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Biomedical subjects

K Morimoto

Publications and source records attributed to K Morimoto.

At least 487 records · Page 27Linked to original sources
PubMed1990

[Genotoxicity of synthetic dyes in the umu test using Salmonella typhimurium TA1535/pSK1002 (II). Results of examination of basic dyes].

In the present study, SOS-inducing activity of 76 basic dyes was investigated by umu test using Salmonella typhimurium TA1535/pSK1002 under the condition of absence and presence of rat liver microsomal fraction. The test was carried out with five doses of basic dyes (400, 120, 40, 12, and 4 micrograms/ml). The samples showing beta-galactosidase activity more than 1.5-fold over the background level were reexamined and the dose-response curves were prepared at various doses. Thereafter, samples showing beta-galactosidase activity unit more than 1.5-fold of the background level were defined as genotoxic. Among the basic dyes examined, 13 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Blue 40, Blue 47, Brown 14, Orange 30, Red 24, Violet 30, Violet 31, Yellow 13(h), Yellow 19, Yellow 25, Yellow 67, and Yellow 73 and in the presence of S9, Orange 47 was judged as genotoxic in addition to the aforementioned dyes. An evident dose-response relationship between the doses of the dye and umu gene expression was observed in these 13 dyes.

Coloring Agents↗
PubMed1990

[Beneficial effect of a selective TXA2 synthetase inhibitor, OKY-046, both on thromboxane B2 production and vascular damage after spinal cord injury in rat spinal cord].

Thromboxane A2 (TXA2) is an eicosanoid with potent platelet aggregation and vasoconstricting activity, while prostaglandin I2 (PGI2) antagonizes its activity. But these eicosanoids are so labile that the stable degradation products, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), are determined in biological materials. In a rat spinal cord compression injury model, a production of TXB2 reached a peak (133.6 +/- 13.8 pmol/g cord) 5 minutes after compression injury, while that of 6-keto-PGF1 alpha slightly increased (26.2 +/- 11.7 pmol/g cord). And the magnitude of the increase in TXB2 and the extent of post-traumatic vascular damage as determined by fluorescein uptake were both dependent on the degree of spinal cord compression injury. We also studied the effect of a selective TXA2 synthetase inhibitor, OKY-046 [E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid), both on TXB2 production in the injured spinal cord and post-traumatic vascular damage. When OKY-046 was administered intravenously 10 minutes prior to compression injury at a dose of 500 micrograms/kg body weight, the increased production of TXB2 was inhibited by about 80% and uptake of sodium fluorescein was reduced by a maximum of 40%. When the compression injury was induced before OKY-046 was administered, the inhibitory effect of OKY-046 on TXB2 production decreased depending on the duration before administration. In contrast, the 6-keto-PGF1 alpha level was not affected in the presence of OKY-046.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effects of the kallikrein-kinin system on phasic coronary vasospasm in dogs.

It is well known that kinins are liberated from kininogen in blood during angina attack to maintain blood flow in coronary artery. We examined the effects of bradykinin, one of kinins, on the coronary artery other than vasodilation. The isolated canine coronary artery ring was suspended in gassed (95% O2, 5% CO2) Krebs-Henseleit buffer at 37 degrees C in vitro. The experimental phasic contraction of coronary artery was induced by 6 x 10(-4)M of 3,4-diaminopyridine which decreases K conductance (Y. Uchida, Jpn. Circ. J: 49, 128, 1985). The effect of bradykinin and other substances on the cycle length of contraction (CL), the peak tension of contraction phase (PT) and the tension during relaxation phase (RT) were observed. The phasic contraction was eliminated by 10(-7)M nifedipine and 10(-6)M diltiazem which block voltage dependent Ca channels. These Ca blockers reduced PT, but slightly increased CL, and weakly reduced RT. The phasic contraction was also eliminated by 10(-6)M bradykinin. However, bradykinin, unlike Ca blockers, did not reduce PT, but markedly prolonged CL and decreased RT significantly. This inhibition mode was very similar to those of nicorandil which increases K conductance. These data suggest that bradykinin plays a protective role in coronary vasospasm, and this antivasospasm effect may be mediated through the increase in K conductance.

Animals↗
PubMed1989

A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead.

