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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 145 records · Page 8Linked to original sources

[Student evaluation of the curriculum coordination between two affiliated departments (environmental health versus preventive medicine and community health) in undergraduate medical education].

In order to assess the degree of curriculum coordination between the course for environmental health (3rd year, 100 hrs.) and that of preventive medicine and community health (4th year, 160 hrs.) in a medical school founded 1978, the responses for the related questions in the students evaluations (anonymous) were monitored annually from 1987-94. The former is a course that mainly deals with environmental health, occupational hygiene, nutrition and food poisoning, while the latter deals with health statistics, epidemiology, health promotion and health education, community health (including maternal and child health, school health, occupational health, gerontological health etc.) and health administration. Approximately 60% of the 786 medical students responded affirmatively as "fairly well coordinated" and less than 5% responded negatively as "not well coordinated". Analysis of the free answers columns shows that the characteristic contrasts between two courses/disciplines as each of the courses had been designed for are maintained and can be obtained from the courses. These results show the necessity of similar evaluative analyses for other courses to ensure appropriate division and coordination between affiliated courses in the undergraduate medical education program.

Curriculum↗

Chlorogenic acid as a natural scavenger for hypochlorous acid.

The effect of chlorogenic acid (CGA) on the killing of Escherichia coli by hypochlorous acid (HOCI) was examined. CGA prevented E. coli from bactericidal action of HOCI in a concentration-dependent manner. HOCI reacted rapidly with CGA. By comparison with the one- and two-electron oxidation products produced by peroxidase and phenolase reactions, respectively, the main product was identified as o-quinone of CGA via the formation of o-semiquinone of CGA as an intermediate The quinone form of CGA reacted further with HOCI to yield unstable product(s).

Blood Bactericidal Activity↗

The suppression of the N-nitrosating reaction by chlorogenic acid.

N-Nitrosation of a model aromatic amine (2,3-diamino-naphthalene) by the N-nitrosating agent produced by nitrite in acidic solution was inhibited by a polyphenol, chlorogenic acid, which is an ester of caffeic acid quinic acid. Caffeic acid also inhibited the N-nitrosation, but quinic acid did not. 1,2-Benzenediols and 3,4-dihydroxybenzoic acid had inhibitory activities. Chlorogenic acid, caffeic acid, 1,2-benzenediols and 3,4-dihydroxybenzoic acid were able to scavenge the stable free radical, 1,1-diphenyl-2-picrylhydrazyl. Chlorogenic acid was found to be nitrated by acidic nitrite. The kinetic studies and the nitration observed only by bubbling of nitric oxide plus nitrogen dioxide gases indicated that the nitrating agent was nitrogen sesquioxide. The observations showed that the mechanism by which chlorogenic acid inhibited N-nitrosation of 2,3-diamino-naphthalene is due to its ability to scavenge the nitrosating agent, nitrogen sesquioxide. Chlorogenic acid may be effective not only in protecting against oxidative damage but also in inhibiting potentially mutagenic and carcinogenic reactions in vivo.

2-Naphthylamine↗

Cytogenetic and immunologic identification of clonal expansion of stem cells into T and B lymphocytes in one Atomic-bomb survivor.

Chromosome aberration frequency in peripheral blood lymphocytes is elevated in radiation-exposed people, and identical karyotypic changes are not infrequently encountered in one blood sample as well as in separate samples from the same donor. Such clonal propagation originates either from a single immature stem cell able to expand and differentiate into several cell types or from a single mature lymphocyte able to expand after antigen stimulation in vivo. In the present study, a total 71 T-lymphocyte and 58 B-lymphocyte colonies were established from one atomic-bomb survivor, who showed a persistent clonal aberration t(4;6), t(5;13) in phytohemagglutinin culture of peripheral lymphocytes. Nearly 10% of the colonies (6 T-lymphocyte and 7 B-lymphocyte colonies) showed the same chromosome abnormality. Southern blot analyses of the T-cell-receptor or Ig heavy-chain gene showed all different rearrangement patterns among T- or B-lymphocyte colonies, respectively. Thus, the chromosome aberration occurred in a precursor cell before differentiation into T and B lineages and was not derived from monoclonal proliferation of mature T or B lymphocytes in the periphery. To confirm the issue, cells from erythroid burst-forming unit (BFU-E) colonies were examined by the chromosome-painting method. Two translocations, one between chromosomes 5 and 13 and the other between chromosomes 4 and one of group C, perfectly consistent with the t(4;6), t(5;13), were found in about 10% of the cells. The results imply that a single stem cell of an adult is capable of generating long-lived myeloid and lymphoid progeny amounting to several percent of the total population of circulating lymphocytes and hematopoietic progenitors.

