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Biomedical subjects

T Murai

Publications and source records attributed to T Murai.

At least 91 records · Page 5Linked to original sources

Infrequent involvement of microsatellite instability in urinary bladder carcinomas of the NON/Shi mouse treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

Variation in the frequency of microsatellite instability (MSI) has been reported in different kinds of human malignant tumors, with less than one-third of invasive urinary bladder carcinoma cases estimated to be affected. Here we investigated the MSI for 27 microsatellite sequences in invasive urinary bladder carcinomas of the NON/Shi mouse induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. A total of 28 urinary bladder carcinomas of both transitional cell and squamous cell types were studied. All were invasive (greater than pT3) and high-grade and 10 of them had metastasis. Only two (11%) of 18 primary bladder carcinomas without metastasis foci showed alterations in one or two loci. None of 10 pairs of urinary bladder carcinomas and metastasis foci demonstrated any alterations. In conclusion, MSI which represents a defect in the DNA mismatch repair system is infrequent and therefore unlikely to be a critical step in genesis of invasive mouse urinary bladder carcinomas.

Animals↗

F344/Shi rats bearing type b catalase-1 locus are sensitive to sodium L-ascorbate promotion of two-stage urinary bladder carcinogenesis.

Our previous data showed that F344/DuCrj and LEW/Crj rat strains bearing the type a catalase-1 locus (CS1a) are sensitive to the promoting activity of sodium L-ascorbate (Na-AsA) in 2-stage urinary bladder carcinogenesis, whereas ODS/Shi and WS/ Shi rat strains bearing the type b catalase-1 locus (CS1b) are resistant. In present study, we investigated the susceptibility of F344/Shi rats also bearing the CS1 to the Na-AsA-promoting effects on bladder tumor development. Male rats, 6 weeks old, were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 4 weeks, then fed either basal diet supplemented with 5% Na-AsA or no chemicals for 32 weeks. The rats given BBN alone had a few small carcinomas in the urinary bladder. In contrast, animals administered BBN-Na-AsA had many large carcinomas. Administration of Na-AsA was associated with significant elevation of urinary pH and L-ascorbic acid. The results indicate that F344/Shi rats are sensitive to the promoting effects of Na-AsA on 2-stage urinary bladder carcinogenesis, and thus that the CS1 locus may not influence susceptibility to promotion.

Alleles↗

Possible rare involvement of O6-methylguanine formation as a significant mutational factor in mouse urinary bladder carcinogenesis models.

O6-methylguanine is known as one of the major premutagenic lesions in the human and rodent carcinogenesis process. O6-methylguanine-DNA methyltransferase (MGMT), which repairs methylated guanine bases, might prevent the G:C to A:T transition, and transgenic mice carrying this MGMT gene have been reported to be less sensitive to the carcinogenicity of certain alkylating agents. Here we utilized MGMT transgenic mice to assess the significance of O6-methylguanine formation during urinary bladder carcinogenesis. In experiment 1, 100 and 60 ppm N-butyl-N(4-hydroxybutyl)nitrosamine was given for 20 weeks to transgenic and non-transgenic mice in their drinking water. The incidences of urinary bladder carcinomas were not different between transgenic mice and non-transgenic mice. The mutational spectrum of the p53 gene was evaluated by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. The pattern of p53 mutations of transgenic and non-transgenic mice did not differ, and the frequencies of mutations were 40% and 42%, respectively. G:C to A:T transition mutations were particularly infrequent (1 of 14 mutations, 7%). In experiment 2, N-methyl-N-nitrosourea, which might induce O6-methylguanine in affected alleles, was given once a week, 3 times (total 5 mg) by direct instillation into the urinary bladder through an abdominal incision. No significant neoplastic lesions were detected, although the experiment was limited by severe toxicity of the treatment. p53 immunostaining was done and there was no difference in transgenic and non-transgenic mice. These results suggest that O6-methylguanine formation might not be a significant mutational factor in these mouse urinary bladder carcinogenesis models.

Adenosine Deaminase↗

Host genes affecting survival period of chemically induced bladder cancer in mice.

Treatment of C57BL/6 J (B6) and NON male mice with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) resulted in a high incidence of bladder cancer. The mean survival period, however, differed significantly by strain: 481+/-219 days in B6 (n = 31) and 203+/-119 days in NON (n = 30) (P < 0.0001). Major causes of death were renal failure due to obstruction of the urinary tract, or local invasion of tumors. The fact that the BBN-treated NON x B6 reciprocal F1 mice had survival periods as short as those of the parental NON mice suggests a genetically dominant susceptibility in NON or recessive resistance in B6. A linkage analysis of 248 back-cross mice to B6 suggested at least two quantitative trait loci determining the length of the survival period: one was mapped close to D2Mit260 (logarithm of odds, LOD, score 2.21), a microsatellite marker locus 83 cM from the centromere on chromosome 2, and another was close to D6Mit159, 7 cM from the centromere on chromosome 6 (LOD score 2.51).

