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Speech-to-speech translation is a technology that connects people of different languages together and its multilingualization dramatically expands the circle of people connected. “Population” in Table 1.1a shows the potential number of people who can be part of the circle, when the corresponding language benefits from the technology. However, the same table also tells us that the languages of the world are incredibly diverse, and therefore multilingualization is not an easy task. Nevertheless, methods of processing speech sounds have been devised and developed uniformly regardless of language differences. What made this possible, is the wide commonality across languages due to the nature of language—it is a spontaneous tool created for the single purpose of mutual communication between humans who basically share the same biological hardware. This chapter will describe the multilingualization of automatic speech recognition (ASR) and text-to-speech synthesis (TTS); the two speech-related components of the three that constitute the speech-to-speech translation technology.

A cline of frequencies of the derived allele of the ALDH2 gene, which causes a deficiency of an enzyme and "facial flushing" in humans who drink alcohol, has been known among the people of the Japanese archipelago. This cline is conventionally explained by admixture with immigrants from the Asian continent occurring during the Yayoi period. Previous studies lack sufficient data from the peripheral regions of the indigenous Jomon people, and those data the ADH1B gene that is involved in the Class I ADH gene cluster and contains another variant leading to a functional change.We focused on the southwestern-most people from the Ryukyu Islands (n = 218) and those from northern Kyushu (n = 21) where the Yayoi immigrants likely arrived. We investigated both the Class I ADH and ALDH2 loci, as well as neutral genetic markers.In the Ryukyu Islands, the frequencies of the ancestral alleles in both loci were always higher than those in mainland Japan, while the frequencies of ADH1B were less than those of the derived allele. A haplotype block was not observed in ALDH2 but was in Class I ADH.Our data suggest that the derived allele of ALDH2 came with the Yayoi immigrants from the Asian continent to the Japanese archipelago. However, the derived allele of ADH1B is unlikely to be related to the Yayoi migration. Therefore, we postulate that the expansion of the derived allele of ADHIB in East Asia could be traced back to the last glacial period.

Background: Excessive consumption of alcohol is involved in the onset of pancreatitis. However, most of heavy drinkers do not always develop chronic pancreatitis. Various genetic factors appear to be involved in these individual differences in onset of chronic alcoholic pancreatitis. Here we investigated a possible association of alcoholic pancreatitis with polymorphisms of the various genes belong to the phase II detoxification enzymes responsible for metabolism of the oxidative compounds, and the several genes that have relevance to inherited pancreatitis. Methods: The subjects consisted of 53 patients with chronic alcoholic pancreatitis, 54 alcoholic patients without pancreatic dysfunction, and 42 healthy individuals. DNA was extracted from the peripheral nucleated blood cells of all subjects and genetic mutations and subtypes were analyzed by the PCR and RFLP methods. We examined the correlation between chronic alcoholic pancreatitis and variants of the phase II detoxification enzymes such as Glutathione S-transferase M1 (GSTM1), glutathione S-transferase theta 1 (GSTTI), NADPH-quinone oxidoreductase 1 (NQO1), and N-acetyl transferase (NAT2). In addition, genes of lipoprotein lipase (LPL), cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI), and cystic fibrosis transmembrane conductance regulator (CFTR) were also analyzed. Results: Frequencies of the gene deletion of GSTM1 and GSTT1 in addition to the C-allele frequency of NQO1 tended to be higher in the alcoholic patients with (AlCP) or without pancreatic dysfunction (Alc) than in the healthy controls although the difference was not significant. The NAT2 gene showed no relation with Alc and AICP patients. PSTI, LPL, PRSSI, and CFTR genes presented no association with chronic alcoholic pancreatitis. Conclusions: All genes analyzed in the present study lacked association with chronic alcoholic pancreatitis. However, the gene deletion of GSTM1 and GSTT1, and the C-allele of NQO1 cannot be ruled out for association with alcoholism.

Inspite efforts of rebirthing engineering education degradation of student achievement is progressing due to several reasons. In particular, introducing accrediting system in each university has actually contributed to improve engineering education. However, math achievement of student having different study path is unclear. Taking into account the math knowledge inevitable for bachelor engineer, present author proposes a concrete desirable math knowledge on differentiation, integral, ordinal and extraordinal differential equation, vector, tensor and complex variables at graduation, derived from his teaching career at department of mechanical engineering.

The purpose of this study is to obtain mass, spray angle and velocity distributions of fragments in debris cloud generated by oblique impacts on an aluminum alloy plate. Hypervelocity impact tests were performed with a two-stage light gas gun at Kyushu Institute of Technology. The impact angles were changed to 0°, 15°, 30°, 45° and 60°. The projectile impacted on the targets at 2 km/s. After the impact, the debris cloud was taken with flash X-rays and an ultra high-speed video camera. The fragments were then captured in a stack of polystyrene sheets. As a result, the projectile was broken up into smaller fragments by oblique impacts with the larger impact angles. Lower velocity fragments dispersed in wider spray angles according to the increase of the impact angles.