Aged↗

Potentiating effects of methamphetamine on the hyperactivity of microencephalic rats treated prenatally with methylazoxymethanol: possible implication of hyperdopaminergia.

Microencephalic rats induced by methylazoxymethanol (MAM) were observed to have notable hyperactivity compared to control rats, as measured by several behavioral parameters in an automated field apparatus. Acute injection of the stimulant drug, methamphetamine (MAP), produced an increase in the incidence of locomotion and rearing in control rats, and this stimulatory effect of MAP on motor activity was markedly potentiated in MAM rats. Chronic MAP treatment did not change D1 or D2 dopamine receptor densities in either control or MAM rats. From these results, it was suggested that augmented dopaminergic functions may contribute to the hyperactivity seen in MAM rats.

Alkylating Agents↗

Comparison of equations for predicting bound serum concentrations of carbamazepine and carbamazepine-10, 11-epoxide after polytherapy in patients with epilepsy.

In a previous study, an equation with in vivo population binding parameters of carbamazepine and carbamazepine-10, 11-epoxide (CBZ-E) to serum proteins for the relation between unbound and bound serum concentrations was defined. A review by Pynnönen indicates that the average bound/unbound plasma fraction ratio is 3.0 for carbamazepine and 1.0 for CBZ-E. In this study, the ability of equations with in vivo population binding parameters of the previous study (method 1) or with the average bound/unbound plasma fraction ratio of 3.0 of Pynnönen (method 2) to predict the bound serum carbamazepine concentration was retrospectively evaluated using 85 serum samples from 46 patients with epilepsy taking carbamazepine polytherapy. In 21 serum samples from 16 patients, the ability of these equations to predict bound serum CBZ-E concentration was also determined with in vivo population binding parameters from the previous study (method A) or with the average bound/unbound plasma fraction ratio of 1.0 of Pynnönen (method B). Mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated for each method, and these values served as a measure of prediction bias and precision. Method 1 showed a bias to overpredict bound serum carbamazepine. The MAE and RMSE were significantly smaller with method 2 (MAE = 2.4 mumol/L; RMSE = 3.2 mumol/L) than with method 1 (MAE = 4.1 mumol/L; RMSE = 4.8 mumol/L). Method 2 was superior to method 1 in terms of accuracy and precision. For bound CBZ-E prediction, method B had a bias to underprediction. The MAE and RMSE were smaller with method A (MAE = 0.581 mumol/L; RMSE = 0.796 mumol/L) than with method B (MAE = 0.724 mumol/L; RMSE = 0.905 mumol/L). Method A was superior to method B in terms of accuracy and precision.

Adolescent↗

Evaluation of equations for unbound serum concentration prediction of carbamazepine and carbamazepine-10,11-epoxide in polytherapy pediatric patients with epilepsy.

We retrospectively evaluated the ability of equations with in vivo population binding parameters of our previous study (Method 1) or an average unbound fraction of 0.25 of Pynnönen (Method 2) to predict the unbound serum carbamazepine (CBZ) concentration in 50 serum samples from 28 polytherapy pediatric patients with epilepsy. In 12 serum samples from 10 patients, the ability of equations for unbound serum carbamazepine-10,11-epoxide (CBZ-E) concentration prediction was also determined in predictive performance with in vivo population binding parameters of our previous study (Method A) or an average unbound fraction of 0.5 of Pynnönen (Method B). Mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated for each method, and these values served as a measure of prediction bias and precision. Method 1 shows a bias to underpredict unbound serum CBZ. The MAE and RMSE were lower in Method 2 (MAE = 0.696 microM, RMSE = 0.912 microM) than in Method 1 (MAE = 0.946 microM, RMSE = 1.138 microM). Method 2 is superior to Method 1 in accuracy and precision. The effects of antiepileptic co-medications on predictive performance of Method 1 are relatively larger in a co-medicated group of serum samples with valproic acid (n = 33, MAE = 0.994 microM, RMSE = 1.211 microM) than in a group of serum samples without valproic acid co-medication (n = 17, MAE = 0.853 microM, RMSE = 0.979 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on toluene metabolism in humans.

