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Biomedical subjects

M Omori

Publications and source records attributed to M Omori.

At least 91 records · Page 5Linked to original sources

[General pharmacology of T-1982, a new cephamycin antibiotic].

General pharmacological studies on T-1982 produced the following results. On central nervous system, subcutaneous injection of T-1982 at dose of 2,000 mg/kg hastened the onset of pentetrazole-induced tonic extensor in mice. T-1982 had no effect on spontaneous motor activity, pentobarbital hypnosis, body temperature or EEG in mice or rabbits, and also did not show motor incoordinate, anticonvulsive or analgesic activity in mice at intravenous doses of 250--1,000 mg/kg or subcutaneous doses of 500--2,000 mg/kg. On motor and sensory nervous systems, no effect of T-1982 was noted on spinal reflex, neuromuscular junction, conduction anesthesia or surface anesthesia in rats or rabbits. On respiratory, cardiovascular and autonomic nervous systems, T-1982 caused transient increase of respiratory rate, slight hypotension and transient increase of femoral blood flow in dogs at intravenous doses of 250--1,000 mg/kg. However, it caused a slight hypertensive tendency in rabbits. Heart rate and ECG in dogs or rabbits, blood pressure response to epinephrine, isoproterenol, acetylcholine or histamine in dogs, nictitating membrane in cats and pupil size in mice were not affected after intravenous injection of T-1982. No effect was found on isolated guinea pig atrium or rabbit descending aorta following T-1982 application. On renal function in rats, T-1982 caused an increase of PSP excretion but had no effect on urine volume or electrolytes excretion at intravenous doses of 250--1,000 mg/kg. T-1982 prolonged bleeding time in mice at intravenous doses of 500--1,000 mg/kg, but did not show hemolytic property and inhibitory activity on blood coagulation or platelet aggregation in vitro experiments. Spontaneous movement and tone of isolated stomach, ileum, colon, uterus, vas deferens or trachea and acetylcholine-, histamine-, nicotine- or barium chloride-induced contraction of ileum were not affected following T-1982 application. Intestinal propulsion of barium meal in mice, gastric secretion and carrageenin-induced edema in rats were not affected after intravenous injection of T-1982. T-1982 increased bile secretion in rats dose-dependently at intravenous doses of 31.3--125 mg/kg. The local irritative activity of T-1982 in rats was slightly milder than cefoxitin and moderately milder than cefmetazole after intradermal injection. In conclusion, these results suggest that T-1982 would not cause any adverse effects at its estimated clinical doses of 10--20 mg/kg (500--1,000 mg/man).

Animals↗

Cellular retinoid-binding proteins in reginerating rat liver: demonstration of a novel cellular retinoid-binding protein.

Changes in the levels of liver cellular aetinol- and retinoic acid-binding proteins were studied after partial (about 70%) hepatectomy for 14 days in the rat. It was found that a novel binding protein designated F-type appears transiently in liver cytosol 3 days after the operation. The appearance of this protein coincides with the peak level of the alpha 1-fetoproteain. In contrast, cellular retinoic acid-binding protein was detected only the first day after hepatectomy, whereas no significant change was observed in the level of the cellular retinol-binding protein during the entire observation period. [3H]Retinol or [3H]retinoic acid complexed with serum retinol-binding protein injected intravenously into vitamin A-deficient rats 1 day after the hepatectomy was recovered 5 min or 20 min later bound specifically to cellular retinol- or retinoic acid-binding protein, respectively. The results presented here strongly suggest that each of the three cellular retinoid-binding proteins plays a distinct role in cell proliferation and differentiation.

Animals↗

In vitro binding affinity of novel synthetic polyprenoids (polyprenoic acids) to cellular retinoid-binding proteins.

A study was conducted to investigate the in vitro binding affinity of new synthetic polyprenoids to cellular retinoid-binding proteins. Among 10 synthetic polyprenoic acid derivatives, 3,7,11,15-tetramethyl-2,4,6,10,14 hexadecapentaenoic acid (compound 1) was found to have the strongest binding affinity to cellular retinoic acid-binding protein (CRABP) from rat testis. As regards the chemical structure of the polyprenoic acids, it was found that suitable carbon chain length and double bond arrangement are both essential for binding affinity to CRABP. Moreover, compound I displayed a binding affinity to cellular retinoid receptors obtained from precancerous tissues such as mouse skin papillomas and rat liver hyperplastic nodules experimentally induced.

