K Kuriyama, H Mizutani, M Hirouchi, T Ichida, T Hashimoto
{"title":"Alteration in cerebral GABAB receptor functions during formation of alcohol dependence.","authors":"K Kuriyama, H Mizutani, M Hirouchi, T Ichida, T Hashimoto","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alterations in the function of cerebral GABAB receptor systems were studied in alcohol dependent animals and reconstituted GABAB receptor systems in vitro. The GABAB receptor binding at both high and low affinity sites showed a significant increase during the formation of alcohol dependence and alcohol withdrawal, although ethanol at a low concentration did not affect the GABAB receptor binding in vitro. On the other hand, a low concentration (100 mM) of ethanol, which had no significant effect on GABAB receptor binding, inhibited cAMP accumulation in vitro. The cAMP formation in brain did not show significant changes during the formation of alcohol dependence in spite of the increase in GABAB receptor binding. These results indicate that alcohol dependence induces an increase of GABAB receptor binding in the brain. This increase in GABAB receptor binding, however, may not be associated with the changes in the GABAB receptor mediated suppression of cAMP formation, possibly due to the deterioration of the coupling between the GABAB receptor and the Gi/Go type of GTP binding protein/adenylyl cyclase. Furthermore, the present results suggest that in vitro addition of ethanol may have differential effects on cerebral GABAB receptor systems as compared with those found in the brain of alcohol dependent subjects.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"2 ","pages":"193-7"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19937915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aldehyde dehydrogenase and acetaldehyde metabolism.","authors":"H Weiner, X Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Ingested ethanol is first oxidized to acetaldehyde, primarily in the liver, then further oxidized to acetate. The oxidation of acetaldehyde is catalyzed by an NAD-dependent aldehyde dehydrogenase located in the liver mitochondrial matrix space. To date only one variant form of aldehyde dehydrogenase has been identified. Many Oriental people have an inactive mitochondrial form which possesses a lysine residue at position 487 rather than glutamate which is found in the active enzyme. We employed site directed mutagenesis to probe for active site residues in the enzyme and identified a number of residues which, if mutated, would produce an impaired or inactive enzyme. These mutations could be obtained by single base changes in the DNA coding for the enzyme. Though not identified in human populations, it is possible that these null mutants of the enzyme could exist in people deficient in active mitochondrial aldehyde dehydrogenase.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"2 ","pages":"141-5"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19935918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mammalian aldehyde dehydrogenases: regulation of gene expression.","authors":"R Lindahl","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The mammalian aldehyde dehydrogenases (ALDH) are a family of functionally and structurally related enzymes encoded by multiple genes. Genes representing each major class of mammalian ALDHs, Class 1, 2 and 3, have been cloned and characterized. Functional analysis of the 5' flanking regions of these genes is just beginning, but such studies suggest roles for a diverse set of cis-elements and trans-acting factors in the tissue-specific and ligand-mediated expression of the ALDH genes.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"2 ","pages":"147-54"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19935919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chronic alcoholics have substantial glial pathology in the forebrain and diencephalon.","authors":"K M Cullen, G M Halliday","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have analyzed glial changes in forebrain and diencephalic regions in 19 alcoholics with different histories of chronic alcohol consumption and related medical complications including Wernicke's encephalopathy and alcoholic liver disease. Cases with postmortem evidence of hepatic encephalopathy were excluded. Two of the alcoholic patients had ceased drinking for several years prior to death. Brains were obtained postmortem and fixed in formalin. Serial 50 microns sections of the forebrain and diencephalon at 750 microns intervals were stained with standard histochemical stains (haematoxylin and eosin, luxol fast blue, cresyl violet and silver), as well as immunohistochemically for glial fibrillary acidic protein (GFAP). In control tissue, GFAP-positive astrocytes were intimately associated with ependymal, pial, and vascular surfaces. In alcoholic cases, the morphology