Examining curriculum among universities revealed that no significant difference in math class or related subjects can be seen. However, amount and depth of those studies, in general, differed depending on content of curriculum and the level of achievement at entrance to individual university. Universalization of higher education shows that students have many problems in learning higher level of traditional math and that the memory of math they learned quickly fades away after passing in exam. It means that further development of higher math knowledgebased engineer after graduation from universities. Under these circumstances, the present author, as one of fun of math, propose how to maintain way of thinking generated by math knowledge. What necessary for engineer is to pay attention to common books, dealing with elementary mathematics or arithmetic- related matters. This surely leads engineer to nourish math/arithmetic knowledge-based way of thinking.

There is no effective protective measure against space debris between 1 and 10 cm in diameter. Debris in this size range can perforate the pressurized walls in the International Space Station (ISS). According to the current ISS operating procedures, crews must escape from a punctured module at once. However prompt detection of the perforation hole location is difficult in the current state of the ISS. Therefore it is important to install a detection system to the locate perforation hole on a space structure for both the quick decision of escape direction and repair location. In this study, we propose a perforation hole detection system for space debris impact. This system uses a resistance film attached to the pressurized wall as an area sensor. The effectiveness of this detection system was verified by numerical analysis and pseudo-perforation hole tests but also hypervelocity impact tests.

The purpose of this study is to investigate fragment clouds generated by hypervelocity impacts (HVIs) on metallic meshes. The HVIs tests have been conducted with a two-stage light gas gun facility at Kyushu Institute of Technology. Projectiles were launched at 3 km/s. Radiographs of the fragment cloud generated by the impact of the projectile on the mesh were taken with three flash X-rays. As a result, it was found that the velocity of the fragment cloud at the cloud center of gravity was up to 35% slower than the impact velocity of the projectile.

– Objectives: The aim of this study was to determine associations of lifestyle with dental health behaviors such as tooth brushing frequency, use of extra cleaning devices, and regular dental visits to a dentist. Methods: Data were collected from 1182 dentate residents 18 years of age or older who resided in a typical farming district. The data included data on the demographic factors, dental health behavior, and various aspects of lifestyle, i.e. mental condition, alcohol consumption, smoking habit, physical activity, social activity, dietary habits, and presence of systemic diseases. Results: Multiple logistic regression analysis revealed that subjects in a younger group (18–39 years of age) and subjects who had never smoked brushed their teeth more frequently. Experience of social volunteer work and presence of systemic disease were correlated with use of extra cleaning devices. Associations of female gender with frequency of tooth brushing and use of extra cleaning devices were weakly positive. The subjects who considered dietary combination carefully and those who lived alone were predisposed to visit a dentist regularly. Conclusions: The results indicate that dental health behavior is associated with lifestyle as well as demographic factors.

It is well known that nuclear pressure vessel steel shows embrittlement under thermal aging and strong neutron irradiation. We focus on nanoscale copper-rich precipitates and try to clarify the effect of the nanoscale copper-rich precipitates on embrittlement of reactor pressure vessel steels. Our final goal is to evaluate such embrittlement from microscopic viewpoint based on atomistic simulation. In this study, we simulate interaction between motion of an edge dislocation and copper clusters using Molecular Dynamics method with a PBC, where uniform shear strain is applied to the boundaries parallel to the slip plane (1 1 2) in the system. As the results, we clarify the effects of size, distance and pinning of the copper clusters on dislocation motion.

A high strength steel shows fish-eye failure in very long life fatigue. In this region, the fatigue crack growth in ODA (Optically Dark Area) controls the fatigue process. However, ODA's formative mechanism is unknown. Therefore, to predict fatigue life of fish-eye failure, it is important to know ODA's formative mechanism. So, the present study examined for the influential factors on ODA in the fatigue process through uniaxial push-pull fatigue tests in vacuum as well as computer simulation. In experiment, vacuum environment is employed to simulate fish-eye type crack growth on surface of specimens becase of shutting off supply of air. The test results in vaccum showed that the fatigue life property of surface failure has corresponded to fish-eye fatigue life. And the site of inclusion which has fracture origin size determines whether surface failure or internal failure in vacuum. The results of fractographic observation of crack initiation showed that the rough area of surface fracture in vacuum was formed by mechanism of ODA type crack. Furthermore, the fatigue life of numerical simulation in vacuum showed that the fatigue life which was necessary to form ODA on specimen surface corresponded experimental life.

