. Among them, guinea pigs took the longest time of 25.3 sec for the coagulation.

Animals↗