A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALA-U-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 +/- 22 micrograms/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-U-CL level (0.83 +/- 0.14 and 2.4 +/- 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 +/- 22 micrograms/l Pb-B (P less than 0.05, n = 26), while that of ALA-U-CL was observed at 245 +/- 30 micrograms/l Pb-B (P less than 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 micrograms/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALA-U-CL above the cut-off point (3.5 mg/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗
PubMed1989

Effect of a noncompetitive antagonist (MK-801) of NMDA receptors on convulsions and brain amino acid level in E1 mice.

Anticonvulsant action of MK-801, a novel noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor, was examined in genetically epileptic E1 mice. Systemic injection of MK-801 (0.1-1.0 mg/kg) potently suppressed generalized tonic-clonic convulsions of in a dose-dependent manner (ED50, 0.17 mg/kg). This anticonvulsant effect of MK-801 appeared at a dose which did not induce any obvious behavioral changes. Following the administration of a fully anticonvulsant dose of MK-801 (1 mg/kg), amino acid analysis revealed a significantly elevated level of glycine in the hippocampus. Levels of other amino acids including glutamate, aspartate, taurine, glutamine, alanine, and gamma-aminobutyrate were not changed either in the hippocampus or in the cerebral cortex. This study suggests that NMDA system may play an essential role in seizure-triggering mechanisms in E1 mouse.

Amino Acids↗
PubMed1989

Modification of amygdala kindling by intracerebroventricularly administered gangliosides in rats.

The present study evaluated the effects of intracerebroventricularly (icv) administered total brain gangliosides on amygdala (AM) kindling in rats. The results showed the following: (i) exogenously injected gangliosides (0.4 and 0.8 mg/4 microliter) significantly decreased the afterdischarge threshold (ADT) in a dose-dependent manner; (ii) both 0.8 and 0.25 mg gangliosides significantly facilitated AM-kindled seizure development and shortened total AD duration when AM stimulation was given at 2-h intervals, especially in the late stages of kindling (stages 3-5); (iii) the facilitated kindled epileptogenesis by gangliosides was maintained persistently for more than 2 weeks; (iv) 0.25 mg gangliosides did not affect previously kindled seizures; (v) 0.8 mg gangliosides had a proconvulsant action in both nonkindled and kindled rats; and (vi) epileptiform responses to gangliosides markedly increased during kindling and remained increased for at least 5 weeks after kindling. It is concluded that gangliosides in neuronal membranes in the CNS may play an important role in the permanent hyperexcitability of kindled epileptogenesis.

Amygdala↗
PubMed1989

Structure and transcription of the glycoprotein gene of attenuated HEP-Flury strain of rabies virus.

The mRNA-encoding G protein of the attenuated HEP-Flury strain of rabies virus was sequenced by the cDNA cloning technique. The G-mRNA was composed of 2059 nucleotides, with the coding region located from the 28th to 1602nd nucleotide, and was capable of encoding a polypeptide of 524 amino acids. Although the coding region was highly homologous (90% or more) to that of ERA and PV strains, the 3' noncoding region of the HEP virus G-mRNA was longer than that reported for other strains by some 400 nucleotides. The extra sequence was homologous to the long G-L intergenic sequence of the PV viral genome. The HEP virus genome lacked the postulated polyadenylating signal (TG-AAAAAAAA) that should have been found just before the "long G-L intergenic region," which indicates that the long G-L intergenic region of the HEP virus is integrated into the preceding G gene, and is transcribed only as a portion of the G-mRNA molecule. In the ERA virus-infected cells, however, two species of G-mRNA (1.9 and 2.3 kb long) were produced. The longer G-mRNA also contained the sequence complementary to the long G-L intergenic region and the shorter one did not. These findings suggest that two different poly(A)-tailing signals (one is present just before and another at the end of the long G-L intergenic region) work toward terminating the transcription of the ERA virus G gene and that the longer G-mRNA is produced as a readthrough product.

Amino Acid Sequence↗
PubMed1989

Evaluation of polyvinyl alcohol hydrogel as a sustained-release vehicle for rectal administration of indomethacin.

In order to evaluate an indomethacin polyvinyl alcohol (PVA) hydrogel for rectal administration, the in vitro release characteristics of indomethacin from the hydrogel and indomethacin plasma concentrations after rectal administration were examined. The PVA hydrogel containing indomethacin was prepared by a low-temperature crystallization method. The release of indomethacin from the PVA hydrogel agreed with the Fickian diffusion model for 10 hr. Rectal administration of indomethacin hydrogels to rats yielded high indomethacin plasma concentrations, without producing a sharp peak, and a sustained-release effect. In dogs, the indomethacin hydrogel produced a similar sustained-release effect; however, the indomethacin plasma concentration was relatively low compared with that of an indomethacin suppository.

