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Susumu Higuchi

Publications and source records attributed to Susumu Higuchi.

47 records · Page 3Linked to original sources
PubMed2003

Spirits and gastrectomy increase risk for chronic pancreatitis in Japanese male alcoholics.

INTRODUCTION: Most cases of chronic pancreatitis are alcohol-related, but not all alcoholics develop pancreatitis. AIM: To elucidate historical and biologic risk factors for this disease. METHODOLOGY: Alcoholic Japanese men (n = 132) consecutively admitted to the National Alcoholism Center over 24 months, including 54 with chronic pancreatitis (diagnosed by endoscopic retrograde cholangiopancreatography) and 78 without, were surveyed about drinking history, smoking, education, and marital status, and tested for amylase, glycosylated hemoglobin, body mass, alcohol and aldehyde dehydrogenase genotypes, and K-ras gene mutations in pancreatic juice. RESULTS: Higher risk for chronic pancreatitis was associated with drinking spirits rather than lower-alcohol beverages (odds ratio [OR], 2.58; p= 0.01). Daily ethanol consumption by those who drank spirits was greater than that among those who drank lower-alcohol beverages; however, no differences in either daily ethanol consumption or duration of drinking were observed between alcoholics with and without chronic pancreatitis. Postgastrectomy patients were at higher risk for chronic pancreatitis than unoperated comparison subjects (OR, 4.35, P< 0.05). Elevated glycosylated hemoglobin (OR, 4.62, p< 0.01), decreased amylase (OR 4.20, P<0.02), and low body mass (OR 1.89, P<0.1) were more frequent in alcoholics with chronic pancreatitis. K- gene mutations existed in 18.8% of alcoholics with chronic pancreatitis but in only 11.4% of those without the disorder. The frequencies of alcohol and aldehyde dehydrogenase genotypes in alcoholics with and without pancreatitis did not differ significantly. CONCLUSION: Our study strongly suggested that spirits and partial gastrectomy increase the risk for chronic pancreatitis in male alcoholics.

Adult↗
PubMed2003

Association analyses between polymorphisms of the phase II detoxification enzymes (GSTM1, NQO1, NQO2) and alcohol withdrawal symptoms.

BACKGROUND: NRH-quinone oxidoreductase 2 (NQO2) along with glutathione S-transferase M1 (GSTM1) and NAD(P)H-quinone oxidoreductase 1 (NQO1), which is involved in phase II detoxification reactions, is thought to be important for detoxification of catechol o-quinones in the central nervous system. Our previous study revealed that the human NQO2 gene is highly polymorphic. In this study, we investigated a possible association between polymorphisms of the GSTM1, NQO1, and NQO2 genes and alcohol withdrawal symptoms such as delirium tremens, hallucination, and seizure. METHODS: A total of 247 Japanese male alcoholic patients with alcohol withdrawal symptoms or without the symptoms, and 134 age-matched Japanese male controls (nonhabitual drinkers), were examined by using polymerase chain reaction (PCR), PCR restriction fragment length polymorphism, PCR-based single-strand conformational change polymorphism, and PCR direct sequencing analyses. RESULTS A significant difference was found between alcoholic patients and controls in genotype frequency at an insertion/deletion site in the promoter region of the NQO2 gene (p = 0.0014). The frequency of the homozygous genotype for the D allele at this locus was significantly higher in delirium tremens-positive patients (p = 0.0004) and in hallucination-positive patients (p = 0.0001), and in patients displaying both delirium tremens and hallucination (p = 0.0002), than in controls. The values were still significant after Bonferroni correction. On the other hand, no significant difference was detected for allele frequencies or genotype frequencies for the other polymorphic loci of the NQO2 gene. Moreover, GSTM1 gene deletion and missense mutation (Pro187Ser) of the NQO1 gene showed no significant association with alcohol withdrawal symptoms. CONCLUSION: Present data suggest that an insertion/deletion polymorphism in the promoter region of the NQO2 gene plays an important role in the pathogenesis of alcoholism and alcohol withdrawal symptoms.