Animals↗

Urinary 7alpha-hydroxy-3-oxochol-4-en-24-oic and 3-oxochola-4,6-dien-24-oic acids in infants with cholestasis.

BACKGROUND/AIMS: Urinary 3-oxo-delta4 bile acids have been detected in infants who ultimately died of liver disease. We used qualitative and quantitative methods to compare urinary 3-oxo-delta4 bile acids in liver disease, determining their composition and evaluating the prognostic implication in patients of various ages with various liver diseases. METHODS: Gas chromatography-mass spectrometry was used to measure 3-oxo-delta4 bile acids in the urine of patients and healthy controls. RESULTS: Patients with a deficiency of 3-oxo-delta4-steroid 5beta-reductase and acute hepatic failure exhibited a significantly higher percentage of 3-oxo-delta4 bile acids in total bile acids in urine than the healthy controls or other patient groups, including those with neonatal cholestasis or biliary atresia (p<0.0001). The urinary 3-oxo-delta4 bile acids in patients with 3-oxo-delta4-steroid 5beta-reductase deficiency who had a poor prognosis were mainly 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid. CONCLUSIONS: Our results indicate that an increase in the 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid in the urine of patients with hepatobiliary disease indicates a poor prognosis.

Adolescent↗

Clonidine reduces dopamine and increases GABA in the nucleus accumbens: an in vivo microdialysis study.

The effects of clonidine, an alpha2 adrenoceptor agonist, on extracellular concentrations of dopamine and gamma-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied by using in vivo brain microdialysis. Clonidine (5 microg/kg i.v.) significantly decreased the brain microdialysate concentration of dopamine in the nucleus accumbens up to a maximum of 16% at its peak effect. This effect was inhibited by a dose of idazoxan (10 microg/kg i.v.), an alpha2-adrenoceptor antagonist. which itself did not affect the efflux of dopamine. A smaller dose of clonidine (1 microg/kg i.v.), which had no significant effect on dopamine efflux per se, decreased the dopamine efflux (21% reduction) when given together with an ineffective dose of midazolam (0.075 mg/kg i.v.), a benzodiazepine receptor agonist. The effect of clonidine (5 microg/kg i.v.) on mesolimbic dopamine efflux was abolished by bicuculline (1 mg/kg i.v.), a GABA(A) receptor antagonist, counteracted by beta-carboline-3-carboxylate ethyl ester (beta-CCE, 3 mg/kg i.p.), a benzodiazepine receptor inverse agonist, but not affected by flumazenil (6 microg/kg i.v.), a benzodiazepine receptor antagonist. Clonidine (5 microg/kg i.v.) increased the dialysate concentration of GABA in the nucleus accumbens up to a maximum of 250% at its peak effect, but not in the ventral tegmental area. It is hypothesized that GABA(A) binding sites in the nucleus accumbens form part of the sequence of events that is triggered by clonidine in an alpha2-adrenergic-specific manner and that ultimately results in a decreased release of dopamine in the nucleus accumbens.

Adrenergic alpha-Agonists↗

Interictal change in cardiac autonomic function associated with EEG abnormalities and clinical symptoms: a longitudinal study following acute deterioration in two patients with temporal lobe epilepsy.

The purpose of the present study was to investigate the ictal and interictal changes in cardiac autonomic function (CAF), and the relationship between the interictal change in CAF to the electroencephalogram (EEG) and clinical findings. In two patients with temporal lobe epilepsy (TLE) showing acute deterioration, a quantitative evaluation of their interictal CAF based on heart rate variability and their EEG using spectral analysis was conducted, and the findings compared with repeated clinical evaluations during the recovery period. The ictal heart rate changes and their temporal relationship to ictal discharge were investigated using simultaneous EEG/electrocardiogram (ECG) monitoring in one of the patients. Interictal parasympathetic function was decreased during the period of acute deterioration, but was increased in association with improvements in the EEG and clinical findings. In contrast, the sympathetic function showed no specific changes. The ictal discharges were preceded by a brief bradycardia, with a long delay of up to 40s. The results demonstrated that this decrease in parasympathetic function was closely related to the interictal changes in central nervous system function. On the other hand, the ictal discharges in one of the patients were thought to have caused a transient elevation of parasympathetic function. It is strongly suggested that patients with TLE have interictal as well as ictal changes in CAF that are mediated mainly through the parasympathetic nervous system.

