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Biomedical subjects

M Nagao

Publications and source records attributed to M Nagao.

At least 163 records · Page 9Linked to original sources

Cytochrome P4501A1 and glutathione S-transferase M1 genotypes as risk factors for prostate cancer in Japan.

BACKGROUND: The p53 mutation spectrum of prostate cancers developing in Japan indicates a role for environmental factors. This suggests there might be differences in susceptibility due to genetic polymorphisms in metabolic activation enzyme genes. We analyzed genetic polymorphisms of the xenobiotic-metabolizing enzymes, CYP1A1 and GSTM1. METHOD: Genotyping of CYP1A1 and GSTM1 was investigated by using allele-specific PCR in 115 prostate cancer (PCa) patients and 204 control patients. RESULTS: The CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR = 2.6; 95% CI = 1.11-6.25) and the Ile/Val genotype showed a similar tendency (OR = 1.4; CI = 0.86-2.29). Individuals with the GSTM1 (0/0) genotype demonstrated a slightly increased risk (OR = 1.3; CI = 0.82-2.04). The combination of the CYP1A1 Val allele and GSTM1 (0/0) genotype was associated with a higher risk (OR = 2.3; CI = 1.18-4.48) than the CYP1A1 Val allele alone. When cases were analyzed by age at initial diagnosis, the relative risks with both the CYP1A1 Val allele and the GSTM1 (0/0) genotype were higher in the young group than in the old group (CYP1A1; OR = 1.7, CI = 0.89-3.17: GSTM1; OR = 1.6, CI = 0.84-2.99). The frequency of the GSTM1 (0/0) genotype was also higher in patients with advanced stage disease. In stage D, the OR was 1.7 with a CI of 0.93-3.17 and in stages A and B, the OR was 0.8 with a CI of 0.40-1.62. CONCLUSIONS: These results suggest that CYP1A1 and GSTM1 polymorphisms are linked to a propensity for PCa development.

Aged↗

DNA adduct level induced by 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline in Big Blue mice does not correlate with mutagenicity.

In previous experiments we analyzed the mutant frequency (MF) and mutational types in various organs of lacI transgenic mice which were fed a diet containing 300 p.p.m. 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a food-borne mutagen/carcinogen. To clarify the relationships between mutational type and adduct molecular species and between adduct level and MF we analyzed adducts in the same DNA samples. The DNA adduct in the liver, heart, colon, forestomach and bone marrow was determined by the modified intensification method of 32P-post-labeling at time points 1, 4 and 12 weeks. Only a single spot corresponding to N2-(deoxyguanosin-8-yl)MeIQ 5'-monophosphate was detected in DNA from all organs at all time points examined, with a recovery of 48%. The difference in mutation type between bone marrow and other organs detected in the previous experiment was not explained by adduct molecular species. At 4 and 12 weeks administration the adduct levels were highest in the liver and then heart, colon, forestomach and bone marrow in decreasing order, with values of 28.3, 8.4, 3.3, 1.3 and 0.4 molecule/10(7) nucleotides at 12 weeks. Based on our previously reported data, lacI MF was highest in the colon and those in the liver, bone marrow and forestomach were 10-60% of that of the colon; no increase in MF was detected in the heart, where no DNA replication is expected except for vascular endothelial cells. There was no direct relationship between MF and adduct level. The MF may be the product of adduct level and cell proliferation rate.

Animals↗

Loss of cholinergic synapses on the spinal motor neurons of amyotrophic lateral sclerosis.

The expression of vesicular acetylcholine transporter (VAChT) was examined immunohistochemically in the cholinergic synapses on the spinal motor neuron of the patient with sporadic amyotrophic lateral sclerosis (SALS). VAChT immunoreactive synapses were depleted on surviving motor neurons in SALS, while synaptophysin immunoreactivity was undiminished on the same neurons. This discrepancy suggests that in SALS, loss of cholinergic input on lower motor neurons is an early event, and may be part of the cause of death of those motor neurons.

Acetylcholine↗

Linkage mapping of the Bra, Brb and Brg genes for rat protein phosphatase 2A 55 kDa B-regulatory subunit isotypes.

We previously identified the rat Bra, Brb and Brg genes, which encode alpha, beta and gamma isotypes of the 55 kDa B-regulatory subunit of protein phosphatase 2A. Polymerase chain reaction-single strand conformation polymorphism analysis in the present study identified polymorphisms in Bra, Brb and Brg between the ACI and BUF, ZI and TM, and BN and WTC strains, respectively. Linkage analysis using mapping panels composed of F2 or back-crosses of these strains allowed Bra, Brb and Brg to be assigned to chromosomes 15, 18 and 14, respectively. Furthermore, it was revealed that Bra is located close to the Rb1 locus. Using polymorphism in Bra, loss of heterozygosity (LOH) was analyzed for rat mammary tumors induced in (SD x F344) F1 female rats by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and a typical mammary carcinogen, 7,12-dimethylbenz[a]anthracene. No LOH was detected at the Bra locus.

