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Background The presence of the less-active form of alcohol dehydrogenase- 1B encoded by ADH1B *1/*1 (vs. *2 allele) and active form of aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2 *1/*1 (vs. *2 allele) increases the risk of alcoholism in East Asians. Methods The subjects in this cross-sectional survey were 1,902 Japanese alcoholic men (≥40 years) who underwent ADH1B/ ALDH2 genotyping. Results Age-adjusted daily alcohol consumption did not differ according to the ADH1B/ ALDH2 genotypes. The age-adjusted odds ratios ( AORs; 95% confidence interval) for liver cirrhosis ( LC; n = 359, 1.58 [1.19 to 2.09]), chronic calcific pancreatitis ( CP; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus ( DM; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B *2 allele carriers than in the ADH1B *1/*1 carriers. The AORs for LC (1.43 [1.01 to 2.02]), CP (1.68 [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension ( HT; n = 495, 1.52 [1.11 to 2.07]) were higher in the ALDH2 *1/*1 carriers than in the ALDH2 *1/*2 carriers. The ADH1B *2-associated AOR for LC was 2.08 (1.46 to 2.94) among those aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over, and the interaction between ADH1B genotype and age on the LC risk was significant ( p = 0.009). When the group with non- LC and no/mild fibrosis was used as controls, the ADH1B *2-associated AORs increased according to the severity of their liver disease: 1.67 (1.32 to 2.11) for the group with non- LC and serum type IV collagen values ≥200 ng/ml, 1.81 (1.24 to 2.63) for the group of Child- Pugh class A LC, and 3.17 (1.98 to 5.07) for the group with Child- Pugh class B/ C LC. Anti-hepatitis C virus ( HCV) antibody was positive in 103 patients, and the groups with a high anti- HCV antibody titer and either the ADH1B *2/*2 genotype or the ALDH2 *1/*1 genotype had the highest AORs (8.83 and 4.90, respectively). The population attributable fraction ( PAF) due to the ADH1B *2 allele was 29% for LC, 47% for CP, and 27% for DM, and the PAF due to the ALDH2 *1/*1 genotype was 26% for LC, 34% for DM, and 30% for HT. Conclusions The ADH1B *2 allele increased the AORs for LC, CP, and DM of the alcoholics, and the ALDH2 *1/*1 genotype increased their AORs for LC, DM, and HT. HCV infection and genetic susceptibility had a synergistic effect on the AOR for LC. [ABSTRACT FROM AUTHOR]

