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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 721 records · Page 40Linked to original sources
PubMed1983

Impairment of thermoregulatory cooling behavior by single cortical spreading depression in the rat.

Effects of single waves of unilateral cortical spreading depression (CSD) on skin-cooling operant behavior were studied in the rat with and without unilateral lesion in the preoptic and anterior hypothalamus (PO/AH). The skin-cooling behavior was severely suppressed for 6 min, with a resulting rise in rectal temperature (Tre), when CSD entered the frontal cortex contralateral to the PO/AH lesion. However, CSD ipsilateral to the PO/AH lesion slightly suppressed the skin-cooling behavior for 4 min with small rise in Tre. In the PO/AH intact rat, while 0.9% NaCl did not affect the skin-cooling behavior, unilateral CSD slightly suppressed it for 3 min almost in the same way as that of the ipsilateral CSD trial in the PO/AH lesioned rat. The results add further evidence to support the involvement of the frontal cortex in the central control of thermoregulation.

Animals↗
PubMed1983

Long-term toxicity and carcinogenicity test of ammonia-process caramel colouring given to B6C3F1 mice in the drinking-water.

Caramel colouring (ammonia process) was given at levels of 0 (control), 1.25 and 5.0% in the drinking-water to groups of 50 male and 50 female mice for 96 wk, and then all all the animals were maintained without caramel for a further 8 wk. Males given 5.0% caramel showed increased cumulative mortality from wk 100 to the end of the experiment. The white blood cell count in treated males was significantly elevated in a dose-related manner. However, these changes were not considered to be biologically significant. There were no treatment-related effects on clinical signs, body or organ weights, results of urine analyses, or histological features. Therefore, this study did not demonstrate any carcinogenic effect of caramel on mice at levels of up to 5.0% in the drinking-water.

Ammonia↗
PubMed1983

Promoting effects of various chemicals in rat urinary bladder carcinogenesis initiated by N-nitroso-n-butyl-(4-hydroxybutyl)amine.

We studied the capacity of various chemicals to promote urinary bladder cancer in male F344 rats after initiation by N-nitroso-n-butyl-(4-hydroxybutyl)amine (BBN). The rats were given initially 0.01% BBN in the drinking-water for 4 wk and then the test compound in the diet for 34 wk. Effects were judged by measuring the formation of preneoplastic lesions papillary or nodular hyperplasia (PN hyperplasia) of the urinary bladder. Administration of 5%, but not 0.5% (w/w) sodium saccharin in the diet significantly increased the incidence and extent of PN hyperplasia. This finding could be related to the induction of cancers in the rat urinary bladder by high levels of saccharin. Sodium ascorbate (5%). DL-tryptophan (5%) and allopurinol (0.02%) also significantly increased the extent of PN hyperplasia in the affected animals, but other test chemicals, such as acetazolamide (0.35%) and quercetin (5%) did not. The results with sodium saccharin and DL-tryptophan were consistent with previous findings and suggest that sodium ascorbate and allopurinol have promoting activities in urinary bladder carcinogenesis in rats. No correlation was found between the extent of crystalluria and promotion of preneoplastic lesions.

Acetazolamide↗
PubMed1983

Molecular modelling of protein-nucleic acid interactions.

Computer modeling techniques to study the interaction of proteins with nucleic acids are presented. The methods utilize information from genetic and chemical modification experiments and macromolecular structural constraints. These techniques, in addition to computer model building procedures and theoretical energy calculations, are illustrated for the study of the lac and cro repressor-operator systems. Our predicted interactions between lac and its operator agree with those recently reported for lac based upon sequence alignment with the cro repressor. Several molecular models of the putative helical segment of cro interacting with its OR3 operator are presented. These models are reflective of intermediate conformations experienced by the repressor in recognition of the operator sequence. The results of our studies are further discussed in terms of the design of short peptides interacting with nucleic acid sequences and the evolutionary requirements in establishing these repressor interactions.

Amino Acid Sequence↗
PubMed1983

Animal pharmacokinetics and toxicology of cefotetan--a new cephamycin antibiotic.