Animals↗

[General pharmacology of cefoperazone, a new cephalosporin antibiotic (author's transl)].

General pharmacological properties of cefoperazone (CPZ) were studied in various experimental animals. CPZ showed the following effects with intravenous injection to experimental animals. On the central nervous system, CPZ caused vomiting in dogs at 500 mg/kg, pyrexia and slow waves in electroencephalogram in rabbits at 1,000 mg/kg. On the motor and sensory nervous systems, CPZ enhanced slightly the twitch tension of musculus gastrocnemius induced by electrical stimulation in rats at 500 mg/kg. On the respiratory, cardiovascular and autonomic nervous systems, CPZ increased transiently the respiratory rate and potentiated the depressor response to Ach at 125 mg/kg, increased femoral blood flow, potentiated the pressor response to Adr in dogs and decreased the contraction of nictitating membrane induced by electrical stimulation in cats at 500 mg/kg, and then raised the systolic blood pressure in rabbits at 1,000 mg/kg. On the blood, CPZ decreased ChE activity in rabbit plasma at 250 mg/kg, prolonged bleeding time in mice at 500 mg/kg and prothrombin time in rabbits at 1,000 mg/kg. On the smooth muscle organs, CPZ enhanced slightly gastric motility in rabbits and ileal motility in guinea pigs at 62.5 and 125 mg/kg respectively, and promoted gastrointestinal propulsion of BaSO4 meal in mice at 1,000 mg/kg. On the urinary organ, CPZ increased urine volume and electrolytes excretion in dogs at 500 mg/kg. Subcutaneous injection of CPZ scarcely showed any significant effect in experimental animals under the dose of 2,000 mg/kg. In the in vitro experiments, CPZ enhanced slightly the motility of isolated rabbit gastrointestinal tract at 10(-3) g/ml. Assuming the single clinical dose of CPZ should be 10 approximately 40 mg/kg, it is concluded that the occurrence of pharmacological effects observed in experimental animals seems to be very rare clinically.

Animals↗

Demonstration of a novel molecular species in chick embryo brain: cellular retinol-binding protein, F-type.

By sucrose density gradient sedimentation analysis, a cytosol component of small molecular size which bound 3H-retinoic acid was detected in the chick embryo brain, exhibiting a peak on day 14 (7 days before hatching). In general, cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) have been distinguished by showing binding specificity for retinol or retinoic acid, respectively. However, the component found in embryo brain cytosol exhibited binding affinity for both retinol and retinoic acid, being similar in less ligand-specificity to CRBP (F) which was originally recognized in fish eye cytosol. Moreover, the component also showed a lack of binding affinity for prealbumin (PA), excluding the possibility that chicken plasma RBP was contaminated in the cytosol. These findings strongly suggest that a distinct molecular species of cellular binding protein for vitamin A exists in the brain cytosol of a developing chick embryo.

Animals↗

Demonstration of a novel cellular retinol-binding protein, F-type, in hepatocellular carcinoma.

Vitamin A level and the cytosol-binding proteins specific for vitamin A ere studied in human tumor and its surrounding tissue. The tissues examined were 10 hepatocellular carcinomas which were surgically removed, 4 other malignant tumors (2 metastatic liver cancer and one each of gastric cancer and glioma), and 3 human fetal livers. Compared with surrounding tissues, considerable decrease of vitamin A content was observed in the hepatocellular carcinoma suggesting local deficient state of the vitamin. In addition to cellular retinol-binding protein (CRBP) and retinoic acid-binding protein (CRABP), a new molecular species having affinity for both retinol and retinoic acid was detected in the cytosols obtained from hepatocellular carcinoma as well as glioma by means of gel filtration on Sephadex G-75. With regard to ligand specificity, the protein was found to be similar to cellular retinol-binding protein, F-type or CRBP(F) which was originally recognized in the fish eye cytosol. Since the protein was also demonstrated in human fetal liver, CRBP(F) is considered to be an oncofetal protein in nature. The present study further revealed that CRBP(F) was detected in 80% of hepatocellular carcinoma (whereas plasma alpha-fetoprotein was significantly elevated only in 50%), and hepatocellular carcinoma contained CRBP(F) in a larger amount than CRABP.

Adult↗