Background The calories in alcoholic beverages consumed by alcoholics are a major energy source and a strong modifier of their body weight. Genetic polymorphisms of alcohol dehydrogenase-1B ( ADH1B) and aldehyde dehydrogenase-2 ( ALDH2) affect susceptibility to alcoholism and may affect body weight via gene-associated differences in fuel utilization in alcoholics. Methods We evaluated associations between ADH1B/ ALDH2 genotypes and the body weight and body mass index ( BMI) of 1,301 Japanese alcoholic men at the time of their first visit to an addiction center. Results Median (25th to 75th) caloric intake in the form of alcoholic beverages was 864 (588 to 1,176) kcal/d. Age-adjusted caloric intake did not differ according to ADH1B/ ALDH2 genotypes. The body weight and BMI values showed that the ADH1B*2/*2 and *1/*2 carriers ( n = 939) were significantly leaner than the ADH1B*1/*1 carriers ( n = 362) irrespective of age, drinking, smoking, and dietary habits. The age-adjusted body weight values of the ADH1B*2/*2, ADH1B*1/*2, and ADH1B*1/*1 carriers were 58.4 ± 0.4, 58.7 ± 0.5, and 63.6 ± 0.5 kg, respectively ( ADH1B*2 vs. ADH1B*1/*1 carriers, p < 0.0001), and the corresponding BMI values were 21.0 ± 0.1, 21.0 ± 0.1, and 22.9 ± 0.2 kg/m2, respectively ( ADH1B*2 vs. ADH1B*1/*1 carriers, p < 0.0001). No effects of inactive ALDH2 on body weight or BMI were observed. A multivariate analysis showed that BMI decreased by 0.35 per 10-year increase in age, by 1.73 in the presence of the ADH1B*2 allele, by 1.55 when the preferred beverage was whiskey, and by 0.19 per +10 cigarettes/d and that it increased by 0.10 per +22 g ethanol (EtOH)/d and by 0.41 per increase in category of frequency of milk intake (every day, occasionally, rarely, and never). The increase in BMI as alcohol consumption increased was significantly smaller in the ADH1B*2 group than in the ADH1B*1/*1 group ( p = 0.002). Conclusions ADH1B genotype was a strong determinant of body weight in the alcoholics. The more rapid EtOH elimination associated with the ADH1B*2 allele may result in less efficient utilization of EtOH as an energy source in alcoholics. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effects of gadolinium-based contrast agent (GBCA) on 1H-magnetic resonance spectroscopy (MRS) of the breast at 3.0-T. Materials and Methods: Patients ( n = 98) with breast cancer (98 lesions) underwent MRS (point-resolved spectroscopy sequence [PRESS]; TR/TE, 2000/100 msec; voxel size, 15 × 15 × 15 mm) before the administration of GBCA. In 52 of those patients, MRS was also performed after the administration of GBCA. The voxel-of-interest (VOI) was placed by referring to the noncontrast-enhanced MRI (diffusion-weighted images combined with fat-suppressed T2-weighted images). We reviewed and graded the appropriateness of VOI location compared to the correlating enhancement lesions. Integral values of the choline peak at a frequency of 3.2 ppm on MRS were compared before and after the administration of GBCA. Results: The VOI was placed correctly in 64 lesions (65%), although the VOI was placed outside the targeted lesion in 34 lesions (35%). The integral value of the choline peak on MRS decreased significantly after the administration of GBCA ( P < 0.001). Conclusion: Accumulation of GBCA in breast cancer could affect the choline peak on MRS. MRS of breast cancer at 3.0-T can be recommended to be acquired before contrast-enhanced study; however, some problems remain in VOI placement with reference to the noncontrast-enhanced study. J. Magn. Reson. Imaging 2012;35:717-722. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of quantitative 1H MR spectroscopy (MRS) using the external standard method to predict the pathological response to neoadjuvant chemotherapy with an anthracycline-based regimen in breast cancer patients. Materials and Methods: Sixteen patients with breast cancer were included. Tumor response to chemotherapy was evaluated after the second cycle using MRI and MRS. Final histopathology following surgery after four cycles of chemotherapy served as reference. Results: The average normalized choline (Cho) signal was 1.2 (range, 0.40 to 2.8). There were no significant differences in the baseline tumor size and normalized Cho signals between the pathological responders (n = 8) and nonresponders (n = 8). The reduction rates of the normalized Cho signal were statistically significantly different between the pathological responders and nonresponders ( P = 0.004), whereas the reduction rates of the lesion size were not significantly different between the two groups. When 40-50% of the reduction rates of the normalized Cho was chosen as the cutoff value, the positive and negative predictive values of MRS were 89% (8/9) and 100% (7/7), respectively. Conclusion: The changes in Cho after the second cycle of chemotherapy as determined by quantitative MRS may be more sensitive than changes in the tumor size to predict the pathological response. J. Magn. Reson. Imaging 2010;31:895-902. ©2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: The risk of metachronous gastric cancer is high in Japanese with esophageal squamous cell carcinoma (SCC), especially in alcoholic men, suggesting a common background underlying the gastric and esophageal cancers. Methods: Endoscopic follow-up ranging from 7 to 160 months (median, 47 months) after the initial diagnosis was performed in 99 Japanese gastric-cancer-free alcoholic men (56.8 ± 6.4 years) with esophageal SCC detected by an endoscopic screening examination. Chronic atrophic gastritis (CAG) assessed by the serum pepsinogen test and Helicobacter pylori status was compared between 90 of the 99 esophageal SCC cases and 180 age-matched Japanese gastric- and esophageal-cancer-free alcoholic men. Results: The serum pepsinogen test showed a higher seroprevalence of severe CAG among the cases than among the age-matched controls (35.4% vs. 14.2% for H. pylori-seropositive, 71.4% vs. 7.7% for H. pylori-indeterminate, and 17.1% vs. 9.8% for H. pylori-negative, respectively; H. pylori status-adjusted p = 0.0008), whereas their H. pylori status was similar. The accelerated progression of severe CAG observed in the Japanese alcoholic men with esophageal SCC suggests the existence of common mechanisms by which both esophageal SCC and H. pylori-related severe CAG develop in this population. Metachronous gastric adenocarcinoma was diagnosed in 11 of the 99 gastric-cancer-free patients, and the cumulative rate of metachronous gastric cancer within 5 years was estimated to be 15% according to the Kaplan–Meier method. The age-adjusted hazard ratios were 7.87 (95% confidence interval: 1.43 to 43.46) and 4.84 (1.16 to 20.21), respectively, in the patients with severe CAG in comparison with those without CAG and those without severe CAG. Inactive heterozygous aldehyde dehydrogenase-2, a very strong risk factor for esophageal SCC in the alcoholics, was not associated with an increased risk of metachronous gastric cancer. Conclusions: Accelerated development of severe CAG at least partially explained the very high frequency of development of metachronous gastric cancer in this population. [ABSTRACT FROM AUTHOR]