This paper will examine the applicability of the hypervelocity collision model included in the NASA standard breakup model 2000 revision to low-velocity collisions possible in space, especially in the geosynchronous regime. The analytic method used in the standard breakup model will be applied to experimental data accumulated through low-velocity impact experiments performed at Kyushu Institute of Technology at a velocity about 300m/s and 800m/s. The projectiles and target specimens used were aluminum solid balls and aluminum honeycomb sandwich panels with face sheets of carbon fiber reinforced plastic, respectively. Then, we have found that a kind of lower boundary exists on fragment area-to-mass distribution at a smaller characteristic length range. This paper will describe the theoretical derivation of lower boundary and propose another modification on fragment area-to-mass distribution and it will conclude that the hypervelocity collision model in the standard breakup model can be applied to low-velocity collisions possible with some modifications.

A number of methods of genotyping single nucleotide polymorphisms (SNPs) are currently available, ranging from the traditional restriction fragment length polymorphism (RFLP) and single-stranded conformational polymorphism (SSCP) to more sophisticated technologies. We determined the utility of three novel methods by genotyping aldehyde dehydrogenase-2 (ALDH2).DNA was isolated from blood samples of 241 control subjects and 74 patients with esophageal cancer. The utility of three novel genotyping methods-melting curve analysis using a LightCycler, SNaPshot analysis using an ABI PRISM 310 genetic analyzer, and denaturing high-performance liquid chromatography using a WAVE DNA fragment analysis system-were compared with that of conventional fluorescent-based polymerase chain reaction (PCR)-SSCP using an ALF express DNA sequencer.The frequency of the mutant ALDH2*2 allele was significantly higher in patients with esophageal cancer (27.7%) than in control subjects (16.2%; p0.01; habitual alcohol drinkers). The melting curve analysis was accurate, more rapid, and easier to use than the SNaPshot analysis or denaturing high-performance liquid chromatography analysis. Fluorescent-based PCR-SSCP proved useful for analyzing a large number of samples.Melting curve analysis using the LightCycler is suitable for the genotyping of small numbers of samples in a routine clinical setting; fluorescent-based PCR-SSCP analysis using the ALF express DNA sequencer can be used for large-scale genotyping in epidemiologic studies.

Oxidized low-density lipoproteins (ox-LDL) such as malondialdehyde-modified LDL (MDA-LDL) play an important role in the pathogenesis of atherosclerosis. This study is aimed to establish a standard enzyme-linked immunosorbent assay (ELISA) for measuring serum MDA-LDL, and evaluate its usefulness by analyzing serum samples of diabetes mellitus (DM) patients. Serum sample stability, analytical sensitivity, intra- and inter-assay precision, dilution linearity, supplementation and recovery, and interfering substances were examined. Normal reference levels in 86 healthy subjects (33 males and 53 females; average age 34.4±7.8 years) with normal lipid profiles were also determined. MDA-LDL levels in blood and serum were unstable and gradually increased during storage. However, it could be stabilized by the addition of a reagent, which included sucrose. The detection limit of the assay was 6.3 U/l. Intra- and inter-assay imprecisions were P P P

The data from a series of low-velocity collision experiments performed at Kyushu University will be re-analyzed based on the method used in the National Aeronautics and Space Administration (NASA) standard breakup model 2000 revision to be compared with the hypervelocity collision model adopted in the NASA standard breakup model. The results will indicate that the NASA hypervelocity collision model can be applied to low-velocity collisions possible in the geosynchronous regime with some simple modifications.

We have conducted research related to space debris issues, including impact experiments associated with visualization of fragment creation processes. However, we aim at those phenomena in the geosynchronous regime where the impact velocity is far lower than hypervelocity. The research purpose is to understand dispersion properties of newly created fragments to be used in the eventual orbital dispersion and debris population models. At Kyushu University, the experiments had been carried out up to velocity of 300m/s so far. However, if debris in geostationary transfer orbits should be taken into consideration, the maximum impact velocity on geostationary satellites will become up to 1500 m/s. Therefore, the experiment in 300-1500 m/s is planed to be conducted using the Two-Stage Light Gas Gun at Kyushu Institute of Technology. The similarities and differences in the experimental results from Kyushu University and Kyushu Institute of Technology are discussed.

In this study, we simulate nanoscale copper precipitation process based on the vacancy jump model using Lattice Monte Carlo (LMC) method, where an activation energy is calculated from the first neighboring interaction model. We confirmed that status of copper clustering at temperature of 300 K is different from those of 600 K and 900 K at the same potential energy decrease, and copper clusters are formed more rapidly at higher temperature. We obtained a fact that process of copper clustering consists of the two phases which are formation phase, and coalescence and/or absorption phase.

