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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intramedullary schwannoma of the spinal cord: report of two cases.

We report magnetic resonance findings in the intramedullary schwannoma of the cervical spinal cord in two patients. In both cases, the solid portions of the tumours enhanced intensely after administration of Gd-DTPA and the enhanced border was sharply delineated from the adjacent spinal cord. Schwannomas should be considered in the differential diagnosis of intramedullary tumours when magnetic resonance images show a strongly enhancing mass with sharply delineated borders.

Adolescent↗
PubMed2001

Transgene expression of thioredoxin (TRX/ADF) protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hematotoxicity.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has a variety of toxic effects on a number of organs, including the hematopoietic system. The importance of TCDD-induced oxidative stress has been evaluated in several target organs. However, its role in hematotoxicity remains poorly understood, although bone marrow is known to produce reactive oxygen species. The aim of this study is to evaluate not only the contribution of oxidative stress to TCDD-induced hematotoxicity but also the protective function of TRX/ADF, a known anti-oxidative stress agent, on the hematotoxicity of TCDD in ADF wild-type (WT) and transgenic (Tg) mice. WT and Tg mice received a single intraperitoneal injection of 20 microg TCDD/kg. One day after the treatment, blood and bone marrow cellularity was measured and bone marrow levels of granulotyce/macrophage colony-forming units were determined in the in vitro colony assay. The expression of human TRX transgene by their bone marrow cells was analyzed by Western blot electrophoresis. Our results showed that overexpression of TRX/ADF protects against TCDD-induced hematotoxicity, indicating that induction of oxidative stress that results in disruption of redox regulation may be an important mechanism in TCDD-induced bone marrow toxicity. Moreover, we detected a significant decrease of AhR mRNA levels in bone marrow cells of Tg mice following TCDD treatment, suggesting a biological role of TRX/ADF in the AhR-mediated pathway through which TCDD induces oxidative stress.

Animals↗
PubMed2001

Butylhydroxytoluene (BHT) increases susceptibility of transgenic rasH2 mice to lung carcinogenesis.

PURPOSE: Transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) are highly susceptible to lung carcinogens. In order to investigate the possibility of developing a rapid in vivo assay for lung carcinogens, we examined whether the tumor-promoting activity of butylhydroxytoluene (BHT) is efficacious in rasH2 mice. METHODS: rasH2 mice and wild littermates of both genders were pre-treated with carcinogens [urethane (UR), 4-nitroquinoline 1-oxide (4NQO) or diethylnitrosamine (DEN)], and, one day later, given a 400 mg/kg dose of BHT. RESULTS: Six weeks after the initiation treatment, evidence of carcinogenicity could be detected in male and female rasH2 mice that had received UR doses of > or = 250 mg/kg and > or = 125 mg/kg, respectively, prior to exposure to BHT, whereas only 500 mg/kg of UR was sufficient to induce tumors in female rasH2 mice given the carcinogen alone. The carcinogenicity of 15 mg/kg of 4NQO could be detected after 9 weeks in male rasH2 mice given the carcinogen followed by BHT. Similarly, the carcinogenicity of 60 mg/kg of DEN could be detected after 9 weeks and 6 weeks, respectively, in male and female rasH2 mice given the carcinogen followed by BHT. No carcinogenicity could be demonstrated through the experimental period with doses of 4NQO or DEN given alone. CONCLUSIONS: These results indicate that BHT administration increases the susceptibility of rasH2 mice to lung carcinogens, and suggest that the use of BHT in rasH2 mice might lead to the establishment of a rapid in vivo assay for lung carcinogens.

Adenocarcinoma↗
PubMed2001

Design and evaluation of PCR primers to amplify bacterial 16S ribosomal DNA fragments used for community fingerprinting.