Administration, Rectal↗
PubMed1989

Correlation between the DNA damage in urinary bladder epithelium and the urinary 2-phenyl-1,4-benzoquinone levels from F344 rats fed sodium o-phenylphenate in the diet.

The relationship between urinary metabolites and DNA damage in the urinary bladder epithelium of male and female rats was tested by alkaline elution assay after an intravesical injection of OPP or its urinary metabolites. 2-Phenyl-1,4-benzoquinone (PBQ) revealed a weak DNA-damaging activity in both sexes at 0.05-0.1%. OPP and phenylhydroquinone (PHQ) had no effects at the same level. Histopathologically, a single intravesical injection of 0.1% PBQ induced epithelial hyperplasia of the bladder epithelium on day 5, but PHQ and OPP did not induce it. Feeding studies with OPP-Na were also performed to examine the correlation between urinary PBQ levels and DNA damage in bladder epithelium. Slight DNA damage was observed in males given 1.0 and 2.0% OPP-Na in the diet for 3-5 months. The damage was dependent upon the dietary levels of OPP-Na. The amounts of OPP, PHQ and PBQ in urine were well correlated with the dietary levels of OPP-Na for male rats. The amounts of OPP, PHQ and PBQ were greater in male rats than in females given 2.0% OPP-Na diet for 5 months. The urinary pH of males was slightly higher than that of females. Since 0.4% sodium bicarbonate did not cause DNA damage in the in-situ study, the urinary alkalinity may not affect the initiation steps of urinary carcinogenesis by OPP-Na. The present results indicate that the metabolite PBQ is the reactive species for the initiation steps of bladder tumors induced by OPP-Na and OPP.

Animals↗
PubMed1989

Clinical considerations and biochemical basis of prognosis of cervical spinal cord injury.

A total of 118 patients with cervical spinal cord injury were studied to determine the neurologic improvement achieved by either conservative or surgical treatment. Useful recovery was observed in 55% of the patients with incomplete cord injuries, but in none of those with complete cord injuries. There was no significant difference between the treatment groups regarding neurologic improvement. In experimental studies on rats, the increased levels of lipid peroxides and thromboxane after spinal cord injury were found to be proportional to the magnitude of injury. These evidences suggest that spinal cord injury is directly related with the magnitude of injury, and the prognosis is determined entirely at the time of injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

In situ freezing of the rat urinary bladder: DNA adduct formation in the bladder epithelium demonstrated by 32P-postlabeling assay.

In situ freezing of the urinary bladder has been demonstrated to exert tumor-initiating potential in two-stage urinary bladder carcinogenesis in the rat. In the present experiment, DNA modification was examined after in situ freezing of the whole urinary bladder performed by pinching with frozen forceps at -15 degrees C or -30 degrees C for 2 s. The 32P-postlabeling analysis revealed at least 2 DNA adducts in the epithelial cells of the urinary bladder collected 3 days after freezing. Single-strand breaks of DNA were also found by means of the alkaline elution assay in the bladder epithelium collected 10 min after freezing. Thus, the previously demonstrated tumor-initiating activity of in situ freezing in urinary bladder carcinogenesis was revealed to be associated with substantial DNA damage and adduct formation.

Animals↗
PubMed1989

Design of polyvinyl alcohol hydrogel as a controlled-release vehicle for rectal administration of dl-propranolol-HCl and atenolol.

Preparations of beta-blockers, propranolol-HCl and atenolol, in poly(vinyl alcohol) (PVA) hydrogel were designed for the therapeutic treatment of hypertension by transrectal delivery. In vitro release characteristics and plasma drug concentration profiles after rectal administration in rats and dogs were examined. The PVA hydrogels containing beta-blockers were prepared by a low-temperature crystallization method. The release of beta-blockers from hydrogel preparations was consistent with Fickian diffusion (Higuchi model); the drug release versus the square root of release time profile gave a straight line over 60% of the total release process. The release of beta-blockers from hydrogel preparations increased at higher concentrations of PVA in the hydrogel preparations and was not affected by the pH of hydrogel preparations. Plasma concentrations of beta-blockers after rectal administration of hydrogels were higher than those after administration of suppositories (Witepsol H-15) in rats and dogs. The drug plasma concentrations increased at higher concentrations of PVA in hydrogel preparations. In the case of propranolol, which is a hepatic high-clearance drug, area under the blood concentration curve, 0-8 h after rectal administration of a hydrogel preparation (20% w/w PVA, pH 7.0) was 2.16 times and 5.26 times higher than those obtained with Witepsol H-15 suppository and oral administration, respectively. Rectal administration with PVA hydrogels is a favorable route for a hepatic high-clearance drug such as propranolol.

