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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 163 records · Page 9Linked to original sources

[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↗

[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↗

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↗

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↗

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↗

Aryl hydrocarbon hydroxylase activity in human lung tissue: in relation to cigarette smoking and lung cancer.

In order to investigate the relationship between aryl hydrocarbon hydroxylase (AHH) activity and smoking or lung cancer, AHH activities in fresh lungs (normal tissue, tumorous tissue, and surrounding tissue of tumor) obtained from lung cancer patients and non-lung cancer patients were measured. There were no differences in lung AHH activity in the lung lobes. In the non-lung cancer patients, AHH activities ranged from 0.13 to 2.37 (pmol 3 hydroxybenzo[a]pyrene/20 min/mg protein), and whereas in the normal tissues of the lung cancer patients they ranged from 0.19 to 5.05. Lung AHH activities showed normal distribution, and a large variation (26 times) was observed in normal tissues in the lung cancer patients. In most cases, AHH activities in the tumorous tissues and the surrounding tissue of the tumor were lower than those in the normal tissues of the lung cancer patients. In the non-lung cancer group, the means of AHH activity of the nonsmoker subgroup (NN) and the smoker subgroup (SN) were 0.62 and 0.96, respectively. On the other hand, in the lung cancer group the means of AHH activity of the nonsmoker subgroup (NC) and smoker subgroup (SC) were 0.85 and 1.05, respectively. Statistically significant differences were observed between NN and SN, NN and NC, and NN and SC. These results suggest that human lung AHH activity was increased by cigarette smoke as in rodent lungs, and the distribution of basal AHH activity in lung tissue of the nonsmokers group in the lung cancer patients shifted toward high levels compared to the nonsmokers group in the non-lung cancer group. The effect of the histological cell types of the lung cancer on the AHH activity was not observed in this study.

Adenocarcinoma↗

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↗

Efficiency of serum copper/zinc ratio for differential diagnosis of patients with and without lung cancer.

We examined serum copper (Cu), serum zinc (Zn), and the serum copper/zinc ratio (Cu/Zn) in 162 patients. All of them were seen to have an abnormal shadow in the chest X-ray films, that is, 109 patients with lung cancer (LC) and 53 patients with no lung cancer (NLC). The mean Cu and Cu/Zn in LC patients were significantly higher than those in NLC patients (p < 0.05). In LC patients, Cu and Cu/Zn were higher and Zn was lower in advanced tumors than early ones. There was a significantly clear relation between Cu or Cu/Zn and the tumor (T) stages. When the relative risk (RR) of LC was estimated, it was seen that the higher Cu and Cu/Zn became, the higher RR became. Furthermore, we showed the sensitivity of the receiver operator characteristic of the test (ROC) curve for Cu, Cu/Zn, and carcinoembryonic antigen (CEA) to diagnose LC, as explained in a paragraph of methods. The determinations of Cu, Zn, and Cu/Zn are simple and inexpensive. They also appear to have a great diagnostic value in determining the local invasion of LC and as a screening test in the high-risk patients for LC.

Adult↗

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↗

Aneuploidy in somatic cells of in utero exposed A-bomb survivors in Hiroshima.

Cytogenetic data on cultured lymphocytes of the in utero exposed A-bomb survivors in the RERF Adult Health Study cohort have been analyzed using the G-banding technique to determine the frequency of aneuploid cells. The data consist of blood samples collected between 1985 and 1987 from 264 Hiroshima individuals for whom DS86 maternal uterine dose estimates are available: 124 proximally exposed (74 males and 50 females) with an estimated dose of 0.005 Sv or more, and 140 distally exposed (76 males and 64 females) with a dose estimate of 0 Sv, assuming the neutron relative biological effectiveness (RBE) of 10. A main feature of aneuploidy was that aneuploid frequency in autosomes depended generally on chromosome length; aneuploidies were significantly more frequent in shorter chromosomes than in longer chromosomes. The frequency of aneuploidies also depended on type, with chromosome loss approximately five times more frequent than chromosome gain. However, chromosome 21, as well as the sex chromosomes, were notable in that aneuploidy was much more frequent for these chromosomes than would be predicted from a simple relationship with length. X chromosome aneuploidies were significantly more frequent in females than in males. There was no dependence of aneuploid frequencies on dose when measured 40 years after the exposure.

Adult↗

Passive immunisation against experimental salmonellosis in mice by orally administered hen egg-yolk antibodies specific for 14-kDa fimbriae of Salmonella enteritidis.