Denaturing gradient gel electrophoresis of PCR-amplified 16S ribosomal DNA (rDNA) fragments has frequently been applied to the fingerprinting of natural bacterial populations (PCR/DGGE). In this study, sequences of bacterial universal primers frequently used in PCR/DGGE were compared with 16S rDNA sequences that represent recently proposed divisions in the domain Bacteria. We found mismatches in 16S rDNA sequences from some groups of bacteria. Inosine residues were then introduced into the bacterial universal primers to reduce amplification biases caused by these mismatches. Using the improved primers, phylotypes affiliated with Verrucomicrobia and candidate division OP11, were detected in DGGE fingerprints of groundwater populations, which have not been detected by PCR/DGGE with conventional universal primers.

Bacteria↗
PubMed2001

Mechanism of action of benzene toxicity: cell cycle suppression in hemopoietic progenitor cells (CFU-GM).

The aim of this study was to clarify previously reported controversial data and hypotheses concerning the effect of benzene on the cell cycle of hemopoietic stem cells. In this study, the bromodeoxyuridine UV (BUUV) suicide assay was performed in normal C57BL/6 and p53 knockout (KO) C57BL/6 mice during and after exposure to 300 ppm of benzene for 2 weeks. Our kinetic studies revealed that the cell cycle of hemopoietic myeloid progenitor cells (colony-forming unit granulocyte-macrophage [CFU-GM]), rather than being stimulated, was suppressed by exposure to benzene. The fraction of CFU-GM in S phase was significantly depressed, from 37.1% in controls to 16.3% in normal mice. BrdUrd incorporation in both groups revealed significantly different slopes for untreated and benzene-exposed normal C57BL/6 mice. p53 appeared to induce suppression of both the number and the cycling fraction of hemopoietic progenitor cells, as demonstrated by the lack of benzene-induced suppression of these parameters in p53 KO mice. The likelihood that suppression of bone marrow cellularity and cell cycling is mediated by p53 was supported by the upregulation of p21, a cyclin-dependent kinase inhibitor. Our present study revealed the mechanism of action of benzene hematotoxicity. Benzene suppresses the cell cycle by p53-mediated overexpression of p21, a cyclin-dependent kinase inhibitor, resulting not simply in suppression of hemopoiesis but rather in a dynamic change of hemopoiesis during and after benzene exposure. Thus, the controversies raised by previously reported data are resolved by our present findings of hemopoietic stem cell kinetics.

Animals↗
PubMed2001

Gender- or age-related binding characteristics of valproic acid to serum proteins in adult patients with epilepsy.

The aim of the present study was to determine the gender- or age-related binding characteristics of valproic acid (VPA) to serum proteins in the adult population. Serum samples examined in the study were obtained from 70 adult patients (36 males, 34 females) with epilepsy on VPA monotherapy. Their age ranged from 16 to 68 years (mean age with (SD), 37.7 (15.7) years; <45 years, n=44; >/=45 years, n=26). The in vivo population binding parameters of VPA to serum proteins and theoretical minimal unbound serum VPA fraction (Fu) were determined using an equation derived from the Scatchard equation in: (1), all; (2), male and female subgroups; and (3), younger (<45 years) and older (>/=45 years) subgroups. There was a significant difference in serum concentration of unbound VPA between male and female patients. The mean association constant (K) was 0.010 microM(-1) in all, male, and female patients. The mean total concentration of binding sites (n(Pt)) was 1453 microM for all patients, and 1561 and 1394 microM for male and female patients, respectively. The Fu was 0.064 for all patients, and 0.060 and 0.067 for male and female patients, respectively. There were no significant differences in the binding characteristics of VPA to serum proteins between the male and female groups. On the other hand, there were significant differences in the serum albumin concentration and molar concentration ratio of free fatty acids to albumin in serum between the younger and older patients. The mean value of K was 0.016 microM(-1) for the younger patients and 0.007 microM (-1) for the older patients. The mean n(Pt) was 1157 microM for the younger patients and 1703 microM for the older patients. The Fu was 0.051 for the younger patients and 0.077 for the older patients. Thus, significant differences were observed in the binding characteristics of VPA to serum proteins between the younger and older groups. Our results show that age, but not gender, has significant influences on the binding characteristics of VPA to serum proteins in our patient population.

