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Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 487 records · Page 27Linked to original sources
PubMed1989

[Pharmacological studies of a non-steroidal analgesic and antipyretic drug of LFP83].

Pharmacological properties of LFP83, a non-steroidal analgesic and antipyretic drug, were studied in mice, rats and rabbits. LFP83 is a prodrug of flurbiprofen (FP) which is its active major metabolite in vivo. In experimental models of acetic acid writhing, the Randall and Selitto method, arthritic pain, yeast fever, LPS fever, carrageenin edema and adjuvant arthritis, LFP83 (i.v.) showed remarkable analgesic, antipyretic and antiinflammatory activities; and it was more potent than ketoprofen (i.m.) and aspirin DL-lysine (i.v.). The analgesic activity of LFP83 was equal to or more potent than that of pentazocine, and its duration was longer than those of aspirin DL-lysine and pentazocine. In addition, the analgesic potency of LFP83 was approximately the same or more potent than that of FP (p.o.), and the onset of this analgesic effect began earlier. On the other hand, the ulcerogenic activity of LFP83 on rat gastric mucosa was less than that of FP (p.o.) in both single and consecutive (7 days) administrations. The safety index (UD50/ED50) of LFP83 was three to ten-fold higher than that of FP (p.o.). As mentioned above, LFP83 is a potent analgesic, antipyretic and antiinflammatory drug; and in comparison to oral FP, it has a more potent and immediate effect, weak gastric irritation and high safety index.

Analgesics↗
PubMed1989

Effects of chronic hypokalemia on ventricular vulnerability during acute myocardial ischemia in the dog.

Chronic hypokalemia (2.9 +/- 0.2 mEq/L) was induced in 10 dogs by a low potassium diet and furosemide administration. Five control dogs with normokalemia (5.0 +/- 0.3 mEq/L) were fed an ordinary diet. Three of the 10 hypokalemic dogs had electrically induced, nonsustained ventricular tachycardia (NSVT) and ventricular fibrillation (VF); none of the 5 control dogs had these ventricular arrhythmias. After ligation of the left anterior descending coronary artery (LAD), 4 of the 10 hypokalemic dogs developed spontaneous VF and 6 had electrically induced NSVT and VF, whereas 2 of the 5 control dogs had only NSVT. The effective refractory period (ERP) of the ventricles of the hypokalemic dogs was slightly longer than that of the control dogs. After LAD ligation, only the ERP of the anterior wall of the left ventricle was prolonged significantly in either group (p less than 0.01). The ventricular fibrillation threshold (VFT) of hypokalemic dogs was significantly lower than the control dogs (p less than 0.05), and was reduced markedly (p less than 0.05) after LAD ligation. A positive correlation between VFT and serum potassium level was observed. Thus, chronic hypokalemia increases ventricular vulnerability. This effect depends upon the severity of hypokalemia and is markedly augmented by acute myocardial ischemia. These findings indicate that, in clinical settings, preexisting hypokalemia and its severity may play important roles in the occurrence of lethal ventricular arrhythmias during the acute phase of myocardial infarction.

Acute Disease↗
PubMed1989

Separation and quantification of serum alkaline phosphatase isozymes in the rat by affinity electrophoresis.

The purpose of this study was to examine the possibility of separation and quantification of serum alkaline phosphatase (ALP) isozymes in rats by wheatgerm lectin affinity electrophoresis. Cellulose acetate electrophoresis of the liver and bone ALPs without lectin results in overlapping bands, but in the presence of lectin, the mobility of the band of bone enzyme was retarded and well separated from the liver enzyme band. With this affinity electrophoretic method, we determined the serum ALP isozymes in fed and fasting rats grouped by age. As a result, the absolute activity of bone isozyme showed a downward trend with age in the fed and fasting rats. The serum ALP activity was steadily higher in fed rats than in fasting rats, and the increase was due to intestinal ALP isozyme. There was low activity bordering complete absence in liver isozyme under both nutritional conditions. The affinity electrophoretic method provided a rapid, reproducible, and relatively simple technique for further clinical characterization of ALP isozyme in the rat serum.

Alkaline Phosphatase↗
PubMed1989

[Biochemical characterization of calf sera used in the maintenance of cell cultures used in virology].