9,10-Dimethyl-1,2-benzanthracene↗

Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.

We report a girl with oral, facial, and digital anomalies including multiple alveolar frenula, lobulated tongue with nodules, a posterior cleft palate, hypertelorism, a prominent forehead with a large anterior fontanelle, and postaxial polydactyly in both hands and the right foot, features compatible with the oral-facial-digital syndrome (OFDS). In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker malformation and retrobulbar cysts were observed on MRI. These additional malformations have not been reported in OFDS type IX. The frequent apnoeic spells which occurred immediately after birth were relieved after cystoperitoneal shunt implantation for hydrocephalus. Considering our case and previous reports of OFDS type IX, including two male sibs, a boy born to consanguineous parents, and three females, inheritance is probably autosomal recessive.

Dandy-Walker Syndrome↗

Distal sensory axonopathy after sarin intoxication.

A 51-year-old man inhaled sarin during a terrorist attack on the Tokyo subway system and died 15 months later. Neuropathologic examination revealed marked nerve fiber decrease in the sural nerve, moderate nerve fiber loss in the sciatic nerve, and unremarkable dorsal root ganglia, dorsal roots, and posterior column of the spinal cord. This pathology is consistent with dying-back degeneration of the peripheral nervous system and could represent a late sequela of sarin intoxication.

Fatal Outcome↗

Quantitative analysis of pulmonary emphysema: three-dimensional fractal analysis of single-photon emission computed tomography images obtained with a carbon particle radioaerosol.

OBJECTIVE: The purpose of this study was to quantify the heterogeneous distribution of a carbon particle radioaerosol in the lungs of patients with pulmonary emphysema using single-photon emission computed tomography (SPECT) and fractal analysis. SUBJECTS AND METHODS: Ventilation SPECT was performed on 19 patients with pulmonary emphysema, seven patients with suspected pulmonary emphysema, and 14 healthy volunteers. We delineated the lungs using five cutoff levels (15%, 20%, 25%, 30%, and 35% of the maximal pixel radioactivity) and measured the total number of pixels in the areas surrounded by the contours obtained with each cutoff level. We calculated fractal dimensions from the relationship between the total number of pixels and cutoff levels transformed into logarithms. RESULTS: The fractal dimensions increased with the severity of pulmonary emphysema. The fractal dimensions for patients with pulmonary emphysema, patients with suspected pulmonary emphysema, and healthy volunteers were 2.03+/-0.61 (mean +/- SD), 0.77+/-0.09, and 0.59+/-0.06, respectively. A significant difference (p < .0005) in the fractal dimension was found when any of these three groups was compared with any other group of subjects. CONCLUSION: Three-dimensional quantitative evaluation of the emphysematous lung was possible using SPECT and fractal analysis. Our results suggest that fractal analysis can quantify the heterogeneity of the distribution of a carbon particle radioaerosol in the lung. Fractal analysis appears to be applicable for routine clinical use because it is simple and the fractal dimensions can be obtained easily without using special software.

Aged↗

[Oral conditions of inhabitants in Tokashiki Island, Okinawa].

The Department of Health of Okinawa Prefecture with the cooperation of the Ministry of Health and Welfare and eight Dental Schools in Japan, is performing dental treatment and oral health care on inhabitants in areas of Okinawa where no dentists are present. We were asked to offer dental treatment and oral health care for the inhabitants of Tokashiki Island, Okinawa from June 30 to July 29, 1997. The DMF rates of school children of Tokashiki Island was much higher than the average rates in Japan. Among the treatment procedures, conservative treatment was 72.5%, most of which was composite resin filling. Most middle-aged persons had severe periodontal disease rather than severe dental caries. Patients, who suffered from severe dental caries chose extraction of their teeth rather than conservative treatment. The denture wearers of Tokashiki Island used their dentures longer than those who visited our Prosthodontic Department. They were not necessarily dissatisfied with their dentures, but their alveolar ridges were absorbed extensively. These conditions could be due to not only patients' consciousness but also the lack of dental hygiene education. It seems that primary prevention and higher dental hygiene education are needed for the inhabitants of Tokashiki Island where dental treatment must be done in a short time.

Adolescent↗

Dynamic viscoelastic properties of models composed of posterior denture teeth and denture base resin.