The human progesterone receptor (PR) is a ligand-activated nuclear transcription factor that mediates progesterone action in target tissues. We found a novel alternatively spliced variant (ASV) of the PR mRNA in breast cancer tissues. The deleted transcript was characterized by an out-of-frame deletion of 52 bp in exon 6 (PR delta6/2 ASV). The PR delta6/2 ASV mRNA results in a partial defect in the region of the ligand-binding domain of the hormone receptor, where conserved residues are missing from the core of the protein. To clarify the clinical significance of the PR delta6/2 ASV, we investigated the expression of this ASV in noncancerous and cancerous tissues from patients with breast cancer using RT-PCR. The novel PR delta6/2 mRNA was detected in 24 of 39 (61.5%) cancerous tissues and in 3 of 39 (7.7%) noncancerous tissues from patients with breast cancer. PR delta6/2 ASV mRNA was expressed more frequently in breast cancer tissues than in noncancerous tissues (p < 0.0001), which suggests a possible relationship between the expression of PR delta6/2 and breast cancer. Our observations may provide a novel strategy for the genetic diagnosis of breast cancer. © 2003 Wiley-Liss, Inc.

Drastic changes in society, such as quick globalization, few baby and eldering society, world wide mega competition in industries, rebuilding and shifting industrial production activity to modern and only one-oriented key technology, inevitably brings a strong demand for changing traditional education system. This paper delas with a quick summary of observing results about what has been happening outside university from a view point of education after rebirth of the world in 1990. Peer view about possibility of promoting collaborative work of engineering education between university and company is also discussed.

Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines, including levodopa. An amino acid change (Val-108-Met) in the COMT protein has been found to result in a change from high to low enzyme activity. In the present study, we genotyped 121 Japanese patients with Parkinson’s disease (PD) and 100 controls. Comparison of the allele frequencies revealed that homozygosity for the low-activity allele was significantly more common among PD patients than the controls (p = 0.047, odds ratio = 3.23). In addition, homozygosity for the low-activity allele was overrepresented in PD patients that exhibited the ‘wearing-off’ phenomenon (p = 0.045, odds ratio = 3.82) or dyskinesia (p = 0.030, odds ratio = 4.80) compared with controls, although these differences were not significant after Bonferroni’s correction. Our results may help understand the mechanism that cause complications of levodopa therapy in PD patients.

Cytochrome P-450 (CYP) enzymes have been shown to play important roles in chemical carcinogenesis. Reports have indicated that polymorphism in CYP1A1, CYP1A2, CYP2A6, CYP2E1, and CYP2D6 are associated with an altered risk of developing cancers of the lung, bladder, liver, and colon. CYP2E1 plays an important role in alcohol metabolism and participates in the metabolic activation of various carcinogens, such as N-nitrosodimethylamine. Recently, we found repeated sequences that consist of four alleles (A1, A2, A3, and A4) and six genotypes (A1/A2, A2/A2, A2/A3, A2/A4, A3/A4 and A4/A4) of the CYP2E1 gene. In the present study, we investigated whether these polymorphisms are associated with lung cancer and esophageal cancer.DNA was isolated from blood samples of 192 healthy control subjects, 85 patients with lung cancer, and 82 patients with esophageal cancer in Japanese males. DNA samples were amplified by polymerase chain reaction in the 5'-flanking region of the CYP2E1 gene and in exon 12 in the ALDH2 gene. The tandem repeat polymorphisms were examined using DNA fragment analysis. Missense mutations in exon 12 of the ALDH2 gene were examined using fluorescence-based single strand conformational change polymorphism analysis. Written informed consent was obtained from all the subjects.In the CYP2E1 gene 5'-flanking region polymorphism, patients with esophageal cancer showed significantly higher frequency of the A4/A4 genotype compared with the control subjects (p = 0.02), but no difference was found in patients with lung cancer. The frequencies of the mutant ALDH2*2 allele were significantly higher in patients with esophageal cancer (27.7%) than in healthy control subjects (7.3%; p0.0001; habitual alcohol drinkers).The distribution of genotypes and allele frequencies of the tandem repeats of the 5'-flanking region of the CYP2E1 gene was significantly different in patients with esophageal cancer.