Adolescent↗
PubMed2001

Analysis of portal venous waveform after living-related liver transplantation with pulsed Doppler ultrasound.

We evaluate the portal venous waveform (PVW) with pulsed Doppler ultrasound (US) after living-related liver transplantation (LRLT) and correlate it with subsequent abnormalities. In the first 2 wk after LRLT, pulsed Doppler US demonstrated three types of PV waveform (PVW) in 33 recipients: non-phasic PVW in 19 patients, pulsatile in 10, and turbulent in 4. In the pulsatile PVW group, arterio-portal (A-P) shunt was confirmed in three grafts by either arteriograhy or computed tomography during hepatic arteriography. A severe stenosis in the grafted vein was confirmed in one case by both US and venography. The pulsatile PVW in the remaining six cases spontaneously disappeared and turned to the non-phasic PVW without treatment. The graft volume/liver standard volume (GV/SV) ratio was significantly smaller in the pulsatile PV waveform group than in the non-phasic PVW group (p<0.01). In the turbulent PVW group, aneurysmal-like dilatation of the portal vein at the umbilical portion was formed in 3 of the 4 patients. The pulsatile waveform in the PV is frequently observed with pulsed Doppler after LRLT, especially in patients that received small grafts. We should keep in mind that they often disappear without any treatment, although some examples of pulsatile waveforms represent vascular complications.

Adolescent↗
PubMed2001

Effect of temperature on serum protein binding characteristics of phenytoin in monotherapy paediatric patients with epilepsy.

OBJECTIVES: To determine the effects of temperature on binding characteristics of phenytoin to serum proteins in paediatric patients with epilepsy. METHOD: Serum samples examined in the study were obtained from 41 paediatric patients (23 male, 18 female) with epilepsy on phenytoin monotherapy. Their age ranged from 1 to 15 years (mean +/- SD, 10;2 +/- 4;0 years). Protein binding of phenytoin was evaluated by ultrafiltration under current laboratory routine conditions (25 +/- 3 degrees C) or at a temperature of 37 degrees C. The in vivo binding parameters of phenytoin to serum proteins were determined using a binding equation derived from the Scatchard equation for a one-site binding model. RESULTS: Significant differences were observed in serum concentrations of unbound phenytoin at the two temperatures (P < 0;05). The mean association constant L/micromol (K) of phenytoin to serum proteins is 0.016 L/micromol at 25 +/- 3 degrees C and 0;009 L/micromol at 37 degrees C, while mean total concentration of binding sites (n(Pt)) seems to be similar between the two temperatures (682 micromol/L for 25 +/- 3 degrees C and 746 micromol/L for 37 degrees C). Significant differences were observed in binding characteristics of phenytoin to serum proteins for the different temperature conditions of ultrafiltration (P < 0;05). CONCLUSION: Our study confirms that binding affinity for phenytoin-serum protein interaction is approximately 44% lower at 37 degrees C than at 25 +/- 3 degrees C and consequently, binding potential (K.n(Pt)) is approximately 38% lower at 37 degrees C than at 25 +/- 3 degrees C.

Adolescent↗
PubMed2001

Longitudinal follow-up study of 11 patients with pulmonary lymphangioleiomyomatosis: diverse clinical courses of LAM allow some patients to be treated without anti-hormone therapy.