of these cells was markedly changed showing enlargement of the cell bodies and beading of the cellular processes. In contrast to controls, GFAP-positive astrocytes were seen within and surrounding clusters of magnocellular neurons in the basal forebrain and hypothalamus. In thiamine-deficient alcoholics, glial scarring in the vicinity of the large branches of the cerebral arteries disrupted the normal forebrain architecture. A patchy loss of GFAP immunostaining was seen in most severe cases. A remarkable number of corpora amylacea also rimmed blood vessels, pial and ependymal surfaces in all alcoholics compared to controls. The beaded fibers were seen in alcoholics drinking at the time of death as well as in those who had ceased drinking alcohol several years prior to death. These results indicate that chronic alcoholics have prominent glial changes which persist despite the cessation of alcohol consumption and are not exclusive to alcoholics with liver pathology.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"2 ","pages":"253-7"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19936432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P R Martin, S R Pekovich, B A McCool, W O Whetsell, C K Singleton
{"title":"Thiamine utilization in the pathogenesis of alcohol-induced brain damage.","authors":"P R Martin, S R Pekovich, B A McCool, W O Whetsell, C K Singleton","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>There is increasing evidence for the role of thiamine deficiency in ethanol neurotoxicity and in development of alcoholic organic brain disorders other than Wernicke-Korsakoff syndrome [WKS] and cerebellar degeneration. Investigations in humans and in animal models have implicated a reduction in the activities of thiamine-utilizing enzymes as the metabolic basis of tissue injury due to thiamine deficiency. We have investigated the interactions of the thiamine-utilizing enzyme transketolase [Tk], derived from human fibroblasts, lymphoblasts, and various brain regions, with its cofactor, thiamine pyrophosphate [TPP], in an attempt to elucidate the molecular basis of selective brain damage in alcoholism-associated thiamine deficiency. There were no significant differences in the isoelectric pattern of Tk among the nine brain regions (white matter and grey matter) examined. However, Tk activity/mg protein, increase in Tk activity with addition of excess TPP (TPP effect), and TPP-dependent rate of formation of active Tk holoenzyme (tau) varied 2.5-, 6-, and 4-fold, respectively, among these brain regions. These differences in tissue requirements for TPP may contribute to the selective vulnerability of certain brain regions to alcoholism-associated thiamine deficiency, and may influence the pattern of clinical impairment in the individual patient.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"2 ","pages":"273-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19936435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Oshita, Y Takei, S Kawano, T Hijioka, H Fusamoto, T Kamada
{"title":"Alcohol and endogenous nitric oxide in hepatic microcirculation.","authors":"M Oshita, Y Takei, S Kawano, T Hijioka, H Fusamoto, T Kamada","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study investigated the role of endogenous nitric oxide in the regulation of hepatic vascular tone in the presence of ethanol. In the perfused rat liver, upon the initiation of ethanol infusion into the liver, portal pressure was increased in a dose-dependent manner, reaching maximal levels in 2-5 min, then decreasing gradually. Simultaneous infusion of N(G)-monomethy 1-L-arginine, a nitric oxide synthesis inhibitor, enhanced this ethanol-induced increase in portal pressure. This enhancement was reversed by simultaneous infusion of a precursor of nitric oxide, L-arginine. These results suggest that endogenous nitric oxide acts as a vasodilator which reduces ethanol-induced vasoconstriction, thus improving the perturbation of hepatic microcirculation by ethanol.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"29 1","pages":"5-7"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20020414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Experimental study of the reversibility of sinusoidal capillarization.","authors":"T Mori, T Okanoue, H Kanaoka, Y Sawa, K Kashima","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study investigated the reversibility of sinusoidal capillarization in fibrotic rat liver induced by thioacetamide (TAA; 200 mg/kg body weight three times a week). Six weeks later, collagen fibers and hepatic lobular disarrangement were observed on light microscopy and basement membrane formation was noted in the space of Disse. Sinusoidal endothelial fenestrations (SEFs) were decreased in size and number (defenestration), and factor VIII-related antigen was observed in the cytoplasm. We also clarified the phenotypic reversibility of the sinusoidal endothelial cells. After 4 months following discontinuation of TAA exposure, the diameters and numbers of SEFs were increased. Six months later, the basement membrane in the space of Disse disappeared (as assessed by electron microscopy) and 12 months later, factor VIII-related antigen also disappeared. These results indicate that phenotypical changes in the sinusoidal endothelial cells and sinusoidal capillarization in hepatic fibrosis may be reversed.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"29 1","pages":"67-74"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20020417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Ishii, S Furudera, R Kumashiro, J Seo, Y Koga, M Sata, K Tanikawa