In this study, we evaluated the effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on the toluene metabolism. The study subjects were 92 male workers who handle toluene in a printing factory, an electrical parts factory, and a painting workplace in Japan. Their exposure levels to toluene were monitored using the diffusion-type sampler. Benzyl alcohol concentrations in their blood and hippuric acid (HA) and creatinine concentrations in their urine at the end of a workshift were determined. The genotype of ALDH2 was classified into the homozygous genotype of a normal ALDH2 gene (NN), the homozygous genotype of an inactive ALDH2 gene (DD), and the heterozygous genotype of normal and inactive ALDH2 genes (ND). The genetic polymorphism of CYP1A1 and CYP2E1 were also determined by restriction fragment length polymorphism (RFLP). A strong correlation between the personal exposure level and the urinary HA concentration was observed. Regression lines were calculated after being divided by the five factors, i.e., ALDH2, CYP1A1, CYP2E1, smoking, and drinking. The HA formation from toluene was significantly (p < 0.001) different among the genotypes of ALDH2. The slopes of the regression lines decreased from NN to ND to DD in this order. The benzyl alcohol concentration in the blood of the DD group was significantly higher than that found in the NN and ND groups. This result demonstrates that ALDH2 polymorphism affects the oxidation of benzyl alcohol to benzoic acid. The toluene metabolism was also affected by CYP1A1 polymorphism. The slope for the Ile/Ile (the predominant homozygous allele) group was significantly lower than that for the Ile/Val (the heterozygous allele) and Val/Val (the rare homozygous allele) group after correction for creatinine. A drinking habit significantly (p < 0.05) reduced urinary HA concentration in the NN group. A smoking habit also significantly (p < 0.05) reduced urinary uncorrected HA concentration in both the NN and ND groups. In a multiple regression analysis, ALDH2 and the drinking habit were significantly (p < 0.01) associated with HA excretion after toluene exposure with and without correction for creatinine, and the corrected HA concentration was also significantly (p < 0.01) increased in the Ile/Val and Val/Val group of CYP1A1. The smoking habit reduced the corrected HA concentration (p < 0.05); however, the polymorphism in the 5'-flanking region of CYP2E1 did not affect HA appearance in urine.

Adult↗

Interlaboratory quality control and status of n-hexane biological monitoring in Japan.

This paper reports the problem of interlaboratory quality control and the actual condition of biological monitoring of n-hexane among the seven major laboratories specializing in clinical chemistry tests, where more than 80% of the total urine specimens in Japan have been analyzed after the beginning of biological monitoring of n-hexane in 1989. First, transportation conditions of urine specimens and transportation effects on measurement results were studied. The seven major laboratories carried urine specimens at distances of more than 450 km from the University of Occupational and Environmental Health (UOEH) to the respective laboratories and had at least one transit terminal where specimens from various areas were collected and transferred to the analytical laboratories. All laboratories used cooler boxes with dry ice or ice bars and stored the specimens in freezers or refrigerators. Specimens arrived at the final destinations within 24 hours. The transportation from institutes for health examination to the laboratories did not affect the measurement results of 2,5-hexanedione (HD), a determinant of n-hexane biological monitoring. Interlaboratory cross-checks were performed among the seven major laboratories and four institutes for occupational health examination that have their own analytical laboratories. All of the laboratories analyzed HD by acid hydrolysis (pH < 1.0); interlaboratory differences were recognized at the first cross-check. After some laboratories intensified gas chromatography (GC) maintenance and changed to a new column, the interlaboratory variation lessened.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Monitoring↗

Biological monitoring of occupational exposure to methyl ethyl ketone in Japanese workers.