OBJECTIVE: The purpose of this study is to clarify the existing issues on the clinical diversity, natural history, and mode of disease progression of pulmonary lymphangioleiomyomatosis (LAM). METHODOLOGY: Eleven patients with LAM were reviewed retrospectively with special reference to serial changes in pulmonary function and radiological findings during the course of their disease, treatment, and outcome. All patients were female with a mean age of 33.8 years at presentation and the observation period ranged from 2.1 to 20.8 years (mean 7.4 years). RESULTS: Four of six patients, treated with anti-hormone therapy, presented with exertional dyspnoea, marked airflow limitation (forced expiratory volume in 1 s/forced vital capacity, 23-38%), and severely impaired diffusing capacity (%DLCO, 21.4-36% of the predicted). The remaining two patients showed only a decreased diffusing capacity (70.6% and 59.4% of the predicted) which rapidly deteriorated with subsequent development of airflow limitation. Repeated chest computed tomographic (CT) examinations revealed increasing numbers of cysts with simultaneous loss of normal lung parenchyma in these two patients. In contrast, the five patients who received no anti-hormone therapy had no respiratory symptoms aside from pneumothorax at onset. Remarkable differences were noted, with pulmonary function being well maintained and slow progression of cystic changes on CT being observed in the latter group. CONCLUSIONS: Diverse clinical courses observed in patients with pulmonary LAM can be well delineated and assessed by periodic examinations including pulmonary function tests and chest CT imaging. Anti-hormone therapy is not always necessary for a certain group of LAM patients and they appear to have a stable course and favourable outcomes without anti-hormone treatment.

Adult↗
PubMed2001

Infection of replication-deficient adenoviral vector enhances interleukin-8 production in small airway epithelial cells more than in large airway epithelial cells.

OBJECTIVE: In clinical trials or experiments of gene therapy, airway administration of an adenoviral-based vector (E1A-deleted) elicits a dose-dependent inflammatory response with limitation in the duration of transgene expression. The purpose of this study was to evaluate the possibility that the adenoviral-based vector directly enhances IL-8 production independent of adenoviral E1A in normal human airway epithelial cells and to examine the different responses between primary human bronchial epithelial cells (HBE) and primary human small airway epithelial cells (HSAE) in production of IL-8 following exposure to an adenovirus vector. METHODOLOGY: Interleukin (IL)-8 levels were evaluated in the culture medium from HBE and HSAE treated with increasing doses of E1A-deleted adenoviral vector contained the Escherichia coli LacZ reporter gene (AdCMVLacZ). To clarify the mechanism of enhancing IL-8 production in airway epithelial cells by infection with adenovirus vector, alphavbeta5 agonistic antibody as an analogue of adenoviral capsid and adenoviral capsid vector denatured by exposure to ultraviolet (UV) light were used in the present study. RESULTS: Inoculation of HBE with AdCMVLacZ at a multiplicity of infection (MOI) of between 1 and 200 resulted in a dose-dependent expression of LacZ, and maximal expression was observed at a MOI of 100. In contrast, inoculation of HSAE with AdCMVLacZ resulted in maximum expression of LacZ at a MOI of 10. Interleukin-8 levels in culture media from the same experiments revealed significantly greater production of IL-8 in HSAE inoculated with AdCMVLacZ at a MOI of 50, compared to HBE under the same conditions. The capsid-denatured adenoviral vector did not enhance IL-8 production, and alphavbeta5 agonistic antibody induced IL-8 enhancement. CONCLUSION: These results suggest that the adenoviral vector directly induces the expression of airway epithelial inflammatory cytokines in the pathogenesis of inflammation and that small airway cells have a greater affinity for adenovirus than other airway epithelial cells.

Adenoviruses, Human↗
PubMed2001

The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activities in humans.

OBJECTIVE: Our objective was to evaluate the activity of cytochrome P4501A2 (CYP1A2), xanthine oxidase (XO), and N-acetyltransferase 2 (NAT2) from early to late pregnancy and after delivery. METHODS: Twelve women were studied on three occasions during pregnancy (early, 8-16 weeks' gestation; middle, 20-28 weeks' gestation; and late, 32-39 weeks' gestation) and about 1 month after delivery. Caffeine was used as a metabolic probe. After the women ingested a can or a bottle of caffeine-containing soft drink, urine samples were collected for 12 hours. The caffeine metabolites measured were 5-acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1X), 1-methyl-uric acid (1U), 1,7-dimethyl-uric acid (17U), and 1,7-dimethylxanthine (17X). The hepatic enzyme activities were estimated by the urinary caffeine metabolic ratios as follows: CYP1A2 = (AAMU + 1X + 1U)/17U; XO = 1U/(1X + 1U); NAT2 = AAMU/(AAMU + 1X + 1U). RESULTS: Statistically significant differences were found in CYP1A2 (P < .0001) and NAT2 (P < .01). The mean metabolic ratios for CYP1A2 during pregnancy (6.80, 5.18, and 4.97 for the early phase, middle phase, and late phase, respectively) were significantly lower than the ratio after delivery (10.39). The mean metabolic ratio for NAT2 in the early phase (0.57) was significantly lower than after delivery (0.66). There was no significant difference in metabolic ratios for XO during pregnancy and after delivery. CONCLUSION: The data demonstrate that pregnancy influences CYP1A2 and NAT2 activity. CYP1A2 activity decreases not only in late pregnancy but also in early and middle pregnancy.