Adult↗

Effectiveness of omeprazole-amoxicillin-clarithromycin (OAC) therapy for Helicobacter pylori infection in a Japanese population.

BACKGROUND: Omeprazole or lansoprazole, amoxicillin, clarithromycin (PPI/AC) therapy has been reported to provide a high cure rate of H. pylori infection with few adverse effects. Effectiveness of H. pylori therapy may vary among different geographic regions and patient populations. However, there are few reports in Japan as to its effectiveness. We have, therefore, studied the effectiveness of H. pylori therapy in a large group of Japanese patients. METHODS: For this study, 366 H. pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia (263 men and 103 women, mean age 48.5 years) were assigned to 6 groups, each receiving a different PPI/AC regimen. Group 1 received omeprazole (OPZ) 20 mg, amoxicillin (AMOX) 1500 mg, and clarithromycin (CAM) 400 mg; Group 2 OPZ 40 mg, AMOX 1500 mg, and CAM 400; and Group 3 OPZ 20 mg, AMOX 2000 mg, and CAM 600 mg daily for 14 days. The group treated with lansoprazole (LPZ) 30 mg, AMOX 1500 mg and CAM 400 mg was used for 14 days in Group 1L. OPZ 20 mg, AMOX 750 mg, and CAM 200 mg were given to Group 4 for 28 days and OPZ 20 mg, AMOX 1500 mg, CAM 400 mg was administered to Group 5 for 7 days. Cure of infection was assessed by 13C urea breath test one month after completion of therapy. RESULTS: Cure rates calculated by excluding the patients who showed borderline value of 13C urea breath test (delta 13C value between 5 and 10% in Groups 1, 1L, 2, 3, 4, and 5 were 82.7% (95% CI; 74-90), 88.9% (76-96), 84.9% (72-93), 81.3% (67-91), 84.6% (72-93), and 85.1% (72-94) on an intention-to-treat basis, and 88% (80-94), 95.2% (84-99), 95.6% (85-99), 90.7% (78-97), 95.7% (85-99) and 88.9% (76-96) on a per-protocol basis, respectively. Adverse effects that affected compliance were observed in 10 of 237 patients on 14-day regiments, one of 47 on a 28-day regimen and one of 46 on a 7-day regimen. CONCLUSION: Two weeks PPI/AC therapy is highly effective for cure of H. pylori infection in the Japanese population. The low dose one month regimen and the one week OAC regimen were also effective in our patient population.

Adult↗

Hemodynamics of a simulation of the vertebrobasilar system using silicone tube.

We investigated the hemodynamics of the vertebrobasilar system (VBS) using a simulation model tube made of silicone which had different diameters between the bilateral vertebral artery (VA) ducts (stenotic and normal VA ducts). Using the ultrasonic Doppler method. the laterality index (L.I.) of the flow velocity in the VA duct was 32.88%. The flow volume of the anterior inferior cerebellar artery duct and the posterior inferior cerebellar artery duct also had significant laterality. By investigating the effects of the rotatory pulse rate and fluid viscosity, a maximal decrease to below 40-50% of the flow volume of the branches, and to below 71.93% in the mean flow velocity of the basilar artery (BA) duct (BA duct) were observed. and the maximum L.I. increased to 43.15%. When the unilateral stenotic VA duct was occluded by clamping (clamping occlusion), the flow volume profiles of the branches were the same as without clamping occlusion. The L.I. showed no significant changes and the maximal decrease in the mean flow velocity of the BA duct was 68.61%. Using the laser Doppler method, the flow velocity distribution of the BA duct was shifted towards the side of the stenotic VA duct. These results suggest that the rheological dynamics in the main vessels can certainly reflect the posterior circulatory dynamics, and that modulating factors also aggravate the hemodynamics of the VBS with this disorder.

Arteries↗

Influence of hyperlipidemia and smoking on age-related changes in caloric response and pure-tone hearing.

To examine the influence of hyperlipidemia and smoking on age-related changes in caloric response and pure-tone hearing, a caloric test and pure-tone audiometry were performed in 14 healthy volunteers and in 78 tinnitus patients without subjective hearing loss. The patients were from 24 to 84 years of age, and were divided into 4 groups: the no-risk group (N group), the smoking alone group (S group), the hyperlipidemia alone group (L group), and the smoking plus hyperlipidemia group (S-L group). Slow phase eye velocity of the caloric nystagmus (SPEV) and average hearing level at high frequencies were compared between the N groups and the other groups. There was a significant difference in SPEV only between the N and S-L groups, but not in the hearing level. This suggests that age-related changes in the caloric response be promoted by atherosclerosis, unlike presbycusis.