Eight lots of the calf sera employed to supplement culture media for the cultivation of animal cells, of widespread use in virology obtained from calves above and below six months of age were rated as good or as poor cell growth promoters according to their growth promoting capacity (GPC). Parameters related to macronutrients contained in these serum lots were then evaluated with the purpose of establishing their biochemical profiles. The results obtained can be considered as normal values for apparently healthy animal donors. Fluctuations found between the data of this investigation and those mentioned in the literature for certain biochemical parameters are probably due to the methodology employed, the breed and age of the animals, or even to regional diet. Student's "t" test was applied for the statistical analysis of the results and demonstrated that, as far as serum fractions were concerned, no significant differences occurred between sera rated as good and poor cell growth promoters, taking tc = 2.45. For calf sera from animals above and below six months of age, two tests relating to alfa and beta fractions were significant (t = 2.68 and 2.61 respectively). It was demonstrated that the evaluation of the biochemical parameters mentioned "per se" neither leads to the identification of calf sera presenting good or poor GPC, nor of sera harvested from calves younger or older than six months.

Animals↗
PubMed1989

[Study on determination of the imaginary axis of the tooth crown. 1. Measuring procedure].

The state of inclination and the change under various conditions of the imaginary axis of the tooth crown of upper jaw and lower jaw right and left first molar can be determined by the measuring apparatus and method of this study. 2. The measurement error of this method was not more than 0.1 degree. This value was sufficient for the purpose of this study.

Molar↗
PubMed1989

Sparganosis of the brain. Case report.

A rare case of cerebral sparganosis occurring in a 7-year-old boy is reported. Since his clinical symptoms fluctuated and diagnostic evaluation demonstrated multiple lesions, he was examined for a parasitic infection. Emphasis is placed on the difficulties involved in diagnosing cerebral sparganosis.

Brain Diseases↗
PubMed1989

[Indications and results of non-shunting operations for esophageal varices].

Non-shunting operations were performed in 522 patients with esophagogastric varices in our department from January 1964 to March 1989. Transthoracoabdominal esophageal transection was performed in 287 patients (devascularization of the distal esophagus and the proximal half of the stomach and transection of the esophagus). Transthoracic esophageal transection was performed in 125 patients (31 Walker's transection, 94 esophageal transection with devascularization of distal esophagus). Transabdominal esophageal transection was performed in 49 patients. Hassab's operation was performed in 49 patients and three patients were treated with other direct operations (proximal gastrectomy, etc.) Overall mortality of non-shunting operation was 5.0%. The five year survival of idiopathic portal hypertension was 77.6%, extrahepatic portal obstruction was 90.7% and liver cirrhosis was 63.1%. Five year survival of Child's grade A was 79.8%, Child's grade B was 72.9% and Child's grade C was 38.6%. Operation on Child's C patients should be avoided since the results in these patients have been unsatisfactory. Our overall results with esophageal transection over the last two decades are satisfactory.

Adult↗
PubMed1989

[Study of impaired metabolism of guanidinoacetic acid in uremia--the compensatory role of the pancreas in guanidinoacetic acid synthesis].

We have already reported that renal glycine amidinotransferase (GAT) activity decreases in the course of renal damage, however, the inability of the kidney to synthesize guanidinoacetic acid (GAA) may be compensated by the pancreas in a more advanced stage of renal failure, and that in diabetes mellitus, the production of GAA is decreased from the period without renal dysfunction, and the extrarenal production of GAA is also decreased. In order to elucidate the significance of GAA synthesis in the pancreas, the author measured serum concentration of GAA, creatine, and the renal and pancreatic GAT activity in control, streptozotocin (STZ)-induced diabetic, insulin-treated diabetic, and ethionine-induced acute pancreatitis rats. The serum GAA concentration was depressed in untreated diabetic rats (21.5 +/- 2.5 micrograms/dl) compared with the level in controls (85.5 +/- 10.1 micrograms/dl), and was restored to control level by insulin treatment (66.2 +/- 7.3 micrograms/dl). The renal and pancreatic GAT activities were depressed in untreated diabetic rats compared with the level in controls and the latter was restored (625.2 +/- 96.2 micrograms/g.tissue/h) by insulin treatment. The positive correlation was observed between pancreatic GAT activity and serum GAA concentration. The serum GAA concentration was significantly higher in acute pancreatitis rats (716.0 +/- 223.7 micrograms/dl) compared with the level in controls, although the renal and pancreatic GAT activities were lower in acute pancreatitis rats compared with the level in controls. These results indicate that in STZ-induced diabetic rats, depressed pancreatic GAT activity was ameliorated by insulin treatment, consequently the level of serum GAA was restored and that GAA might be released from the acinar pancreas, resulting in higher concentration of serum GAA in acute pancreatitis rats. GAA may be synthesized in the acinar pancreas, and insulin can directly regulate the function of acinar pancreas including GAA synthesis.

Acute Disease↗
PubMed1989

[Analysis of ocular circulatory kinetics in glaucoma by the ultrasonic Doppler method].