Adult↗
PubMed2001

Detection of stable chromosome aberrations by FISH in A-bomb survivors: comparison with previous solid Giemsa staining data on the same 230 individuals.

PURPOSE: To evaluate the relative abilities of the solid Giemsa staining (conventional) and fluorescence in situ hybridization (FISH) methods in the detection of stable chromosome aberrations in the peripheral blood lymphocytes of A-bomb survivors. MATERIALS AND METHODS: Lymphocytes from a total of 230 A-bomb survivors for whom prior chromosome aberration data had been obtained by the conventional method were recently examined afresh using FISH in which chromosomes 1, 2 and 4 were painted with composite probes. RESULTS: It was found that the early use of the solid Giemsa staining method had allowed the detection of translocations with a mean frequency of 73% of the value for the genome-equivalent translocation frequency (F(G)) that was now obtained using FISH. The disparity may at least in part be due to the reciprocal exchange of seemingly identical amount of chromosome material; such exchanges can escape detection by the conventional method but can be readily identified using FISH. CONCLUSION: It has previously been established that the conventional method can detect about 20% of radiation-induced translocations as abnormal monocentric chromosomes. Present results indicate that an additional 50% can be detected if proper karyotyping is conducted and the remaining 30% are not likely to be detected unless FISH or banding methods are used. Thus, solid Giemsa staining accompanied by karyotyping may not be quite as unsuitable as is generally assumed for retrospective biodosimetry analyses, which deal mainly with stable aberrations.

Azure Stains↗
PubMed2001

FISH examination of lymphocytes from Mayak workers for assessment of translocation induction rate under chronic radiation exposures.

PURPOSE: To estimate the translocation-induction rate under chronic exposure conditions by measuring chromosome aberration frequencies in lymphocytes from Mayak nuclear workers using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: Lymphocytes were examined from 27 nuclear workers at the Mayak Production Association and two control individuals using FISH with probes for chromosomes 1, 2 and 4. Official doses derived from worker film-badge records varied from 0 to 8.50 Gy. RESULTS: The mean (+/-SD) genome-equivalent translocation frequency (F(G)) was 2.30 (+/-0.75)% in the zero-dose group (n = 7), and Poisson regression analysis provided the best-fit equation of F(G)(%) = 2.96(+/-0.39) + 0.69(+/-0.14)D + 0.12(+/-0.05)A, where D is the film-badge-derived dose (Gy), and A is age centred at 67 years. The induction rate would increase to nearly 1% Gy(-1) if the radiation dose to bone marrow, one of the major organs for lymphocytes and where their precursor cells reside, is considered. CONCLUSION: The estimated induction rate in vivo appeared substantially smaller than linear coefficients estimated from various in vitro studies.

Aged↗
PubMed2001

Isolation and characterization of a gene specific to lager brewing yeast that encodes a branched-chain amino acid permease.