Background: Cholecystokinin (CCK) plays an important role in the function of the central nervous system by interacting with dopamine and other neurotransmitters. We previously reported genetic variations in the promoter and coding regions of the CCKA receptor (CCKAR), CCKBR, and CCK genes and a possible association between polymorphisms of the CCKAR gene and alcoholism. In this study, association analyses were re-examined between the polymorphisms of the promoter region of the CCKAR gene and patients with alcohol withdrawal symptoms, in addition to patients with alcoholic liver injury. Methods: A total of 131 Japanese male patients with alcohol withdrawal symptoms, 70 Japanese patients with alcoholic liver injury, and 98 age-matched Japanese male controls (nonhabitual drinkers) were examined using polymerase chain reaction-based single strand conformational polymorphism and sequencing analyses. Results: Significant differences between patients with hallucination and controls were found in the allele frequencies at the -388 and -85 loci of the CCKAR gene (p = 0.0095, p = 0.0087, respectively), but these differences were not significant after Bonferroni correction for multiple testing. In contrast, the frequency of the homozygous genotype -85CC was significantly higher in hallucination-positive patients than in controls (p = 0.0031) and in patients with hallucination accompanying delirium tremens than in controls (p = 0.0022), and these differences were significant after Bonferroni correction. Conclusions: The data from the case control suggest that polymorphisms of the promoter region of the CCKAR gene do not play a major role in the pathogenesis of alcohol withdrawal symptoms or alcoholic liver injury. However, a significant association was found between polymorphism at the -85 locus of the CCKAR gene and patients with hallucination, and especially patients with hallucination accompanying delirium tremens.

The human γ-aminobutyric acid type B (GABAB) receptor gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiologic roles. In the present study, association analyses of genetic polymorphisms of the GABAB receptor gene with schizophrenia were carried out in 102 unrelated schizophrenic patients and 100 healthy controls, using a polymerase chain reaction-based, single-strand conformational polymorphism analysis. Although the Ala20Val and Gly489Ser mutations were not found in our samples, we found a novel polymorphism of (AC)n dinucleotide repeats located approximately 1.6 kb upstream from the translational start site. No significant difference in allele frequencies was found between controls and patients with schizophrenia (P = 0.0587) using the Monte Carlo method. Significant differences were found between controls and patients with continuous-course schizophrenia (P = 0.0019), and between controls and patients with a positive family history of psychoses (P = 0.0015). These differences, however, were not significant after Bonferroni correction. These data did not support our hypothesis that polymorphisms of the GABAB receptor gene may confer vulnerability for schizophrenia. © 2002 Wiley-Liss, Inc.

Cholecystokinin A receptors (CCKAR) modulate CCK-stimulated dopamine release, and mutations in the CCKAR gene may predispose affected individuals to schizophrenia. Our previous study suggested that -286A>G polymorphism (previously named 201A>G) in the CCKAR gene promoter is associated with schizophrenia. In the present study, we carried out a further investigation of the promoter and intron 1 of the CCKAR gene. In addition to polymorphisms reported previously (-333G>T, -286A>G, -241G>A, 773A>T, and 779T>C), two novel polymorphisms (-388(GT)(8)>(GT)(9) and -85C>G) were identified. These polymorphisms were in a linkage disequilibrium. Association analyses between schizophrenic patients and controls revealed that the frequencies of the A allele and AA genotype at the -286 loci, as well as the frequency of the GG genotype at the -333 loci, were significantly higher in patients than in controls. Furthermore, patients with paranoid type schizophrenia, auditory hallucinations, or a positive family history had a significantly higher frequency of the -286A allele than the control group. The results supported our previous data, and suggest the possible involvement of the -333G>T and the -286A>G polymorphisms in the promoter region of the CCKAR gene in the predisposition to schizophrenia.

Cholecystokinin (CCK) plays an important role in the functioning of the central nervous system via an interaction with dopamine and other neurotransmitters. The dopaminergic system has been implicated in the maladaptive behaviors associated with drugs of abuse (e.g., alcohol and cocaine). We analyzed genetic variations in the promoter and coding regions of the CCK, CCKA-receptor (CCKAR) and CCKB-receptor (CCKBR) genes, and performed association analyses with alcoholism.A total of 214 Japanese male patients with alcoholism (93 with delirium tremens, 49 with hallucinations, 38 with seizures and 83 without any of these symptoms) and 98 age-matched Japanese male controls were examined using PCR-based Single Strand Conformational Polymorphism (SSCP) analysis.A total of 8 variants in the CCK gene, 11 variants in the CCKAR gene and 9 variants in the CCKBR gene were detected in the present study. Nominally significant differences between alcoholics and controls were found at the -85 locus of the CCKAR gene (p = .035). In addition, patients displaying hallucinations showed a higher frequency of the homozygous genotype of the allele (GT)8 at the -388 locus of the CCKAR gene (p = .042) and homo- and heterozygous genotypes of the T allele at the -333 locus (p = .025), relative to other patients. However, these differences were not significant after Bonferroni correction.Our data suggest that polymorphisms of the CCK, CCKAR and CCKBR genes do not play a major role in alcohol withdrawal symptoms (even though significant associations were found among polymorphisms at the -388 and -333 loci of the CCKAR gene and hallucinations, the rate was nonsignificant after Bonferroni correction).