In this study, we assessed the physiological changes after exercising or cooling skeletal muscles on the basis of the apparent diffusion coefficient (ADC) values in magnetic resonance (MR) diffusion-weighted images (DWIs). DWIs of the ankle dorsiflexors were acquired with a 1.5-T MR device before and after exercising (22 subjects) or cooling (19 subjects). The exercise comprised a 5-min walk with the ankles dorsiflexed and a 30-time ankle dorsiflexion. Cooling (0 degrees C) of the ankle dorsiflexors was performed for 30 min. ADC values were calculated as ADC1-reflecting diffusion and perfusion and ADC2-approximating the true diffusion coefficient of the ankle dorsiflexors before and after exercising or cooling. ADC1 and ADC2 significantly increased with exercise and decreased with cooling (P < 0.05). Considering both diffusion and perfusion, ADC values allowed us to evaluate the intramuscular changes induced by exercising or cooling in terms of the motion of water molecules and microcirculation. [ABSTRACT FROM AUTHOR]

East Asian case–control studies have shown a strong relationship between alcohol consumption combined with inactive heterozygous aldehyde dehydrogenase-2 ( ALDH2* 1/* 2) and the development of squamous cell carcinoma (SCC), especially multiple SCC, of the upper aerodigestive tract (UADT). This study aimed to identify determinants of the development of metachronous SCC in the UADT in alcoholics with esophageal SCC. Follow-up endoscopic examinations were carried out 4–160 months (median, 41 months) after initial diagnosis in 110 Japanese alcoholic men with esophageal SCC diagnosed by screening using endoscopy combined with oropharyngolaryngeal inspection and esophageal iodine staining. ALDH2* 1/* 2 was significantly associated with the presence of multiple primary intraesophageal SCC at the time of initial diagnosis. Metachronous primary SCC of the esophagus was diagnosed in 29 of the 81 patients whose initial esophageal SCC was treated by endoscopic mucosal resection alone, and metachronous primary SCC of the oropharyngolarynx was diagnosed in 23 of the 99 patients without synchronous primary SCC of the oropharyngolarynx at the time of initial diagnosis. The risks of metachronous esophageal SCC and oropharyngolaryngeal SCC were significantly higher in ALDH2* 1/* 2 heterozygotes than in ALDH2* 1/* 1 homozygotes (age-adjusted and alcohol-adjusted hazard ratio = 3.38 [95% confidence interval: 1.45–7.85] and 4.27 [1.42–12.89], respectively), and in patients with multiple intraesophageal SCC at the time of initial diagnosis than in patients with a solitary intraesophageal SCC (3.09 [1.41–6.78] and 3.25 [1.41–7.47], respectively). ALDH2* 1/* 2 and multiple synchronous intraesophageal SCC were found to be predictors of metachronous SCC in the UADT in this population. ( Cancer Sci 2008; 99: 1164–1171) [ABSTRACT FROM AUTHOR]