We found two types of branched-chain amino acid permease gene (BAP2) in the lager brewing yeast Saccharomyces pastorianus BH-225 and cloned one type of BAP2 gene (Lg-BAP2), which is identical to that of Saccharomyces bayanus (by-BAP2-1). The other BAP2 gene of the lager brewing yeast (cer-BAP2) is very similar to the Saccharomyces cerevisiae BAP2 gene. This result substantiates the notion that lager brewing yeast is a hybrid of S. cerevisiae and S. bayanus. The amino acid sequence homology between S. cerevisiae Bap2p and Lg-Bap2p was 88%. The transcription of Lg-BAP2 was not induced by the addition of leucine to the growth medium, while that of cer-BAP2 was induced. The transcription of Lg-BAP2 was repressed by the presence of ethanol and weak organic acid, while that of cer-BAP2 was not affected by these compounds. Furthermore, Northern analysis during beer fermentation revealed that the transcription of Lg-BAP2 was repressed at the beginning of the fermentation, while cer-BAP2 was highly expressed throughout the fermentation. These results suggest that the transcription of Lg-BAP2 is regulated differently from that of cer-BAP2 in lager brewing yeasts.

Amino Acid Sequence↗
PubMed2001

Chromosome aberration analysis in persons exposed to low-level radiation from the JCO criticality accident in Tokai-mura.

Chromosome aberrations were studied in peripheral blood lymphocytes of 43 persons who were exposed to low-level radiation of mixed neutrons and gamma-rays resulting from the JCO criticality accident. When the age-adjusted frequencies of dicentric and ring chromosomes were compared with the dose calibration curve established in vitro for 60Co gamma-rays as a reference radiation, a significant correlation was observed between the chromosomally estimated doses and the documented doses evaluated by physical means. The regression coefficient of the chromosomal doses against the documented doses, 1.47 +/- 0.33, indicates that the relative biological effectiveness of fission neutrons at low doses is considerably higher than that currently adopted in the radiation protection standard.

Adult↗
PubMed2001

Adsorption effect of activated charcoal on enterohemorrhagic Escherichia coli.

The adsorption property of activated charcoal on verotoxin (VT)-producing Escherichia coli (VTEC) was examined using E. coli O157:H7. In the present study, E. coli O157:H7 strains were effectively adsorbed by activated charcoal. Adsorption was dose-dependent, and the maximum adsorption occurred within 5 min. At 10 mg of activated charcoal, bacteria tested were completely adsorbed. Activated charcoal also had the capacity to adsorb toxin (verotoxin 2) activity from the bacterial extract. Furthermore, the adsorption efficiency of activated charcoal for the normal bacterial flora in the intestine was assessed using Enterococcus faecium, Bifidobacterium thermophilum, and Lactobacillus acidophilus. Activated charcoal showed lower binding capacity to the normal bacterial flora tested than that to E. coli O157:H7 strains. These results suggest that activated charcoal could be a good adsorbent system for the removal of VTEC and verotoxin.

Adsorption↗
PubMed2001

Infrastructure of pharmaceutical research and development in Japan.

OBJECTIVE: To examine the roles of different types of hospitals in implementation of multicenter Phase II/III trials in Japan, specifically focusing on two dichotomies: public versus private, and academic versus nonacademic. Possible explanation was sought as to why a hospital of one category was more likely to participate in specific types of trials in the Japanese medical environment. METHODS: A database containing attributes of published clinical trials (n = 217) was established from four journals featuring reports of clinical trial results. The preferences of public and academic hospitals for specific types of trials were estimated by applying a linear regression model. The trial compositions of these institutions were also estimated, taking the actual prevalence of trials in 1995 into consideration. RESULTS: Public sector hospitals, which were established for particular policy purposes in the national healthcare system, were more likely to accept trials in some fields (e.g., cardiovascular diseases, anesthesiology, antineoplastics, pediatrics) and of some kinds (e.g., Phase II rather than Phase III trials, trials supervised by the principal investigator in the public sector). Academic hospitals also showed preferences for some types of trials (e.g., cardiovascular diseases, dermatology; Phase II rather than Phase III trials). The analysis focusing on public hospitals suggested that policy purposes were achieved at least in some fields such as antineoplastics and anesthesiology. CONCLUSIONS: Japanese clinical trials were unevenly distributed between public and private sectors, and also between academic and nonacademic sectors. These data provide fundamental information about the clinical research environment for future pharmaceutical research and development strategies and policies.

Academic Medical Centers↗