Animals↗
PubMed1989

Echocardiographic assessment of aneurysm of the aortic valve caused by infective endocarditis--a case report.

No aneurysm of the aortic valve associated with infective endocarditis has yet been reported. This report describes the clinical echocardiographic and pathologic findings in a patient who developed infective endocarditis resulting in aneurysm of the non-coronary cusp with aortic regurgitation. Surgical treatment was performed because of gradual expansion of the aneurysm and gradual thinning of its wall. Two-dimensional and color Doppler echocardiographies proved useful for the initial diagnosis and serial follow-up of this unusual case and for its successful surgical management.

Aortic Valve↗
PubMed1989

[The anti-mutagenic effects of human saliva investigated by umu-test. Part 1. Effects of filtration and storage at low temperatures].

The anti-mutagenic effects of human saliva were examined by the umu-test. The SOS-inducible DNA-damaging activity of AF-2 was markedly decreased by pre-treatment with human fresh saliva. The anti-mutagenic activity of human saliva was retained even after the filtration (0.45 microns). This activity was also observed after 24 hr-storage at 10 degrees C or -12 degrees C. These results were consistent with previous reports using Ames tests. Significant differences in the activity, however, were observed between sample donors and between experiments with the same sample donor. Further analyses of the effects of the factors contained in saliva as well as the effects of life-styles, including dietary-habits of sample donors will be necessary.

Adult↗
PubMed1989

Occupational asthma from cobalt sensitivity in workers exposed to hard metal dust.

Eight asthmatic patients who had no history of asthma before starting work in a hard-metal plant and eight control subjects (three atopic, three nonatopic asthmatic, and two normal volunteers) without a history of exposure to hard metal dust were subjected to provocation tests, skin tests, radioallergosorbent tests (RAST) and Farr test with cobalt. Four of the eight patients were atopic, and seven showed bronchial hyperresponsiveness to methacholine (BHR). Patch and intradermal skin tests with cobalt chloride (CoCl2) could not discriminate the patients from control subjects. All patients had positive reactions to CoCl2 in the provocation tests; two developed immediate asthmatic reaction (IAR), four late asthmatic reaction (LAR), and two dual asthmatic reaction (DAR), while the control subjects showed no reaction. Evidence of specific IgE antibodies to cobalt-conjugated human serum albumin (Co-HSA) was presented by four patients (RAST score greater than 2) based on comparison of serum samples from 60 asthmatic patients and 25 asymptomatic workers in the same plant. Positive serum samples selectively bound 57Co, and the test was blocked by nonlabled cobalt sulfate (CoSO4). These findings suggest the development of hard metal-induced asthma from cobalt sensitivity.

Adult↗
PubMed1989

[Evaluation of the self-administered respiratory questionnaire recommended by the Japanese Labour Ministry based on the standardized interviewer-administered BMRC questionnaire].

The self-administered respiratory questionnaire on persistent cough or sputum prepared and recommended by the Japanese Labour Ministry to detect pneumoconiosis was evaluated and compared with the Japanese version of the standardized interviewer-administered respiratory questionnaire developed by the British Medical Research Council (BMRC). The two questionnaires were given to 800 subjects on the same day. Because the wording of the questions was similar, the two questionnaires yielded very similar results. In terms of the overall prevalence of persistent cough or sputum, no important differences could be demonstrated between the results of the two questionnaires. The results of this study indicate that the self-administered questionnaire has good concordance with the BMRC questionnaire. When compared to the BMRC questionnaire, the specificity of the self-administered questionnaire was found to be more than 99%, but the sensitivity was inferior to the specificity, being less than 80%. When confined to subjects with persistent cough or sputum for two years or more, the sensitivity was up to 84%. These findings suggest the responses of the subjects to the self-administered questionnaire tend to be negative. A validity of the self-administered questionnaire needs to be further studied among dust workers including pneumoconiotics.

Adult↗