{"title":"Role of serum interleukin-8 and intercellular adhesion molecule-1 in the severity of alcoholic hepatitis.","authors":"K Ishii, S Furudera, R Kumashiro, J Seo, Y Koga, M Sata, K Tanikawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Among patients with alcoholic hepatitis, three groups were distinguished by histological findings and clinico-pathological features. The aim of this study was to clarify the role of soluble intercellular adhesion molecule-1 (sICAM-1) and interleukin-8 (IL-8) in the development of severe alcoholic hepatitis. The levels of sICAM-1 and IL-8 were well correlated with the severity of liver injuries. The concentrations of serum IL-8 were significantly correlated with the number of polymorphonuclear leukocytes infiltrating the liver. Serial determination of these two markers revealed that IL-8 may be complementary in assessing the severity and prognosis of alcoholic hepatitis.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"29 1","pages":"81-5"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20020419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A Shibuya, A Takeuchi, H Shibata, K Saigenji, A Yoshida
{"title":"Immunohistochemical study of hepatocellular carcinoma-specific aldehyde dehydrogenase.","authors":"A Shibuya, A Takeuchi, H Shibata, K Saigenji, A Yoshida","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tumor-associated aldehyde dehydrogenase (ALDH) was reported in cases of human hepatocellular carcinoma and animal hepatoma models. This ALDH isozyme is similar to ALDH3 which exists in the stomach and lung; however, the biochemical and clinical significance of this unique ALDH isozyme have not been established. Human tumor-associated ALDH was purified, and polyclonal antibodies prepared. Using these antibodies, specific development of tumor-associated ALDH was confirmed by immunohistochemical techniques. It was found that about 50% of hepatocellular carcinomas reacted with the antibody. This unique ALDH isozyme may be a novel tumor marker of hepatocellular carcinoma.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"29 1","pages":"119-23"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20021095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A study on ADH2 and ALDH2 genotyping by PCR-RFLP and SSCP analyses with description of allele and genotype frequencies in Japanese, Finn and Lapp populations.","authors":"K Suzuki, A Uchida, Y Mizoi, T Fukunaga","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genetic polymorphisms of the alcohol dehydrogenase ADH2 and aldehyde dehydrogenase ALDH2 genes were investigated in Japanese, Finn, and Lapp populations by using PCR-RFLP and SSCP analyses. The ALDH2 genotypes were unequivocally determined by a PCR-RFLP assay with a mismatched primer. The determination of the ADH2 genotypes, however, was found to be problematic in PCR with the reported oligonucleotide primer sets because there are high homologies among the ADHl, ADH2, and ADH3 gene sequences. The problem of the heterozygote excess in typing results obtained by using the previously reported PCR-RFLP methods was resolved by nested PCR, in which an internal primer set reamplified the ADH2 sequence selectively from a mixture of the ADH gene sequences amplified in the first PCR amplification of genomic DNA samples as templates. A newly designed primer pair with longer sequences and single 3' end mismatches was later found to achieve a predominant amplification of the ADH2 sequence in a single PCR. RFLP and SSCP analyses of PCR products with the new primer set gave results fully consistent with those by nested PCR. Thus, the ADH2 genotypes defined in this study were free from any typing errors. The ADH2 and ALDH2 allele frequencies observed in this study were found not to be biased significantly from those reported previously from Japanese populations, and these were monomorphic for Lapp and Finn populations.</p>","PeriodicalId":7689,"journal":{"name":"Alcohol and alcoholism (Oxford, Oxfordshire). Supplement","volume":"29 1","pages":"21-7"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20021101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}