In order to analyze ocular circulatory kinetics in relation to the stages of progression of primary open-angle glaucoma, the pulse wave of flow velocity in the central retinal artery was measured by the ultrasonic Doppler method. In eyes with glaucoma, the ratio of blood flow velocity of the central retinal artery (fundus artery: FA) to that of the ophthalmic artery (medial frontal artery: OA) was smaller and, at the same time, the pulse rise time (PRT) of the pulse wave of flow velocity was shorter than in normal eyes, a tendency which increased as the disease progressed. The ratio of FA to OA in terms of velocity [V (FA/OA)] showed a significant inverse correlation with the degree of visual field disorder (Kosaki classification) and the ratio in terms of PRT [T (FA/OA)] showed significant inverse correlation with the C/D ratio of the papilla. An ultrasonic Doppler blood flowmeter with 2 frequencies, attached to an integral spectrum analyzer for indicating the direction of blood flow using real time sonography (Vasoflo-3), was used. The investigation was conducted on 100 eyes with primary open-angle glaucoma in 60 patients aged 20-70 years [28 males and 32 females (mean age 64.3 +/- 12.1)], and 60 eyes in 30 normal subjects of the same age (mean age 58.1 +/- 14.3). These results demonstrated that the ultrasonic Doppler method is useful for the observation of ocular circulatory kinetics in eyes with glaucoma.

Adult↗
PubMed1989

[Loco-regional cancer chemotherapy with a new drug delivery system, "anticancer drug-fibrin clot"].

Five different types of anticancer drugs were individually entrapped into fibrin clots using our own material, "G.T.XIII" to provide an "anticancer drug-fibrin clot" for regional cancer chemotherapy. Anticancer drugs used in the present study were ADM, MMC, MTX, 5-FU and cDDP. The release of drugs from fibrin clots was studied in vitro. Each fibrin clot was intraperitoneally administered to cancer (AH-130)-bearing rats to evaluate the oncolytic effects. The activities of anticancer drugs delivered from the clots were maintained for more than two weeks. Survival terms of cancer bearing rats were remarkably prolonged with the anticancer drug-fibrin clots. Neither recurrence of ascites nor metastases of malignant cells was observed in the rats treated with such clots. Our newly devised anticancer drug-fibrin clots showed a sustained release of oncolytic drugs and favorable antineoplastic effects. This newly devised drug delivery system suggested a clinical potential for regional cancer chemotherapy.

Animals↗
PubMed1988

Possible binding sites for inositol 1,4,5-trisphosphate in macrophages.

We reported that an arylazide derivative of inositol 1,4,5-trisphosphate (InsP3) caused irreversible InsP3-induced Ca2+ release from saponin-permeabilized macrophages after photoirradiation. To determine the specific receptors for InsP3, presumably present on the endoplastic reticulum, we synthesized isotope-labeled arylazide derivatives of InsP3; InsP3 was coupled with p-azidobenzoyl [3H]beta-alanine (InsP3-[3H]AB beta A) or p-[125I]azidosalicyl beta-alanine (InsP3-[125I]AS beta A). We report here that three proteins may be associated with the Ca2+ releasing mechanism, in photoirradiated saponin-permeabilized macrophages and in the microsomal fraction.

Animals↗
PubMed1988

Cellular glutathione conjugation of aziridines in isolated rat hepatocytes.

Glutathione conjugation of aziridines was found in isolated rat hepatocytes in experiments using the optical isomers of (1- and d-) aziridinecarboxylic acid (AZC) and (1- and d-) 1-methyl-2-beta-naphthylaziridine (NAZ). 1-AZC much more effectively consumed glutathione than d-AZC, and the yield of the glutathione conjugate during 2 hr of incubation exceeded 200% of the cellular glutathione detected at the initiation of the incubation. Such a high yield of 1-AZC-GSH conjugate would occur only when conjugation efficiently proceeds without interference against the GSH resynthesis route in the liver cells. The cytotoxicity of 1-AZC was very weak and did not affect cell viability of the isolated hepatocytes even after the formation of AZC-GSH conjugate. Consequently, we supposed that GSH is not essential for supporting the viability of the isolated hepatocytes. For very slow GSH conjugate formation of d-AZC, we envisaged poor membrane transport of the d-isomer resembling to the selective incorporation of d- and 1-proline observed in some plant cells. Both isomers of NAZ were markedly cytotoxic and depressed the cell viability. The yield of the glutathione conjugate from NAZ did not exceed the cellular GSH level detected at the initial stage of incubation. The highly cytotoxic compound nitrosomethane, generated in the first biotransformation step of the metabolism of NAZ, can obstruct the resynthesis route of GSH by inhibiting the ATP generation process as discussed previously (Ref. 3). Decreasing the cellular GSH by treatment with 1-AZC enhanced the susceptibility of the isolated hepatocytes to NAZ toxicity. d-AZC did not affect the viability of cells treated with NAZ.