The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toluene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples. At the end of the workshift, urine samples were collected to determine the urinary MEK, hippuric acid (HA), and creatinine, and blood samples were also collected at the same time for determination of MEK. The concentrations of urinary MEK ranged from 0.20 to 8.08 mg/L with a mean of 1.19 mg/L and significantly correlated with TWA concentrations of MEK in the air with a correlation coefficient of 0.889 for uncorrected urine samples. The concentration of MEK in the blood was also significantly correlated with the TWA concentration of MEK with a correlation coefficient of 0.820. From these relationships, MEK concentrations in urine and blood corresponding to the threshold limit value-TWA (200 ppm; ACGIH 1992) were calculated to be 5.1 mg/L and 3.8 mg/L as a biological exposure index (BEI), respectively. Although the BEI for urinary MEK obtained from the present study was higher than that of previous reports and ACGIH's recommendation (2.0 mg/L), the BEI agreed well with a previous study in Japan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese.

Isoleucine (Ile)-valine (Val) polymorphism, which is caused by a point mutation from A to G in exon 7, is reported to be associated with an elevated risk of lung cancer among Japanese. Because CYP1A1 catalyzes bioactivation of environmental procarcinogens, such as benzo[a]pyrene, it is very important to study the clinical meaning of Ile-Val polymorphism using an epidemiological study. In an epidemiological study, easy, economical, rapid and reliable identification of the CYP1A1 genotype is necessary. The present study shows that the new method, designed restriction fragment length polymorphism (designed RFLP), can detect Ile-Val polymorphism of CYP1A1. The Ile-Val polymorphism detected using this new method was consistent with that found by the allele-specific PCR amplifications (ASA) method in six cases tested. This new method detected Ile-Val polymorphism of CYP1A1 using 240 healthy Japanese who lived in the northern Kyusyu region. The frequency of the genotypes was as follows: Ile/Ile 159 (66.2%); Ile/Val, 65 (27.1%); Val/Val, 16 (6.7%). The frequency of the Ile gene was 0.798 and that of the Val gene, 0.202. There was no difference in Ile-Val polymorphism based on sex or age. Racial differences influenced the distribution of this polymorphism, but Japanese regional differences did not. Since this new method, designed RFLP, is rapid, reliable and suitable for large-scale screening of polymorphisms, it may be used routinely to detect Ile-Val polymorphism of CYP1A1. Furthermore, it will help to evaluate the relationship between CYP1A1 polymorphism and individual sensitivity to xenobiotics that may affect the incidence of lung cancer.

Adult↗

Distribution of various nickel compounds in rat organs after oral administration.

In this study, eight kinds of nickel (Ni) compounds were orally administered to Wistar male rats and the distribution of each compound was investigated 24 h after the administration. The Ni compounds used in this experiment were nickel metal [Ni-M], nickel oxide (green) [NiO(G)], nickel oxide (black) [NiO(B)], nickel subsulfide [Ni3S2], nickel sulfide [NiS], nickel sulfate [NiSO4], nickel chloride [NiCl2], and nickel nitrate [Ni(NO3)2]. The solubilities of the nickel compounds in saline solution were in the following order; [Ni(NO3)2 > NiCl2 > NiSO4] >> [NiS > Ni3S2] > [NiO(B) > Ni-M > NiO(G)]. The Ni level in the visceral organs was higher in the rats given soluble Ni compounds; Ni(NO3)2, NiCl2, NiSO4, than that in the rats receiving other compounds. In the rats to which soluble Ni compounds were administered, 80-90% of the recovered Ni amounts in the examined organs was detected in the kidneys. On the other hand, the Ni concentration in organs administered scarcely soluble Ni compounds; NiO(B), NiO(G), and Ni-M were very low. The estimated absorbed fraction of each Ni compounds was increased with the increase of the solubility. These results suggest that the kinetic behavior of Ni compounds administered orally is closely related with the solubility of Ni compounds, and that the solubility of Ni compounds is one of the important factors for determining the health effect of Ni compounds.

Absorption↗

Combination effects of clastogens in the mouse peripheral blood micronucleus assay.