Adult↗

[13C]-urea breath test for assessment of cure of Helicobacter pylori infection at 1 month after treatment.

Although the [13C]-urea breath test has been reported to provide high specificity and sensitivity, its reliability in determination of cure, including when and how the assessment of cure is made, is not fully established. Here we evaluate the reliability of judgment of cure after 1 month of therapy using the [13C]-urea breath test, including the appropriate time to assess its cure. Our subjects were 199 H. pylori-infected patients (144 men and 55 women; 50.5+/-0.76 years) who underwent cure therapy, took the breath test at 1 month, and underwent both the breath test and invasive tests using endoscopy at 6 months after completion of therapy. Accuracy of the breath test in judgment of cure at 1 month was investigated by comparing the results at 1 month with those at 6 months when cut-off value of the breath test was set at 5 per thousand. Chronologic alterations of the delta13C value were also analyzed in cured patients who underwent the breath test at 1, 3, and 6 months. In 167 (94.9%) of 176 patients whose breath test values were less than 5 per thousand, cure was reconfirmed at 6 months. In 14 (60.9%) of 23 patients whose values were greater than 5 per thousand, cure was demonstrated at 6 months. The mean delta13C values of 33 cured patients who took the breath test at 1 month and repeated the breath test at 3 and 6 months for any reasons were 4.14+/-0.74 per thousand, 2.02+/-0.23 per thousand, and 1.72+/-0.19 per thousand, respectively, and the value at 3 months was significantly smaller than that at 1 month. The reliability of assessment of cure by only the breath test at 1 month was sufficiently high (94.9%) once the patients were judged to be cured. However, because the breath test at 1 month yielded a high false-positive rate and the breath test values at 3 and 6 months were similar, evaluation of cure of H. pylori infection by the [13C]-urea breath test should preferably be done at 3 months after treatment to minimize false-positive results, or the concept of a borderline group should be established for patients with positive but relatively high delta13C values (5-10 per thousand) who repeated the breath test 3 months after treatment.

Breath Tests↗

Usefulness of the [13C]-urea breath test for detection of Helicobacter pylori infection in fasting patients.

Most of the reported [13C]-urea breath test procedures use a test meal, which is believed to assist in the spread of the [13C]-urea solution into the entire stomach, as results without a test meal may mainly reflect urease activity in the antrum.Yet, procedures for the [13C]-urea breath test and interpretation of the obtained 13C excess value have not been well established. We carried out the present study to validate the usefulness of the [13C]-urea breath test in fasting subjects and to establish cut-off values. [13C]-Urea breath tests were performed on 258 Helicobacter pylori-positive and 151 -negative subjects (247 H. pylori positive and 26 negative prior to any H. pylori cure treatment and 125 H. pylori negative and 11 positive after undergoing H. pylori cure treatment). The breath test procedure was performed under the following conditions: an 8 h fast, mouth washing before and after dosing, administration of 100 mg [13C]-urea, collection of breath sample in a plastic bag, a baseline and a 20 min sampling point and subject in a sitting position. Delta-13C at the 20 min sampling point in H. pylori-positive and -negative subjects was 31.0+/-1.25 and 1.6+/-0.11%, respectively. Although the mean delta13C value was greatest in duodenal ulcer or ulcer scar patients, there were no significant differences among mean delta13C values in the various diseases. From Receiver Operator Characteristic curves and calculation of accuracy of the test, a cut-off value of 5.0% is considered to be appropriate for diagnosis of H. pylori infection, which provides 96.7% specificity and 96.5% sensitivity, suggesting that the [13C]-urea breath test in the fasting state is as effective in detecting the presence of H. pylori as other reported methods.

Adult↗

[Report of surveillance on streptococcal toxic shock syndrome in Japan and presentation of the criteria].

A survey was made on the situation of Group A Streptococcal toxic shock syndrome (STSS) based on questionnaires. The survey was divided into two parts. The first survey was done by sending out an outline of the STSS inquiring if any STSS cases were observed by mail to university hospitals, residence training hospital and other major hospitals totaling 2512 institutes. The second survey was subsequently done to the institutes that had STSS cases asking for the clinical course, data and sampling of the bacteria. The diagnosis of STSS was confirmed based on the diagnostic criteria induced by the working group of the United States. We have found 97 cases of STSS which 48.5% had fatal outcomes. There was no significant sex difference in the onset or the mortality rate. It occurred more in the older population, and occurred through out Japan but was not found to be epidemic. The first case was backed in 1978 and it began to increase since 1993, reaching its peak in 1994 and now decreasing in number. Most of the isolated Group A streptococcus were of type M1 and M3. We have modified the United States diagnostic criteria creating a new Japanese criteria, which includes the symptoms of the central nervous system in the term MOF. The aim for the Japanese criteria is to search for the etiology of the disease. The Japanese criteria requires that the disease progresses rapidly and that the patient be free from any conditions that might suppress the immunal system.