Animals↗
PubMed1988

Purification and characterization of inositol 1,4,5-trisphosphate 3-kinase from pig aortic smooth muscle.

Inositol 1,4,5-trisphosphate (InsP3) 3-kinase, which phosphorylates InsP3 to form inositol 1,3,4,5-tetrakisphosphate, was purified to apparent homogeneity by (NH4)2SO4 fractionation and sequential chromatographic steps on DEAE-sepharose, calmodulin-Affi-Gel and DEAE-5PW h.p.l.c. The purified enzyme had a specific activity of 24.4 nmol of inositol tetrakisphosphate formed/min per mg of protein, which represented a purification of approx. 195-fold with a 0.29% recovery, compared with the cytosol fraction of the muscle. SDS/polyacrylamide-gel electrophoresis showed a single protein-staining band of Mr 93,000. Moreover, the major protein peak, of Mr 84,000, was detected by TSK gel G3000SW gel-permeation chromatography of the purified sample. As this value was approximately consistent with the Mr determined by SDS/polyacrylamide-gel-electrophoretic analysis, the InsP3 3-kinase might be a monomeric enzyme. The purified enzyme had a Km for InsP3 of 0.4 microM, with an optimum pH range of 5.8-7.7. The enzyme was maximally activated by calmodulin, with a stoichiometry of 1:1.

Animals↗
PubMed1988

Effects of human recombinant tumor necrosis factor-alpha and interleukin 1 on the synthesis of glycosaminoglycan and DNA in cultured rat costal chondrocytes.

We examined effects of human rTNF alpha on the synthesis of glycosaminoglycan and DNA in cultured rat costal chondrocytes. The effects of human recombinant IL-1 alpha and IL-1 beta were also given attention. rTNF alpha, as well as rIL-1 alpha and rIL-1 beta, decreased the incorporation of [35S]sulfate into glycosaminoglycan to about 10% of the levels in the control. The half-maximal doses of rTNF alpha, rIL-1 alpha or rIL-1 beta required for the suppression of glycosaminoglycan synthesis (by rTNF alpha, rIL-1 alpha, and rIL-1 beta) were 2 ng/ml, 30 ng/ml, or 5 ng/ml, respectively. rTNF alpha stimulated incorporation of [3H]thymidine in the chondrocytes in a dose- and time-dependent manner. DNA synthesis was increased to about threefold over the control cultures in the presence of 1 microgram/ml rTNF alpha for 72 hr. The stimulatory effect of rTNF alpha on DNA synthesis was observed in both subconfluent and confluent cultures, whereas rIL-1 alpha and rIL-1 beta had no stimulatory activity on DNA synthesis. The addition of rTNF alpha to the cultures of chondrocytes stimulated DNA synthesis, even in medium containing no fetal calf serum. The fetal calf serum acted synergistically with rTNF alpha in increasing DNA synthesis. We propose that both TNF and IL-1 may be involved in inflammatory diseases of cartilage, and that TNF alpha, but not IL-1, may have some physiologic growth factor function for chondrocytes.

Animals↗
PubMed1988

Possible physiological role of guanosine triphosphate and inositol 1,4,5-trisphosphate in Ca2+ release in macrophages stimulated with chemotactic peptide.

The release of Ca2+ induced by inositol 1,4,5-trisphosphate (InsP3) in the presence of GTP was examined by using saponin-permeabilized macrophages. The origin and the amount of mobilized Ca2+ in intact macrophages stimulated with chemotactic peptide were also examined to assess the physiological significance of GTP and InsP3 on Ca2+-releasing activities. The total amount of Ca2+ released by 20 microM-A23187 from the unstimulated intact macrophages was 1.4 nmol/4 x 10(6) cells, and the mitochondrial uncoupler did not cause an efflux of Ca2+ from the cells. The Ca2+ accumulation by the non-mitochondrial pool(s) was inhibited by the presence of GTP, and the total amount of releasable Ca2+ (1.4 nmol/4 x 10(6) cells) was comparable with that accumulated by the non-mitochondrial pool(s) in the presence of GTP at a free Ca2+ concentration of 0.14 microM. The mobilized and subsequently effluxed Ca2+ in cells stimulated with chemotactic peptide was estimated to be 0.3 nmol/4 x 10(6) cells. Much the same amounts were released by about the half-maximal dose of InsP3 from the non-mitochondrial pool(s) of saponin-treated macrophages that had accumulated Ca2+ at a free concentration of 0.14 microM in the presence of GTP. These results suggest that the Ca2+-releasing activity induced by GTP may play a role in the long-term regulation of Ca2+ content in the non-mitochondrial pool(s) of macrophages, and that released by InsP3 can explain, quantitatively, the chemotactic-peptide-induced mobilization of Ca2+.

Animals↗