Chickens were immunised with a preparation of purified 14-kDa fimbriae of Salmonella serotype Enteritidis (SEF 14) to raise egg-yolk antibodies for protection trials in mice against subsequent challenge-exposure with the homologous strain of Enteritidis. A pronounced specificity of egg-yolk antibodies against the 14-kDa fimbrial antigen was demonstrated by Western blotting analysis. Passive antibody protection was evaluated in a mouse model of experimental salmonellosis: 79 mice (CD 1 strain) were challenged orally with 2 x 10(10) cfu of Enteritidis. Test mice treated with SEF-14 antibodies (titre = 128) had a survival rate of 77.8% compared to 32% survival in control mice fed normal egg-yolk antibodies (titre < 10) (p < 0.01). In-vitro adhesion of Enteritidis to mouse intestinal epithelial cells was reduced by anti-fimbrial antibodies. An indirect immunofluorescence method demonstrated the localisation of Enteritidis along the villous margins of the small intestine of control mice, whereas in test mice adherent bacteria were not detected. Results suggest that 14-kDa fimbriae may influence, enhance or contribute to the overall adhesive properties of Enteritidis and that egg-yolk antibodies directed against these fimbriae may have played a substantial role in protection, possibly by minimising bacterial colonisation and invasion during the early stages of infection.

Administration, Oral↗

Distribution of urinary hippuric acid concentrations by ALDH2 genotype.

OBJECTIVES: To clarify the relation between the genetic polymorphism of ALDH2 (low Km aldehyde dehydrogenase) and toluene metabolism. METHODS: The study subjects were 253 toluene workers (192 men and 61 women with an age range of 18-66). The genotypes of ALDH2 were classified by artificial restriction fragment length polymorphism into the homozygous genotype of normal ALDH2 (NN), the homozygous genotype of an inactive ALDH2 (DD), and the heterozygous genotype of normal and inactive ALDH2 (ND). The concentrations of hippuric acid (HA), the main metabolite of toluene, was determined in urine specimens of 253 toluene workers. The HA measurements in previous occupational health examinations were also referenced. The HA concentrations corrected for creatinine (HA/C) were compared with the biological exposure index (BEI) for toluene, which is 2.5 g/g creatinine. To estimate the toluene exposures, urinary o-cresol concentrations were also determined and compared with another BEI for toluene--that is, 1.0 mg urinary o-cresol/g creatinine. RESULTS: Incidence of each genotype in the toluene workers was almost the same as that in non-exposed controls who lived in the same area as the toluene workers. The incidence of each of the three genotypes also did not differ by smoking habit. Mean urinary HA concentrations were not significantly different in the groups with the different genotypes of ALDH2. The HA concentrations of > 70% of the 890 total samples were < 1.0 g/l. The number of urine samples > 3.0 g/l was 28 (5.4%) in the NN group and 19 (6.4%) in the ND group. No urine samples in the DD group were > 3.0 g/l HA. The distribution of urinary HA in the DD group was significantly different from those in both the NN and ND groups (P < 0.05). Seven (4.9%) of the 136 total specimens in the NN group and four (4.7%) of the 82 total specimens in the ND group exceeded the BEI. There were, however, no urine specimens that exceeded the BEI in the DD group. The maximum HA concentration after correction for creatinine in the DD group was 1.86 g/g creatinine. The percentages of urine specimens in which o-cresol concentrations exceeded this BEI were 14.3% in the NN group, 9.1% in the ND group, and 15.4% in the DD group. Therefore, the exposure rate for all three genotypic groups of workers was almost the same. CONCLUSIONS: The HA concentrations of toluene workers with ALDH2 DD genotype were lower than those of the NN and ND genotypes when they were exposed to relatively high concentrations of toluene. The exposures of the DD group were suspected to be underestimates because they were based on the BEI for the NN genotype.

Adolescent↗

Confirmation study, using nitrobenzene, of the Combined Repeat Dose and Reproductive/Developmental Toxicity Test protocol proposed by the Organization for Economic Cooperation and Development (OECD).

A confirmatory familiarization study of the Combined Repeat Dose and Reproductive/Developmental Toxicity Screening (ReproTox) test protocol proposed by the Organization for Economic Cooperation and Development (OECD) was performed using nitrobenzene, a testicular toxicant. The agent was given daily by gavage to groups of 10 male and 10 female Sprague-Dawley rats at doses of 100, 60, 20 and 0 mg/kg body weight. Some of the high dose animals exhibited neurological signs, and two males and 9 females died. Hemolytic anemia due to methemoglobin formation was evident in treated males. Histopathologically, treated males showed atrophy of seminiferous tubules of the testis, reactive changes secondary to hemolytic anemia in the hematopoietic organs, and hepatocellular swelling. Cerebral gliosis was observed in middle and high dose males. Male fertility was not affected. The body weights of pups from treated dams were lowered, and their postnatal loss was increased. Most of the known toxicological properties of this chemical was demonstrated in the present study, with the exception of reduced fertility. Therefore, the ReproTox protocol was concluded as being useful as a screening test of existing high production volume chemicals. It should be noted that while the reproductive toxicity test alone is insensitive for detection of male fertility disturbances associated with testicular toxicity, the latter easily be distinguished on morphological grounds.

Animals↗