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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

[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↗
PubMed1995

[A case of dural arteriovenous malformation in the anterior fossa associated with an occlusion of the unilateral middle cerebral artery with moyamoya phenomenon].

The authors report a case of dural arteriovenous malformation (dAVM) in the anterior fossa that was associated with an occlusion of the unilateral middle cerebral artery with Moyamoya phenomenon. The patient was a 79-year-old man referred to our department with an episode of consciousness disturbance and headache. Computed tomography scan showed intracerebral hematoma in the left frontal lobe, combined with left frontal subdural hematoma and subarachnoid hemorrhage. Angiography revealed dAVM in the left anterior fossa, fed by the bilateral ethmoidal and the bilateral middle meningeal arteries, and draining into the superior and inferior sinuses through the pial veins with vascular sacs. While angiography revealed an occlusion of the right middle cerebral artery (M1 portion) good collaterals via leptomeningeal anastomosis had developed. T1-weighted magnetic resonance (MR) images showed an intracerebral hematoma as a low intensity area, and flow-void areas were indicative of vascular sacs. Time-of-flight MR angiography also clearly showed dAVM in the left anterior fossa. Co-existence of an occlusion of an intracranial major artery and dAVM in this location has not been reported previously and it was speculated that this association had occurred by chance.

Aged↗
PubMed1995

[Evaluation of myocardial ischemia using Holter monitoring].

To establish the diagnostic criteria for myocardial ischemia, Holter monitoring and coronary angiography were performed on 46 cases (24 males (51.8 +/- 9.3 years), 22 females (47.5 +/- 10.5 years)). These patients were retrospectively selected from about 12000 patients who had the Holter monitorings from 1980 to 1993. The criteria for the entry were 1) reliable trend recordings of heart rate and 2) reliable recording of ST trend with accurate 1 mV calibration. The coronary stenosis greater than 75% in diameter was considered to be significant. Results were as follows: 1) ST trend pattern was classified into typical type, atypical type and box type. There were no significant differences in the incidence of typical and atypical types between ischemic and nonischemic groups, 2) Diagnostic accuracy of the criteria for myocardial ischemia, that is, the horizontal or downsloping ST segment depression with 0.1 mV at the point of 80 msec from the J point lasting for 1 minute, was higher in male than in female: the sensitivity was 93.3% and the specificity was 55.6% for men respectively, whereas the sensitivity was 66.7% and the specificity was 37.5% for women respectively, 3) Diagnostic accuracy of the ST/Heart rate ratio was 80.0% for the sensitivity and 64.7% for the specificity, indicating an improvement of specificity, 4) Maximal ST segment depression was accompanied by pain by 88.8% in true positive group (significant ST segment depression with significant coronary stenosis), whereas that was 28.6% in false positive group (significant ST segment depression without significant coronary stenosis), 5) Comparison of the degree of maximal ST segment depression, duration and frequency between computer and manual measurement showed a good correlation for the degree of maximal ST segment depression, whereas the duration and the frequency showed no significant correlations. The above results suggest that combined evaluation of the ST segment depression criteria (downsloping or horizontal ST segment depression greater than 1 mm at the point of 80 msec from the J point) and the ST/Heart rate criteria (1.4 microV/beats/min) is useful for the diagnosis of myocardial ischemia using Holter monitoring.

Adult↗
PubMed1995

Evaluation of binding equation method for prediction of unbound serum valproic acid concentration in pediatric patients with epilepsy.

We retrospectively evaluated the ability of Scatchard binding equation method to predict the unbound serum valproic acid (VPA) concentration in 37 pediatric patients with epilepsy receiving VPA monotherapy. The correlation between predicted and observed unbound serum concentrations was high and significant (r = 0.873, p < 0.001). Mean prediction error (ME), mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated, and served as a measure of prediction bias and precision. The 95% confidence intervals of ME did not include 0, showing a bias to overpredict unbound concentration. The MAE and RMSE were not small in magnitude (MAE 17.4 mumol/l, RMSE 22.8 mumol/l). The current method using the in vivo population mean binding parameters from healthy young adults may be limited in the predictive performance of unbound serum VPA concentration.

Adolescent↗
PubMed1994

Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity.