The purpose of this investigation was to compare the dynamic viscoelastic properties of various models composed of denture teeth and heat-cured denture base resin. The specimens were porcelain and resin teeth mounted in denture base resin. Compressive dynamic stiffness and phase differences were measured with a viscoelastic spectrometer. Measurements of the viscoelastic frequency spectrum based on the fast Fourier transform of displacement to applied random forces were analyzed with a spectrum analyzer. The stiffness of the specimens was independent of the frequency. The stiffness of the porcelain specimens was higher than that of the resin ones measured under the same conditions. The phase lag of the specimens was dependent on the frequency. The phase lag of the porcelain specimens was lower than that of the resin ones measured under the same conditions. This study suggested that the acrylic resin teeth had greater toughness and higher shock-absorbing ability than the porcelain teeth, and that the porcelain teeth were more brittle than the acrylic resin ones, whether the teeth were isolated or in dentures.

Acrylic Resins↗

[Urgent cesarean section under combined spinal and epidural anesthesia in a patient with aortitis syndrome].

We report the anesthetic management of a patient with aortitis syndrome using combined spinal and epidural anesthesia. A 28-year-old gravida with aortitis syndrome accompanied by faints was scheduled for an urgent cesarean section. Combined spinal and epidural anesthesia was thought to be better for this case in order to monitor the cerebral circulation by her consciousness level and to reduce the hemodynamic change during surgery as compared to spinal or epidural anesthesia alone. After inserting an epidural catheter at the Th 12/L 1 interspace, spinal anesthesia was performed with 1.5 ml of 0.3% dibucaine at the L 4/L 5 interspace. The level of analgesia was under L 1 with the pinprick method 10 min after the spinal anesthesia. Next, 5 ml of 1.5% mepivacaine was injected through the epidural catheter. The level of analgesia reached to Th 6 without major hemodynamic changes. A healthy 2740 g infant was delivered and she had an uneventful recovery. We conclude that combined spinal and epidural anesthesia is useful in a patient with aortitis syndrome undergoing an urgent cesarean section in order to monitor the cerebral circulation by the consciousness level and to reduce the hemodynamic change.

Adult↗

[Anesthetic management using propofol and fentanyl of a patient with concealed Wolff-Parkinson-White syndrome].

We report the anesthetic management using propofol and fentanyl of a patient with concealed Wolff-Parkinson-White syndrome. A 62-year-old patient was diagnosed as having concealed Wolff-Parkinson-White syndrome by electrophysiologic study 7 years before. He felt palpitation in spite of administration of disopiramide. He was scheduled for a microsurgery of the larynx. After premedication with atropine 0.5 mg and hydroxyzine 50 mg i.m. 30 min prior to anesthesia, anesthesia was induced with a step down method of propofol (20-->12-->8 mg.kg-1.h-1) and fentanyl 0.15 mg Anesthesia was maintained with 6 to 8 mg.kg-1.h-1 of propofol and periodic administration of fentanyl. Immediately after the insertion of a laryngoscope, blood pressure increased but systolic blood pressure was maintained from 120 to 140 mmHg during the procedure. Thereafter anesthesia remained stable and paroxysmal tachycardia did not appear. The postoperative course was uneventful. We conclude that anesthesia using propofol and fentanyl is useful in a patient with Wolff-Parkinson-White syndrome in order to prevent paroxysmal tachycardia.

Anesthesia, Intravenous↗

Effects of gender and species on spectra of mutation induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the lacI transgene.

Feeding of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to F344 rats induces colon tumors specifically in male rats. Mutant frequencies and mutational spectra of the lacI transgene were studied in male and female Big Blue transgenic rats after feeding 400 ppm of PhIP in the diet for 60 days. Mutant frequencies in the colon mucosa were increased 20-25 times compared with those of the control rats, being 661.4 +/- 33.3 x 10(-6) and 718.2 +/- 16.9 x 10(-6) in males and females, respectively. No significant differences in types and distribution of the mutations were detected between males and females. One-base deletions were the most frequent mutation, including the characteristic guanine deletion at 5'-GGGA-3' which is also seen in the Apc gene of rat colon cancers induced by PhIP. Comparison of the lacI mutations in the rat colon with those previously identified in the mouse colon showed that the rate of G to T transversions was significantly higher in the mouse. This is the first report stating that there exist differences in the mutation specificity on the same gene, among mammalian species. However, the characteristic guanine deletion was recovered in both the mouse and the rat. These findings do not offer a mechanistic explanation of the gender specificity of PhIP-induced colon cancer in rats, though the universality of the guanine deletion suggests that this alteration may prove a useful indicator of human exposure.

Animals↗