Adult↗
PubMed2002

Clinical and biomarker investigation of a patient with a novel presenilin-1 mutation (A431V) in the mild cognitive impairment stage of Alzheimer's disease.

We report an individual who developed Alzheimer's disease (AD) due to a novel presenilin-1 mutation (Alanine-->Valine at codon 431). When he first presented, the patient met criteria for mild cognitive impairment but progressed over 16 months to fulfill diagnostic criteria of AD. At his first presentation, he showed widespread metabolic deficits in the posterior cingulate, lateral parietal, posterior parietal, and medial temporal regions on positron emission tomography as well as elevated tau and phospho-tau levels in cerebrospinal fluid (CSF). We suggest that functional neuroimaging and CSF biomarkers can serve as useful predictors of development of AD. Accumulation of pathologic tau isoforms and neuron death occur even in the mildest clinical stages of AD.

Alzheimer Disease↗
PubMed2002

A clinical and neuropathological study of an unusual case of sporadic tauopathy. A variant of corticobasal degeneration?

We report a sporadic case of tauopathy with unusual clinical and neuropathological features. The patient presented with progressive symmetric rigid-akinetic parkinsonism and dementia of the subcortical type. Magnetic resonance imaging of the brain revealed atrophy resembling multiple system atrophy. The level of cerebrospinal fluid tau protein phosphorylated at serine 199 was markedly elevated. The autopsy revealed more glial than neuronal tauopathy, with much heavier involvement of subcortical white matter and the brainstem than of the cerebral cortex. Analysis of dephosphorylated tau revealed that hyperphosphorylated four-repeat tau isoforms were deposited in the brain of the patient. Despite morphological and biochemical resemblance to a certain form of familial fronto-temporal dementia, no mutation of the tau gene including exon 10 could be found. Our findings, taken together with those in previous similar case reports, indicate that the case represents an atypical form of corticobasal degeneration or a new variant of sporadic tauopathy.

Aged↗
PubMed2002

Investigation of quantitative trait loci in the CCKAR gene with susceptibility to alcoholism.

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.

Adult↗
PubMed2002

[A cohort study of Japanese adolescent alcohol use and misuse (1): Observation for 2 years].

Japanese adolescent drinking has increased during the past 20 years. Two national surveys on adolescent drinking problems were conducted, but no prospective study has been performed in Japan. We started the first longitudinal cohort study on Japanese adolescent alcohol use and misuse in 1997. The purpose of the cohort study was to show factors that promote adolescent drinking, and whether adolescent problem drinkers will develop the early alcohol dependence syndrome. Eight hundred and two subjects were recruited from four junior high schools in Kanagawa prefecture. They were in grades 7 to 9, and the mean age was 13.5 years in 1997. The survey was conducted annually by mail using self reported questionnaires concerning adolescent drinking and alcohol-related problems. This report indicates the sociodemographic backgrounds of the subjects and showed increasing of drinking of the subjects from 1997 to 1999. At 1999 survey from 2 years after the starting point, the respondents numbered 629, and the follow-up rate was 78%. Drinking frequencies and quantities of the subjects increased year by year, and alcohol-related problems also increased. We divided the subjects into two groups based on changes in drinking status from the 1997 to the 1999 survey, the increased drinking group and no increased group, and compared these two groups concerning their family relationships, first drinking age and drinking status of parents with the responses of the 1997 survey. In the comparison of the two groups, many factors were significantly different, and logistic regression analyses were performed on these factors to determine drink promoting factors. Three factors were determined: earlier age of the first drink, not refusing friends' temptations to drink and less communication with their parents. We will continue the longitudinal cohort study to determine if these three factors promote adolescent drinking in the future.

Adolescent↗
PubMedDate not supplied

Association of cholecystokinin-A receptor gene polymorphism with alcohol dependence in a Japanese population.

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.

Adult↗