Background: Recently, a restriction fragment length polymorphism in the regulatory region of the CYP2EI gene was identified. It has been suggested that the polymorphism is associated with the elevated activity of the cytochrome P-450 2E1 (CYP2E1) enzyme in obese or alcoholic subjects. However, significance of the polymorphism in connection with alcoholism has not been studied. In the present study, we have characterized these repeated sequences in the 5'-untranslated region of the CYP2E1 gene in Japanese subjects and North American white subjects and investigated whether these polymorphisms are associated with drinking habits and alcoholism. Methods: DNAs were isolated from blood samples of 192 Japanese nonalcoholics and 202 alcoholics as well as 125 North American white nonalcoholics. DNA samples were amplified by polymerase chain reaction and subjected to a fluorescent-based single-strand conformational change polymorphism analysis, DNA fragment analysis, and polymerase chain reaction-direct sequencing. Results: Four alleles (A1-A4) were found, which were differentiated by the six subunits (L1, L2, L3, L4, S1, S2) based on the size difference and nucleotide replacement. A2 and A4 alleles were observed in the two ethnic groups (A2: Japanese subjects, 0.752; white subjects, 0.976; A4: Japanese subjects, 0.227; white subjects, 0.016). However, A1 allele was found only in North American white subjects (0.008), and A3 allele was detected only in Japanese subjects (0.021). Allele frequencies were significantly different between the two ethnic groups (p < 0.0001). Distribution of genotypes between Japanese nonalcoholics and alcoholics were not significantly different. Also, no significant difference for the allele frequencies was observed between Japanese moderate drinkers and heavy drinkers. Conclusions: Our data suggested no association among the polymorphic repeats, drinking behavior, and alcoholism. Allele frequencies were significantly different between Japanese subjects and North American white subjects.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Shoji Harada and Dharam P. Agarwal. The presentations were (1) Mutations in the exons, exon-intron junctions, and promoter regions of human CYP2E1 gene and alcoholism, by Fumio Nomura; (2) Genetic variability in alcohol metabolism and drinking habits in Japanese, by Shoji Harada; (3) Genetic studies of alcohol dependence using alcoholics with inactive ALDH2, by Susumu Higuchi; and (4) Alcohol consumption, apolipoprotein polymorphisms, and cardiovascular disorders, by Dharam P. Agarwal.

Recent studies have revealed that GSTM1 and M2 of the μ-class glutathione S-transferases catalyze a glutathione conjugate of catechol o-quinones including dopachrome, noradrenochrome, and adrenochrome under physiological conditions. Reduced or negative levels of activity amongst these enzymes would lead to an excess of neurotoxic compounds of catecholamine o-quinones. A defect in the mechanisms responsible for this form of detoxification may contribute to the development of certain forms of schizophrenia. We have performed a case-control study to explore the association between schizophrenia and polymorphism of the GSTM1 gene. DNA samples were obtained from 87 unrelated patients with schizophrenia who met the DSM-IV criteria for schizophrenia and from 176 control subjects. Individuals of both groups were ethnically Japanese and were from the same district. GSTM1 polymorphism was determined using the polymerase chain reaction method. The frequency of the GSTM1*0 allele was significantly higher amongst the patients with schizophrenia compared to controls (P = 0.0075). Moreover, the incidence of the GSTM1*0 was significantly higher amongst the schizophrenic patients classified as disorganized type (P = 0.0008), relative to the control sample. Our findings suggest that the GSTM1*0 is associated with an increased susceptibility to schizophrenia, particularly disorganized type of the disease. It is therefore likely that the GSTM1 gene deletion constitutes to vulnerability for disease states of this kind, rather than being the direct cause of schizophrenic conditions.

Mode III fatigue crack is usually observed at the root of circumferentially notched round bar. As the crack grows in the depth direction of specimen, the growth rate of crack decreases. In this respect, crack mode transition from mode III to mode I is understood responsible. However, quantitative evaluation on crack mode transition has been hardly done. Therefore, values of stress intensity factor KI under mode III fatigue crack growth tests on a low carbon steel were calculated with using principal stress, as crack mode transition began. Then KI values were compared with crack growth rate curve of mode I. As the result, it was observed that the condition of crack mode transition was given by the crack growth rate curve of mode I.