Chronic and excessive consumption of alcohol is an important factor responsible for the onset of pancreatitis. However, the incidence of chronic pancreatitis in heavy drinkers differs in individuals, suggesting that these individual differences may involve various genetic and environmental factors. In the present study, we investigated an association of alcoholic pancreatitis with polymorphisms of the various genes related to metabolism of the oxidative compounds. We analyzed polymorphisms of NADPH-quinone oxidoreductase 2 (NQO2), multidrug resistance 1 (MDR1), alcohol dehydrogenase 1B (ADH1B) and lipoprotein lipase (LPL). The subjects consisted of 53 patients with chronic alcoholic pancreatitis (AlCP), 54 alcoholic patients without pancreatic dysfunction (Alc), and 42 healthy individuals. DNA samples were prepared from the peripheral blood of all subjects, and the genetic mutations were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The ADH1B gene frequencies were significantly different between healthy controls and Alc patients ( P < 0.001), and also between AlCP and Alc patients ( P < 0.05). However, no significant difference was found between healthy controls and AlCP patients. The gene frequencies of MDR1 (3435C > T) and MDR1 (2677G > A/T) of patients with AlCP or Alc were different when compared with healthy controls, although the difference was not significant. The NQO2 and LPL genes showed no relation with Alc and AlCP patients. The ADH1B* 1 gene frequency in AlCP was significantly lower compared with Alc. We speculate that the ADH1B* 1 gene may function by reducing vulnerability to the onset of alcoholic pancreatitis. Other genes analyzed in the present study lacked association with AlCP. [ABSTRACT FROM AUTHOR]

Background: Gastric carcinoma occurs at a high rate in alcoholic Japanese men. Inactive heterozygous aldehyde dehydrogenase-2 ( ALDH2* 1/2* 2) and macrocytosis (mean corpuscular volume [MCV] ≥ 106 fl) enhance the risk for esophageal carcinoma, which frequently occurs with gastric carcinoma in this population. Whether alcoholism affects Helicobacter pylori-induced chronic atrophic gastritis (CAG) is unknown. Methods: This study of Japanese alcoholic men with ( n = 45) and without ( n = 281) gastric carcinoma included assessment of H. pylori IgG antibody, serum pepsinogen-confirmed CAG, MCV, and ALDH2 genotype. Results: The gastric carcinoma cases had a significantly higher age-adjusted prevalence of H. pylori-positivity (78% vs 57%), CAG (78% vs 42%), ALDH2* 1/2* 2 (36% vs 14%), MCV ≥106 fl (38% vs 20%), and concurrent esophageal/oropharyngolaryngeal carcinoma (18% vs 5%) than controls. Among gastric cancer-free controls, the prevalence of CAG was higher than generally reported in Japan, regardless of H. pylori status ( H. pylori-positive, 56% vs 35–36% for Japanese general population; H. pylori-negative, 8% vs 1–3%). Alcoholism may accelerate the progression of CAG. Each of these factors increased the risk of gastric carcinoma (O Rs = 3.7 for H. pylori-positive, 2.7 for non-severe CAG, 8.7 for severe CAG, 3.5 for ALDH2* 1/2* 2, 2.5 for MCV ≥106 fl, and 3.7 for concurrent carcinoma). A multivariate analysis showed that CAG and ALDH2* 1/2* 2 were independently related to the risk of gastric carcinoma. Combinations of CAG and ALDH2* 1/2* 2 showed greater risks of gastric carcinoma (O Rs = 4.0 for non-severe CAG alone, 17.6 for severe CAG alone, 9.7 for ALDH2* 1/2* 2 alone, 17.1 for non-severe CAG plus ALDH2* 1/2* 2, and 39.2 for severe CAG plus ALDH2* 1/2* 2). Conclusions: Combining blood tests for H. pylori, CAG, MCV and ALDH2 genotype could offer a new means of predicting risk of gastric carcinoma in Japanese alcoholic men. [ABSTRACT FROM AUTHOR]