In an effort to clarify the regulation of distribution and actions of transforming growth factor (TGF)-beta in bone, TGF-beta 1 binding to extracted bone matrix proteins and the influence of such binding on TGF-beta 1 actions were examined. In-gel binding of 125I-TGF-beta 1 using extracts from mineralized bovine bone matrix demonstrated that 125I-TGF-beta 1 was almost exclusively bound to a proteoglycan, decorin. The binding was via the core protein of decorin. Scatchard analysis of the binding of 125I-TGF-beta 1 to immobilized decorin purified from osteoblastic MC3T3-E1 cell conditioned medium revealed that there were two specific binding sites with high and low affinities for TGF-beta 1 (Kd = 0.3 and 5 nM, respectively). The addition of decorin along with TGF-beta 1 enhanced the inhibitory effect of TGF-beta 1 on MC3T3-E1 cell proliferation. Decorin in itself did not affect their proliferation. These cells possessed types I and II TGF-beta receptors and betaglycan, and the addition of decorin increased the binding of 125I-TGF-beta 1 to all these receptors. These results demonstrate that the core protein of decorin specifically binds TGF-beta 1 with high affinities and that the binding of TGF-beta 1 to decorin increases TGF-beta 1 binding to its receptors and enhances its bioactivity. Because TGF-beta is released by bone resorption along with matrix proteins, including decorin, and because it stimulates the synthesis of these proteins, it is suggested that the binding and enhancement of the activities of TGF-beta by decorin may play a role in maintaining bone formation during bone remodeling process.

3T3 Cells↗
PubMed1994

Frequent involvement of visible chromosomal deletion in X-ray-induced mutants at the HLA-A locus in human T-lymphocytes.

Mutant T-lymphocytes at the HLA-A locus were isolated using a recently developed flow-cytometric assay either immediately after drawing blood (in vivo mutants) or after X-irradiation in vitro. Mutants were subsequently propagated clonally for cytogenetic and molecular analyses. Among the 38 in vivo mutants, none contained an abnormal chromosome 6 on which the HLA-A locus resides (6p21.3). In contrast, mutants recovered after in vitro irradiation frequently carried abnormalities in the short arm of chromosome 6: 11/19 and 5/5 independent mutants for the 1-Gy and 2-Gy groups, respectively. Characteristically, the majority of the aberrations were deletions, commonly involving chromosome 6p21-p23. Because chromosomal deletions involving the selected gene are rare among radiation-induced mutants at the hypoxanthine phosphoribosyltransferase (chromosome X) and thymidine kinase (chromosome 17) loci, the HLA-A locus can be considered as highly prone to chromosomal deletions after radiation exposure. It is generally believed that ionizing radiation randomly breaks DNA, and the higher frequency of chromosomal deletions at the HLA-A locus is unlikely to be due to preferential induction but more likely to the better survivability of the deletion-bearing mutants. Consequently, the results suggest that the human genome is quite heterogeneous with regard to the survivability of cells bearing a chromosomal deletion including different loci.

Cells, Cultured↗
PubMed1994

In vitro chemosensitivity test of human brain tumors using a three-dimensional organ culture with a collagen gel matrix.

We evaluated the usefulness of an in vitro tumor organ culture system using a specialized collagen gel matrix derived from pig skin as a chemosensitivity test for human brain tumors. Two xenograft tumors derived from human glioblastoma and medulloblastoma were examined with this system and the results were compared with data obtained from a nude mouse assay. Xenograft tumors exhibited in vivo-like three-dimensional growth on the collagen gel matrix and had increasing incorporation of tritiated (3H)thymidine for 2 weeks. Drug sensitivity, as measured by this assay at therapeutic peak plasma concentrations of anticancer drugs, corresponded with that measured with the nude mouse assay. Chemosensitivity of 16 surgical specimens of malignant brain tumors were also examined successfully by this collagen gel matrix (CGM) assay. When the highest inhibition rate in dose-inhibition curve was equal to or greater than 50%, the tumor was regarded to be sensitive to the agent. The efficacy rates in CGM assay for 16 lesions were 25.0% (4/16) for ACNU, 67.8% (11/16) for adriamycin, 31.3% (5/16) for cisplatin, and 67.8% (11/16) for etoposide. The CGM assay has advantages as a chemosensitivity test because of its simple procedure, rapidity, high rate of evaluable tumor growth, and in vivo-like three dimensional tumor growth. Our results indicate that the CGM assay is feasible to test the chemosensitivity of malignant brain tumors.

Animals↗
PubMed1994

Pulmonary elimination of methyl tertiary-butyl ether after intraperitoneal administration in mice.

The pulmonary elimination after intraperitoneal administration at three different doses (50, 100, and 500 mg/kg) of methyl tertiary-butyl ether (MTBE) was studied using mice. There were two exponential curves with an initial rapid decrease of the elimination ratio followed by a slow decrease at the doses of 100 mg/kg and 500 mg/kg. The calculated half-lives of the two elimination curves obtained by the least squares method were approximately 45 min and 80 min. The pulmonary elimination ratios at the three different doses were from 23.2% to 69.0%. Most of the excreted MTBE was eliminated within 3 h. It is suggested in this paper that MTBE in exhaled air can be used as a biological exposure index for the exposure assessment of MTBE.

Animals↗