In animal pharmacokinetic studies the biological half-lives of cefotetan were 13.0 min in mice, 15.9 min in rats, 30.5 min in rabbits, 55.5 min in dogs and 77.9 min in rhesus monkeys. The acute intravenous LD50 values (g/kg) were 6.4 and 5.0 in male and female mice, respectively, and 8.5 and 6.8 in male and female rats, respectively. Six-month repeated dose studies of 30 to 1000 mg/kg per day intraperitoneally in rats and 100 to 600 mg/kg per day intravenously in rhesus monkeys showed no notable organ toxicity. A teratogenicity study in rats indicated that cefotetan had no adverse effects on fetal and postnatal development. The nephrotoxicity of cefotetan in rabbits was considerably less than that of cefazolin.

Abnormalities, Drug-Induced↗
PubMed1983

Mechanism of uncoating of influenza B virus in MDCK cells: action of chloroquine.

Exposure of influenza B virus-infected MDCK cells to chloroquine at the time of infection resulted in significant inhibition of infection. The appearance of input virus in the intracellular vesicles was not affected in the presence of the drug, but primary transcription of the virus genome did not occur. Chloroquine caused a rapid rise in the pH inside the lysosomes of MDCK cells, to 6.5 from the physiological pH 5.6. In contrast, exposure of infected cells incubated in acidic medium (pH 6.0) to chloroquine did not cause an increase in lysosomal pH and this low pH treatment during the chloroquine-sensitive phase was followed by virus production. Influenza B virus induced haemolysis of chick erythrocytes at low pH values (5.0 to 5.9) which was associated with cell-cell membrane fusion. It is likely that chloroquine prevents the uncoating of influenza B virus by increasing the lysosomal pH above the critical value required for inducing fusion between the virus envelope and the lysosomal membrane.

Animals↗
PubMed1983

Effect of high salt treatment on influenza B viral protein synthesis in MDCK cells.

Based on the information that high salt inhibits the initiation of cellular mRNA translation which depends on the function of the 5'-terminal structure of mRNA, we compared the effect of high salt on translation of host cellular mRNAs and influenza viral mRNAs, both of which are of 5'-terminal structure. Brief exposure of influenza B virus-infected MDCK cells to high salt medium resulted in a dose-dependent inhibition of viral polypeptide synthesis as well as of cellular polypeptide synthesis, but it had less effect on synthesis of viral polypeptides, particularly nonstructural protein (NS). Under these conditions the Na+ content of the infected cells was significantly increased. A similar salt effect on in vitro translation of viral and cellular mRNAs extracted from infected cells was also observed. There was no significant difference in sensitivity to hypertonic block of in vivo translation of influenza viral mRNAs and vesicular stomatitis virus mRNAs, the latter of which possess a virus-directed structure at the 5'-terminus.

Animals↗
PubMed1983

Augmentation of bethanechol-stimulated gastric secretion by lowering body temperature in water-immersed rats.

The present study was designed to elucidate influences of hypothermia on gastric secretory response to secretagogues (bethanechol, histamine and tetragastrin) in rats exposed to restraint plus water immersion (36 and 25 degrees C) stress. In vagotomized rats provided with a pH microelectrode, decrease in intragastric pH by bethanechol (75 micrograms/kg, i.p.) was markedly produced under the water-immersion at 25 degrees C and the extent of the pH decrease was significantly greater than that observed under the water-immersion at 36 degrees C. However, intragastric pH decrease by histamine (1 mg/kg, i.v.) or tetragastrin (60 micrograms/kg/20 min, i.v.) was not affected by varying water temperatures. Using a technique of pyloric ligation, gastric acid and pepsin responses to bethanechol were measured at doses of 50-100 micrograms/kg in vagotomized rats and also at doses of 0.5-1.0 mg/kg in vagally intact rats. Stimulation of acid and pepsin secretion by bethanechol was provoked only under the water-immersion at 25 degrees C. As compared with the values obtained under the water-immersion at 36 degrees C, a significant augmentation of bethanechol-stimulated secretion was seen for acid and pepsin output in vagotomized rats and seen for acid output in vagally intact rats under the water-immersion at 25 degrees C. These results suggest that hypothermia may operate some mechanism for increasing the secretory responsiveness of the stomach to cholinomimetics.

Animals↗
PubMed1983

Clinical study of complications in dialyzed diabetics.