The human synapsin III gene, located on chromosome 22q12–13, has previously been reported to indicate a susceptibility for schizophrenia. Noval rare variants (Thr136Thr in exon 3, Pro468Ser, Glu525Gln and Pro534Leu in exon 12, and 1769 G/C in the untranslated region of exon 13) were found in addition to the polymorphic variant (–196 G/A in the promoter region). No significant differences in genotypic or allelic frequencies of the –196 G/A polymorphism were found between 87 unrelated schizophrenic patients and 100 healthy controls, even when the patients were diagnostically subdivided into subtypes and course specifiers. Furthermore, allelic frequencies of the GATG repeat in intron 1 were not significantly different between the patients and the controls. These results suggest that synapsin III gene polymorphisms are not associated with schizophrenia.

To examine the interaction of sodium intake with genetic variations of the angiotensinogen gene and hypertension.A community-based case-reference study.Two rural Japanese communities.Non-overweight and non-drinking Japanese men and women: 229 hypertensives and 229 age-, sex- and community-matched normotensives aged 32 to 83 years.Polymorphisms of the angiotensinogen gene detected by an allele-specific polymerase chain reaction. A priori hypothesis is individuals with 174M (threonine-to-methionine substitution) or 235T (methionine-to-threonine substitution) allelic variations may have an elevated risk of hypertension when they have a high sodium intake, estimated by 24-h urine collection and a dietary questionnaire.The genotypic frequency of the haplotype including both the 174M and 235T alleles was higher among hypertensives than among normotensives (23 versus 14%, P= 0.02). The frequency of the 174M allele was specifically higher among hypertensives than normotensives (12 versus 7%, P=0.01), and the odds ratio of hypertension associated with the 174M (versus 174T) allele was 1.8 [95% confidence interval (CI) 1.1-3.0, P=0.01]. The frequency of the 235T allele did not vary between the two groups (80 versus 82%, P= 0.40). The relationship between the 174M allele and hypertension was more evident among persons who had higher urinary sodium excretion (= 166 mmol/day) than those with lower excretion (166 mmol/day): odds ratio 2.5 (95% CI, 1.2-5.2), P=0.01 versus 1.5 (95% CI, 0.7-3.1), P= 0.31; P for interaction = 0.04, and this trend was primarily observed for early-onset hypertension (55 years at onset). A similar but nonsignificant association was observed when stratified using present and past sodium intake scores derived from questionnaires.Angiotensinogen genotype may affect the development of early-onset hypertension among Japanese, particularly in those who have a high sodium intake.

Background: Although the mutant low-Km acetaldehyde dehydrogenase (ALDH2) allele (ALDH2 2 ) with reduced capacity to metabolize acetaldehyde offers biological protection against alcoholism and subsequent alcohol-induced organ damage in many individuals, a significant proportion of individuals with heterozygote of the normal and mutant ALDH2 gene (ALDH2 1 /2 2 ) consume excessive amounts of alcohol. Indeed, it has been postulated that habitual drinkers with ALDH2 1 /2 2 may be at a higher risk for alcoholic liver disease than those with ALDH2 1 /2 1 . In this study, we determined how representative biological markers of alcoholism (y-glutamyltransferase [GGT], carbohydrate-deficient transferrin [CDT], and the mean corpuscular volume of erythrocytes [MCV]) differ with respect to theALDH2 genotypes in Japanese habitual drinkers. Methods: We obtained genomic DNA samples from 227 Japanese men with various drinking habits. ALDH2 genotypes were determined by allele-specific polymerase chain reaction. GGT, CDT, and MCV were determined and compared between ALDH2 1 /2 1 and ALDH2 1 /2 2 habitual drinkers who consumed more than 66 g of alcohol per day for more than 5 years. We measured CDT by anion-exchange chromatography followed by turbidity immunoassay by using a commercially available assay kit (Axis %CDTTIA). Results: CDT levels were comparable between the two groups. GGT activities were significantly greater in ALDH2 1 /2 1 than in ALDH2 1 /2 2 habitual drinkers (81 ± 85 vs. 53 ± 40 IU/liters,p < 0.02). MCV values, on the other hand, were significantly larger in ALDH2 1 /2 2 than in ALDH2 1 /2 1 subjects (98.2 ± 5.8 vs. 95.8 ± 4.2 fl, p = 0.02). When we used elevation of either CDT or GGT to detect habitual drinking in ALDH2 1 /2 1 and 2 1 /2 2 subjects, the sensitivities were 57% and 46%, respectively. CDT levels were similar between habitual drinkers with normal aspartate aminotransferase levels and those with elevated levels. Conclusion: GGT and MCV, but not CDT, differ with respect to the ALDH2 genotypes in Japanese male habitual drinkers. ALDH2 genotypes should be considered when interpreting data on biological markers of alcoholism.