Melanosis is frequently observed in the upper aerodigestive tract of Japanese alcoholic men, and the prevalences of squamous cell dysplasia and SCC in the upper aerodigestive tract of Japanese alcoholic men are high. This study evaluated associations between melanosis and both neoplasms of the upper aerodigestive tract and factors contributing to the development of melanosis in Japanese alcoholic men. Endoscopic screening of 643 Japanese alcoholic men (aged 50–79 years) was combined with oropharyngolaryngeal inspection and esophageal iodine staining, and ALDH2 genotyping was carried out in 425 of them. Melanosis was frequently (20.8%) observed in the upper aerodigestive tract. The palate was the most common site of melanosis (11.2%), followed by the pharynx (9.5%), and by the esophagus (7.0%). The incidence of melanosis was higher in those with esophageal dysplasia (31/126, 24.6%), esophageal SCC (19/42, 45.2%), and oropharyngolaryngeal SCC (8/14, 54.1%) than in cancer- and dysplasia-free controls (69/437, 15.8%). The presence of melanosis was associated with a higher risk of esophageal dysplasia, esophageal SCC, and oropharyngolaryngeal SCC (OR 1.69, 4.03, and 6.61, respectively). Multivariate analysis showed that older age, heavier smoking, and heterozygosity for inactive ALDH2 were positively associated with the presence of melanosis. The presence of melanosis indicates a high risk for neoplasms in the upper aerodigestive tract of Japanese alcoholic men. Melanosis and neoplasms have the same causes, including older age, heavy smoking, and high acetaldehyde exposure. ( Cancer Sci 2006; 97: 905–911) [ABSTRACT FROM AUTHOR]

Background/Aims: The pancreas is often damaged by excessive alcohol consumption. Because alcohol-related problems and diabetes mellitus (DM) are increasing in Japan, this cross-sectional study was designed to investigate how pancreatic volume (PV, calculated using multi-slice helical computed tomography) represents alcohol consumption and both endocrine and exocrinepancreatic function among alcoholics. Methods: Consenting male and female inpatients undergoing psychiatric therapy for alcoholism from June 2003 to May 2004 were subjected to four-slice MCT to determine PV. Fasting plasma glucose (FPG) and serum lipase levels were examined for endocrine and exocrine pancreatic functions, respectively. Results: The average PVs of 535 male and 117 female patients (57.2 ± 21.91 ml and 54.5 ± 17.56 ml, respectively) were related to age and height (H) but not to body weight (W). Lipase values had a strong relationship with PV/W. Multiple regression analysis revealed weak associations between PV and both daily ethanol consumption and duration of habitual drinking. The diagnosis of DM in 109 of these alcoholics was more strongly associated with the PV/W value than with PV or PV/H. Conclusion: The association of PV with endocrine and exocrine functions suggests new markers, especially PV/W, for the assessment of DM among alcoholic patients. Copyright © 2005 S. Karger AG, Basel and IAP [ABSTRACT FROM AUTHOR]

Background. Esophageal melanosis is often observed in alcoholic Japanese men, in whom the prevalence of squamous cell dysplasia and carcinoma (SCC) in the upper aerodigestive tract are high. This study evaluated the associations of esophageal melanosis with these neoplasms, and the factors contributing to the development of esophageal melanosis in this population. Methods. Endoscopic screening was combined with esophageal iodine staining in 1535 alcoholic Japanese men (aged 40-79 years), of whom 1007 underwent aldehyde dehydrogenase-2 (ALDH2) genotyping. Results. Fifty patients (3.3%) were diagnosed with esophageal melanosis, which had a higher incidence in those with noncancerous distinct iodine-unstained lesions (DIULs; 16/268; 6.0%), esophageal SCC (9/66; 13.6%), and oropharyngolaryngeal SCC (4/19; 21.1%) than in cancer- and DIUL-free controls (24/1182; 2.0%). The presence of esophageal melanosis was associated with higher risks for noncancerous DIULs, esophageal SCC, and oropharyngolaryngeal SCC (odds ratios, 2.81, 6.54, and 14.77, respectively). Men with the inactive ALDH2*1/2*2 genotype had a higher risk for esophageal melanosis (2.66-fold), as well as for DIULs and SCCs. Conclusions. The presence of esophageal melanosis in alcoholic Japanese men could indicate a high risk for DIULs and SCCs in the upper aerodigestive tract. The high incidence of esophageal melanosis may be partially linked to high acetaldehyde exposure, a consequence of drinking alcohol in persons with inactive ALDH2. [ABSTRACT FROM AUTHOR]