Adolescent↗

Assimilation of cellooligosaccharides by a cell surface-engineered yeast expressing beta-glucosidase and carboxymethylcellulase from aspergillus aculeatus

Since Saccharomyces cerevisiae lacks the cellulase complexes that hydrolyze cellulosic materials, which are abundant in the world, two types of hydrolytic enzymes involved in the degradation of cellulosic materials to glucose were genetically co-immobilized on its cell surface for direct utilization of cellulosic materials, one of the final goals of our studies. The genes encoding FI-carboxymethylcellulase (CMCase) and beta-glucosidase from the fungus Aspergillus aculeatus were individually fused with the gene encoding the C-terminal half (320 amino acid residues from the C terminus) of yeast alpha-agglutinin and introduced into S. cerevisiae. The delivery of CMCase and beta-glucosidase to the cell surface was carried out by the secretion signal sequence of the native signal sequence of CMCase and by the secretion signal sequence of glucoamylase from Rhizopus oryzae for beta-glucosidase, respectively. The genes were expressed by the glyceraldehyde-3-phosphate dehydrogenase promoter from S. cerevisiae. The CMCase and beta-glucosidase activities were detected in the cell pellet fraction, not in the culture supernatant. The display of CMCase and beta-glucosidase proteins on the cell surface was confirmed by immunofluorescence microscopy. The cells displaying these cellulases could grow on cellobiose or water-soluble cellooligosaccharides as the sole carbon source. The degradation and assimilation of cellooligosaccharides were confirmed by thin-layer chromatography. This result showed that the cell surface-engineered yeast with these enzymes can be endowed with the ability to assimilate cellooligosaccharides. This is the first step in the assimilation of cellulosic materials by S. cerevisiae expressing heterologous cellulase genes.

Journal Article↗

Temporal lobe epilepsy in a genius of natural history: MRI volumetric study of postmortem brain.

Kumagusu Minakata (1867-1941), a Japanese genius devoted to natural history and folklore, is famous for his immense range of works, including his discovery of many new varieties of mycetozoa, or slime molds. His diary reveals that he was affected by epilepsy. In this study of his brain, we adopted a method of measuring the volume of the hippocampi by MRI of postmortem brain and found evidence of right hippocampal atrophy. This finding, together with the striking parallels between his behavior and the known behavioral syndrome in temporal lobe epilepsy (TLE), suggests that he was affected by TLE. The postmortem imaging analysis of brain, as performed in this study, offers a bridge between neuroscience and classic psychopathologic approaches to the creativity of geniuses.

Aged↗

Effect of intravenous vasopressin on endocochlear potential and systemic blood pressure in the guinea pig.

The effects of intravenous arginine-vasopressin (AVP) on the endocochlear potential (EP) and systemic blood pressure (BP) were examined in the guinea pig. Intravenous AVP (10(-7) M) elevated BP significantly but did not change EP. AVP (10(-8) M) produced a significant decrease in the amplitude of EP but did not change mean blood pressure significantly. AVP at 10(-9) M did not affect EP or BP. These results suggest that intravenous AVP might have an inhibitory effect on EP.

Animals↗

Inner ear blood flow in the rat after unilateral arterial occlusion in the vertebrobasilar arterial system.

It is generally accepted that certain kinds of vertigo and hearing disturbances are caused by blood flow insufficiency in the vertebrobasilar arterial system. Using the microsphere method we investigated whether unilateral vertebral artery or unilateral posterior inferior cerebellar artery occlusion could cause an imbalance between right and left inner ear blood flow in rats. We also studied the differential vulnerability between blood flow in the cochlea and in the ampullae of the three semicircular canals. We counted the numbers of microspheres distributed to the cochlea (CO) and microspheres distributed to three ampullae of semicircular canals (SC) under a microscope with the surface preparation method. The results were as follows: i) no imbalances were observed between bilateral CO or SC even in animals with arterial occlusion, and ii) the CO/SCs of animals with arterial occlusion were not significantly different from that of the control animals. These findings suggest that total inner ear blood flow over a certain period of time was even between the ears bilaterally even in animals with arterial occlusion. The blood flow in the ampullae of the three semicircular canals was not more or less affected by arterial occlusion than the blood flow in the cochlea.

Animals↗