The transcription factor activator protein 2 (AP-2) gene is a possible candidate gene for schizophrenia, since it maps near D6S470, a marker on chromosome 6p24 that provided evidence of linkage to schizophrenia. In the present study we analyzed the promoter region and the whole coding region of the human AP-2 gene in order to identify genetic variations that may lead to the modification of AP-2 expression or the alteration of protein function, contributing to schizophrenia or particular schizophrenic phenotypes. Genomic DNA was isolated from the whole blood samples of 87 unrelated schizophrenics and 100 healthy controls. Polymerase chain reaction (PCR) was performed, using 15 primer sets that spanned the promoter region and the whole coding region, and amplified products were screened by single-strand conformational polymorphism (SSCP) analysis. Aberrant SSCP patterns were analyzed by direct sequencing. Three novel polymorphisms were found in the promoter region; two relatively common (-90G--C, -803G--T) and one rare (-1769G--A). Polymorphic status at both loci suggested strong linkage disequilibrium between the -90G and -803G alleles, and between the -90C and -803T alleles. Although no significant differences in genotypic and allelic frequencies at the -90 and -803 loci were found between patients and controls, significant differences in the distribution of genotypes at the -90 (P = 0.008) and -803 (P = 0.037) loci were observed in patients with an episodic course compared with controls. However, the difference for the -803 locus was not significant after Bonferroni correction for multiple comparisons. Our data provided no direct evidence of an association between schizophrenia and the polymorphisms of the AP-2 gene, although the positive result at the -90 locus in schizophrenics with an episodic course is potentially interesting.

Parkinson's disease (PD) is characterized by major alterations of neurotransmitter activity due to damage of the substantia nigra. Changes in neuropeptide concentration within the basal ganglia may play an important role in the putative dopaminergic-peptidergic interactions associated with the disease. Cholecystokinin (CCK) modulates the release of dopamine in the mesolimbic pathway and affects dopamine-related behavior. We analyzed genetic variations in the CCK gene, in both the coding and promoter region, in order to investigate the role of polymorphism in idiopathic PD. Four polymorphic sites of the CCK gene (-196G/A, -45C/T, 1270C/G, 6662C/T) were found in PD patients and controls. Complete linkage disequilibrium was observed between the -45 locus and the 1270 locus, and also a possible linkage disequilibrium was found between the -45 and -196 loci. A significant difference was found in the distributions of three identified genotypes at the -45 locus between 116 PD patients and 95 age-matched control subjects (chi2 = 7.95, p = 0.018, Bonferroni correction; p = 0.054). In addition, a significant difference was obtained amongst the three genotypic groups at the -45 locus when compared between PD patients who experienced hallucinations (n = 23) and those (n = 93) who did not (chi2 = 8.08, p = 0.018, Bonferroni correction, p = 0.126). Our data suggested that mutations at the -45 locus in the promoter region of the CCK gene may influence vulnerability to hallucinations in PD patients treated with L-dopa.

Background: Human mitochondrial aldehyde dehydrogenase (ALDH2) is a major enzyme responsible for the oxidation of acetaldehyde derived from ethanol metabolism. The human ALDH2 gene shows genetic polymorphism at position 1510 with a G to A transition in exon 12. This mutation leads toALDH2 enzyme deficiency and protection against alcoholism. As yet, no polymorphism for the promoter region of the ALDH2 gene has been reported. Methods: We analyzed 600 nucleotides of the promoter region in addition to exon 12 from 571 Japanese, 68 Chinese, 80 Myanmar, 60 Mongolians, and 82 North-American Caucasians using single-strand conformational change polymorphism (SSCP) analysis and the polymerase chain reaction (PCR). PCR products that showed an aberrant banding pattern detected by the SSCP analysis were subjected to PCR direct sequencing. Results: A novel polymorphism at -357 with a G to A substitution was found in all the population groups, including North-American Caucasians. In addition, the polymorphic status in the promoter and exon 12 suggested linkage disequilibrium between the two loci, which indicated that among Japanese, the ALDH2 * 2 allele is linked to the G promoter allele, and the ALDH2 * 1 allele is linked to the A allele. A total of 206 healthy male controls and 185 alcoholic male patients with the homozygous ALDH2 * 1 genotype were analyzed for the polymorphism in the promoter. Genotypic frequencies of GG, GA, and AA for alcoholics were 54.1%, 44.3%, and 1.6%, and those for controls were 52.9%, 40.3%, and 6.8%, respectively. The A allele frequencies for alcoholics and controls were 0.24 and 0.27, respectively. A X 2 test for the entire 3 x 2 table indicated significant variations in the three genotypes (X 2 = 6.40, p < 0.05). However, no significant difference in allelic frequencies between the two groups was observed. Conclusion: This new polymorphism in the ALDH2 promoter is present in all populations studied. Further analysis in other ethnic groups is necessary to establish this as an additional risk factor for alcoholism.