Purpose: To study the recognition of malignant lesions of the liver on diffusion-weighted images (DWI) can be improved by the administration of superparamagnetic iron oxide (SPIO).Materials and Methods: Pre- and post-SPIO mediated DWI of the liver was compared in six patients with suspected malignant liver lesions at 1.5 Tesla using a parallel imaging technique.Results: Post-SPIO DWI showed improved contrast-to-noise ratio between malignant lesions and liver. Furthermore, the spleen signal was decreased on post-SPIO DWI, thus avoiding the overlap of the spleen and left lobe of the liver on maximum intensity projections (MIP).Conclusion: Recognition of malignant lesions of the liver was improved by SPIO on DWI. On MIP images of DWI, SPIO helped to decrease the overlap of spleen signal on the liver in some projection angles. [ABSTRACT FROM AUTHOR]

It has been reported that 3D-FLAIR can reduce the flow artifact resulting from cerebrospinal fluid (CSF) at 1.5 T compared to 2D-FLAIR. Flow-related artifacts tend to be worse at 3 T than at 1.5 T. The purpose of this study was to compare the CSF flow artifacts of 2D-FLAIR and 3D-FLAIR sequences at 3 T in eight healthy volunteers. The grade of CSF-related artifacts were scored through observing the perimedullary cistern, cerebellopontine angle cisterns, fourth ventricule, prepontine cistern, suprasellar cistern, ambient cisterns, sylvian fissures, third ventricle and lateral ventricles. Grading was performed on either axial or sagittal images. The CSF in-flow artifact scores were significantly higher on axial 2D-FLAIR than on axial 3D-FLAIR MPR images in all areas except the bilateral sylvian fissures, and higher on sagittal 2D-FLAIR than on sagittal 3D-FLAIR MPR images in perimedullary, bilateral CP angle and suprasellar cisterns. The CSF-related flow artifacts were significantly reduced by 3D-FLAIR, while structures in the cistern were depicted more clearly, even at 3 T. Further study is necessary to compare the clinical efficacy between 2D-FLAIR and 3D-FLAIR in depicting subtle abnormalities. [ABSTRACT FROM AUTHOR]

The article presents a study that examined a possible relationship between alcoholic chronic pancreatitis (ACP) and alcoholic liver cirrhosis (ALC). Grouping patients by endoscopic retrograde cholangiopancreatography grading and child classification revealed a nonparallel relationship between the severities of the two diseases. This relationship held, even after controlling for several pertinent background variables by logistic regression analysis. The drinking of spirits and a high daily consumption of alcohol were independent risk factors for ACP, while never-married status was the only risk factor identified with ALC among the male Japanese patients.

Functional MR imaging (fMRI) study using hyperventilation and breath-holding task has been reported to be one of the non-invasive methods to examine whole-brain vascular reactivity. The purpose of this study was to evaluate the efficacy of a method for 3D prospective detection and correction of head motion (3D-PACE) in a study of whole-brain vascular reactivity using hyperventilation and breath-holding tasks. Eight healthy volunteers were scanned using an fMRI protocol of hyperventilation and breath-holding task blocks at 3 T in separate runs with and without 3D-PACE. In two subjects, two more runs with and without 3D-PACE were repeated. The mean total number of activated voxels +/- standard deviation was 26,405.3+/-1,822.2 in the run with 3D-PACE and 17,329.9+/-2,766.3 in the run without 3D-PACE ( P<0.05), although there is some intersubject variation regarding the effect of 3D-PACE. In the two subjects whose performed two more runs, the number of activated voxels were smaller in the run without 3D-PACE than even in the run with 3D-PACE performed later. We conclude that 3D-PACE is beneficial for fMRI studies of whole-brain vascular reactivity induced by hyperventilation and breath-holding. [ABSTRACT FROM AUTHOR]