The authors retrospectively investigated 62 diabetics who had received dialytic therapy at our department and our associated hospital over the past 10 years. We studied the complications and causes of death among the 62 subjects. Of the 62 patients (male 42, female 20), 27 (male 21, female 6), had died. The causes of death in the 27 cases included 7 from general weakness, 4 from gastrointestinal bleeding, 4 from cerebrovascular hemorrhage or thrombosis, 3 suicide, 3 congestive heart failure, 2 myocardial infarction, 2 hyperkalemia, 1 infection and 1 from hepatoma. With regard to diabetic retinopathy, 19 of the 62 patients suffered from bilateral blindness and 12 from unilateral blindness. In 8 patients, visual complications developed after hemodialysis, but 16 patients were already blind at the introduction of hemodialysis. There was no evidence that retinopathy was accelerated by dialysis and the authors suggest that the treatment of retinopathy is very important at the nondialyzed stage. With regard to other complications in dialyzed diabetics, unstable hypertension, diabetic gastroenteropathy, peripheral neuropathy, ischemic heart disease and gangrene were discovered in our population. Some rehabilitation was possible in all but 3 of the subjects (1 peripheral neuropathy, 2 leg amputation).

Adult↗
PubMed1983

Syntheses of deuterated phenylpropionic acid derivatives.

2-(4-(2-Thienylhydroxymethyl)phenyl) propionic acid (I), 2-(4-carboxyphenyl) propionic acid (II), 2-(4-(5-hydroxy-2-thienylcarbonyl)phenyl)propionic acid (III) were labeled with multiple-deuterium for the purpose of using as internal standards in studies on the metabolism of 2-(4-(2-thienylcarbonyl)phenyl)propionic acid (suprofen, IV), anti-inflammatory agent, in man and animals by the mass fragmentography. I-d4 was obtained in a 93% yield from IV-d4 by reduction with sodium borohydride, and its deuterium content was 99 atom%. On the other hand, II-d4 (99 atom% D) was obtained by four-step synthesis from 2-((4-bromophenyl-d4)1, 1-ethyleneglycol)propane (V) in a 43% yield and III-d4 (98.4 atom% D) by five-step synthesis from V in a 12% yield.

Anti-Inflammatory Agents↗
PubMed1983

Microbial transformation of maridomycin III by Serratia marcescens.

Two transformation products of maridomycin (MDM) III, MDM-S1 and MDM-S2 named after Serratia marcescens, were isolated by silica gel chromatography. NMR and IR analysis revealed that MDM-S1 and -S2 had no aldehyde group at C-18 on the macrolactone ring, and that the hydroxyl group at C-9 seemed to disappear. Although MDM-S1 and -S2 are less active against Gram-positive bacteria than starting MDM III they are interesting materials in view of the introduction of nitrogen into each molecule, and that the transformation products are produced by Gram-negative bacteria which are thought to be insensitive to macrolide antibiotics.

Bacteria↗
PubMed1983

Carcinogenicity of butylated hydroxyanisole in F344 rats.

Butylated hydroxyanisole (BHA) was added at levels of 0.5 and 2.0% to the diet of inbred F344 rats for 2 years. The higher dose of BHA induced a significant increase in the incidence of papilloma and squamous cell carcinoma in both sexes. Both the higher and lower doses increased the incidences of hyperplasia of the forestomach, considered to be associated with neoplasias. The incidences of these neoplastic changes were dose-dependent. Neoplastic changes in other organs were not increased significantly by BHA. These results show that BHA is carcinogenic in the forestomach of F344 rats.

Animals↗
PubMed1983

Carcinogenicity of dipyrone in (C57BL/6 X C3H)F1 mice.

The carcinogenicity of dipyrone (sulpyrin)--[(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4 -yl) methylamino]methanesulfonic acid sodium salt monohydrate--which is widely used as an antipyretic anodyne in Japan and in some European countries, was examined in 314 (C57BL/6 X C3H)F1 mice. Male animals were given 0.5% (group I-a) or 0.125% (group I-b) dipyrone in their drinking water for 78 weeks, and female animals were given 1.0% (group II-a) or 0.25% (group II-b) dipyrone in their drinking water for 78 weeks; both males and females were observed for 86 weeks. Twenty-seven of 48 (56%) group I-a animals and 36 of 44 (82%) group II-a animals developed hepatic tumors, and the tumors in group II-a mice developed earlier than those in the control animals. The tumor incidences were significantly higher than those of 8 of 44 (18%) and 3 of 51 (6%) in the respective control groups. The multiplicity of the hepatic tumors was also significantly increased in groups I-a, I-b, and II-a. Hepatic adenoma incidence was related to the dose of dipyrone in the males. These results show that dipyrone enhances the development of hepatic tumors in mice.

Aminopyrine↗