In order to study how two chemicals interact to induce micronuclei, simple ethylating agents [ethyl methanesulfonate (EMS), ethyl ethanesulfonate (EES) and N-ethyl-N-nitrosourea (ENU)], spindle poisons [vincristine sulfate (VINC) and colchicine (COL)] and an oxidizing agent [potassium bromate (KBrO3)] were used as model chemicals for combination treatments. The frequency of micronucleated reticulocytes (MNRETs) was evaluated in mice treated with two of these chemicals at a time. The combinations of ethylating agents (EMS and EES; EMS and ENU) and of spindle poisons (VINC and COL) induced more micronuclei than those expected on an additive basis. The apparent synergism was due to a 'combined dose' which could be calculated by the dosimetric conversion of one chemical to the other, when damage induced by each chemical was 'equivalent' in the induction of MNRETs. In contrast, no apparent synergism in induction of micronuclei was observed when two chemicals with different modes of clastogenic action (EMS and KBrO3 or EMS and VINC) were combined.

Alkylating Agents↗

Sensitivity and specificity of mass screening for gastric cancer using the measurment of serum pepsinogens.

The aim of this study was to estimate the validity of mass screening for gastric cancer using serum pepsinogens (PG test). The study subjects were 4876 workers aged from 40 to 61 years old. Sera were obtained at the time of the health checkup and serum pepsinogen levels (PG I and PG II) were measured at the same time. PG I < 50 ng/ml and PG I/PG II ratio < 3.0 were adopted as the criteria for a positive result for the PG test. PG test-positive subjects were examined, in principle, by endoscopy. Furthermore, all subjects were followed up for a year to check for occurrence of gastric cancer. Among the total subjects, 911 (18.7%) were positive for the PG test and 650 (71.4%) among the positive subjects underwent further examinations, which revealed 11 cases of gastric cancer. Seven gastric cancer cases were diagnosed during the follow-up period within one year after the PG test. When the results of one years's follow-up from the time of screening were defined as the gold standard, the sensitivity and specificity of the PG test were estimated at 66.7% and 81.5%, respectively. The authors conclude that the validity of the PG test as a mass screening method may be comparable to that of X-ray screening, if optimum criteria of a positive test are selected.

Adult↗

Choroid plexus carcinoma in the lateral ventricle--case report.

A 68-year-old male presented with choroid plexus carcinoma in the left lateral ventricle manifesting as dysarthria and gait disturbance. Magnetic resonance imaging showed a homogeneously enhanced mass in the trigone of the left lateral ventricle. Selective left posterior cerebral arteriography showed the tumor was fed by the left medial posterior choroidal artery. Detailed examinations found no evidence of an extraneural primary focus. He underwent partial removal of the tumor followed by local Lineac irradiation (50 Gy). After irradiation, the serum level of carcinoembryonic antigen decreased and the size of the residual tumor was reduced.

Adenocarcinoma↗

[Severe hyperbilirubinemia after cisplatin-based chemotherapy].

Cisplatin is the most effective and widely used anti-cancer drug for ovarian cancer. We report 2 cases with severe hyperbilirubinemia after cisplatin-based chemotherapy. Case 1 was a 67-year-old woman with stage IV ovarian cancer. After operation, she had 2 courses of chemotherapy consisting of cisplatin (90 mg) and cyclophosphamide (550 mg). The regimen was changed to low-dose consecutive cisplatin (10 mg/day, day 1-day 5) because of her ileus and poor performance status. After 2 courses of cisplatin alone, her total bilirubin was elevated to 19.1 mg/dl. She died of respiratory distress. At autopsy, chronic cholangiolitis with intrahepatic bile stasis were noted. Case 2 was a 60-year-old woman with stage IIIc ovarian cancer. After operation she was treated with carboplatin (383 mg/day, day 1) and cisplatin (102 mg/day, day 3). One month after completing the first chemotherapy, her bilirubin elevated to 20.5 mg/dl. It took 3 months to normalize the serum bilirubin with steroid administration. During the second course using the same regimen as in the first course, the bilirubin elevated again. Cisplatin was suspected to be the drug inducing her hyperbilirubinemia. She was consecutively treated with carboplatin alone and the bilirubin did not elevate. Both cases had blood transfusion and intravenous hyperalimentation. It is difficult to disregard the effect of other drugs and therapy. In case 2, her bilirubin elevated repeatedly after cisplatin administration. Cisplatin may thus be the drug which induces the liver dysfunction.

Aged↗