This paper presents an outline of the Japanese Society of Alcohol-Related Problems. The precursor of the Society was the Japan Alcoholism Treatment Research Group, inaugurated in 1979, by merging two local research groups in the Tokyo and Osaka areas, both of which were exclusive gatherings of psychiatrists associated with alcoholism clinics. The Research Group developed into the Society in 1992, as the number of participants including those from other medical professions increased yearly, and the subjects of the group widened to include all addictive behaviours. In reflecting the process of establishment, it is unique in many aspects as a scientific society. The Society is not a science-orientated body for presentation of new research findings. The main programme of the annual meeting is therefore a set of symposia in which members participate and discuss clinical and/or social problems arising from dependency on alcohol or drugs. Perhaps because of its content, the annual meeting is attended each year by the largest number of participants among all the societies in Japan concerned with alcohol and drugs. For the next several years, the Society's activities will be directed at (1) establishment of guidelines for early identification of and intervention in alcohol-related problems; (2) expansion of its membership to include those in related fields of medicine and non-medical professions; (3) improvement of the system of journal publication; and (4) creation of a system for timely adequate response to social problems associated with drugs and alcohol. [ABSTRACT FROM AUTHOR]

Alcohol has been known to be associated with an increased risk of cancer. We investigated the characteristics of hepatocellular carcinoma (HCC) in heavy drinkers with negative serum markers for viral hepatitis (non-B, non-C) to determine whether ethanol enhances the development of HCC in Japanese patients with or without serum markers for viral hepatitis. Among the 432 HCC cases seen at our hospital between 1995 and 2000, 26 patients had negative serum markers (non-B, non-C) and were heavy drinkers. The mean patient age at the time of HCC diagnosis was 64.2±7.6 years. The mean total ethanol intake was 1617±796 kg. Most of the patients also had liver cirrhosis (LC), although the frequency was significantly higher in non-B, non-C, heavy drinkers HCC cases than in non-B, non-C, non-alcoholic HCC cases. Among the hepatitis C virus (HCV)-positive cases, the mean age at the time of HCC diagnosis was lower in heavy drinkers; this trend was not seen in HBV-positive cases. In HCC cases with heavy drinking, a high frequency of gastrointestinal (oropharynx, esophagus, stomach, colon and anal) cancers was seen. As for the aldehyde dehydrogenase-2 (ALDH2) genotype, the frequency of normal homozygotes was 87.5% in heavy drinkers with HCC and the frequency of heterozygotes was 12.5%; the frequency of heterozygotes was 58.3% in alcoholics with esophageal cancer. More than half of the non-B, non-C, heavy drinkers HCC cases had a normal range of serum alpha-fetoprotein (AFP) levels. These results indicate that heavy drinking enhances HCV-related hepatocarcinogenesis. Whether or not ethanol is directly involved in hepatocarcinogenesis remains controversial, but LC may progress HCC in heavy drinkers even if their serum markers for HBV (including tissue) or HCV are negative. Therefore, close observation, including radiographic examinations, is recommended for non-B, non-C, heavy drinkers with LC. In HCV-positive cases, abstinence or a reduction in daily ethanol intake is recommended. [Copyright &y& Elsevier]

The purpose of this study was to optimize the parameters of diffusion-tensor magnetic resonance imaging (DT MRI) for brain fiber tracking using a slice thickness of 2 mm, a resolution advantage allowed by the high signal-to-noise ratio at 3 T, combined with an 8-channel phased-array head coil. The b-factor, number of motion probing gradient (MPG) directions, and number of averages were varied, and the results of brain fiber tracking for the pyramidal tract and trigeminal nerve were compared qualitatively and quantitatively. The DT MRI data sufficient for brain fiber tracking in healthy subjects can be obtained in <2 min with a 2-mm slice thickness, 700-s/mm2 b-factor, 6 MPG directions, and no averaging (number of averages=1). [ABSTRACT FROM AUTHOR]

Aims: Cholecystokinin (CCK), one of the most abundant neurotransmitter peptides, interacts with dopamine. Dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. CCK modulates dopamine release in the nucleus accumbens via the CCK-A receptor (R). We recently determined the transcriptional start site of the human CCK-AR gene, and detected two sequence changes (-81A/G and -128G/T) in the promoter region. The aims of the present study were to determine the prevalence of the -81A/G and -128G/T polymorphism of the CCK-AR gene between alcoholics and normal control subjects and the occurrences of the polymorphisms in subtypes of alcoholics. Methods: The above polymorphisms were examined in 435 alcoholics and 1490 control subjects. We excluded subjects with inactive ALDH2 and employed the subjects with ALDH2*1/2*1 (384 alcoholics and 792 controls). Results: The allelic frequency of -81G in the CCK-AR gene polymorphism (-81A/G) was significantly higher in alcoholics than in control subjects. However, there were no differences between the two groups with respect to the frequency of -128G/T. Alcoholic patients with antisocial personality disorder and with first-degree alcoholic relatives were significantly associated with a higher frequency of the -81G allele. In addition, the age of onset of alcohol dependence was significantly earlier in patients with this allele. Conclusions: The CCK-AR gene -81A/G polymorphism, especially in the -81G allele, may be associated with intractable alcoholism. [ABSTRACT FROM AUTHOR]

Alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) gene polymorphisms play roles in ethanol metabolism, drinking behavior and esophageal carcinogenesis in Japanese; however, the combined influence of ADH2 and ALDH2 genotypes on other aerodigestive tract cancers have not been investigated. ADH2/ALDH2 genotyping was performed on lymphocyte DNA samples from Japanese alcoholic men (526 cancer-free; 159 with solitary or multiple aerodigestive tract cancers, including 33 oropharyngolaryngeal, 112 esophageal, 38 stomach and 22 multiple primary cancers in two or three organs). After adjustment for age, drinking and smoking habits, and ADH2/ALDH2 genotypes, the presence of either ADH2*1/2*1 or ALDH2*1/2*2 significantly increased the risk for oropharyngolaryngeal cancer [odds ratios (ORs), 6.68 with ADH2*1/2*1 and 18.52 with ALDH2*1/2*2] and esophageal cancer (ORs, 2.64 and 13.50, respectively). For patients with both ADH2*1/2*1 and ALDH2*1/2*2, the risks for oropharyngolaryngeal and esophageal cancers were enhanced in a multiplicative fashion (OR = 121.77 and 40.40, respectively). A positive association with ALDH2*1/2*2 alone was observed for stomach cancer patients who also had oropharyngolaryngeal and/or esophageal cancer (OR = 110.58), but it was not observed for those with stomach cancer alone. Furthermore, in the presence of ALDH2*1/2*2, the risks for multiple intra-esophageal cancers (OR = 3.43) and for esophageal cancer with oropharyngolaryngeal and/or stomach cancer (OR = 3.95) were higher than the risks for solitary intra-esophageal cancer and for esophageal cancer alone, but these tendencies were not observed for ADH2*1/2*1 genotype. Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for oropharyngolaryngeal cancer and 63.9% for esophageal cancer. [ABSTRACT FROM PUBLISHER]

Due to a mistake of duplicating the publication of original data which already appeared in Circulation Research (84: 1073–1084, 1999), the following paper published in Molecular Cellular Biochemistry has been retracted with an apology: [ABSTRACT FROM AUTHOR]

Abstract The participation of matrix metalloproteinases (MMP) and their specific inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMP), in both the formation and degradative recovery processes of liver fibrosis were mainly reviewed from the molecular biological aspect. Since authors first reported increased activity of interstitial collagenase in the early stage of hepatic fibrosis in rats induced by chronic CCl4 intoxication, in baboons fed alcohol chronically and in patients with alcoholic fibrosis, other investigators have also demonstrated increased activity biologically and histochemically. However, species-specific differences in response have been found and gene-level research on the rat model has not demonstrated increased mRNA transcription of collagenase. It has also been clarified that activated stellate cells can also produce matrix components. Very recently, authors observed the participation of interstitial collagenase in the recovery from experimental hepatic fibrosis by using polymerase chain reaction northern blotting and in situ hybridization. The in situ hybridization findings not only demonstrated the cells responsible for interstitial collagenase, but also suggested a great deal about the mechanism of recovery from fibrosis. Hepatic stellate cells are activated via the expression of c-myb and nuclear factor-κB (NFκB) which is induced by oxidative stress, and inhibited by antioxidant (1-α-tocopherol) and butylated hydroxytoluene. The activation mechanism is now being revealed. The relationship between the activation mechanism of stellate cells and the production and secretion of MMP and TIMP in the formation and recovery process of hepatic fibrosis should be investigated from the promoter gene level. This approach might help develop a new strategy for the treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]