Search PubMed⌕ Search

Biomedical subjects

H W Goedde

Publications and source records attributed to H W Goedde.

At least 55 records · Page 3Linked to original sources
PubMed1989

[New aspects of acetaldehyde metabolism in human tissues and erythrocytes].

Acetaldehyde, the active metabolite of ethanol oxidation, has been implicated to be mainly responsible for the diverse toxic effects of alcohol drinking. Aldehyde dehydrogenase (ALDH) catalyzes the oxidation of acetaldehyde in human liver and other organs. Impaired acetaldehyde metabolism by way of reduced ALDH activity may be the primary cause of tissue injury. Erythrocyte ALDH activity has been found to be decreased in alcoholics and returns to normal values on reducing the alcohol intake. The purpose of this study was to determine the interindividual variation in ALDH activity in different human tissues and erythrocytes. Results of the present study show that significant interindividual variation occurs in ALDH activity in different tissues. This variability in ALDH activity might explain the widely observed interindividual and ethnic/racial differences in alcohol intolerance and susceptibility to ethanol- and acetaldehyde-related tissue and organ damage. The study also confirms earlier observations that erythrocyte ALDH activity significantly varies in healthy individuals without alcohol abuse. This fact should be taken into consideration while evaluating the erythrocyte ALDH activity as a potential marker of alcoholism.

Acetaldehyde↗
PubMed1988

Alkali myosin light chains in man are encoded by a multigene family that includes the adult skeletal muscle, the embryonic or atrial, and nonsarcomeric isoforms.

A set of cDNA clones coding for alkali myosin light chains (AMLC) was isolated from fetal human skeletal muscle. Nucleotide sequence analysis and RNA expression patterns of individual clones revealed related sequences corresponding to (i) fast fiber type MLC1 and MLC3; (ii) the embryonic MLC that is also expressed in fetal ventricle and adult atrium (MLCemb); and (iii) a nonsarcomeric MLC isoform that is found in all nonmuscle cell types and smooth muscle. The AMLC gene family in man comprises unique copies for MLC1, MLC3 and MLCemb, and multiple copies for the nonsarcomeric MLC genes. The gene coding for MLC1 and MLC3 is located on human chromosome 2.

Amino Acid Sequence↗
PubMed1987

Liver glutathione S-transferase polymorphism in Japanese and its pharmacogenetic importance.

A total of 168 autopsy liver extracts from Japanese individuals were examined for the glutathione S-transferase (GST) isozymes by means of starch gel electrophoresis. The gene frequencies of GST1*1, GST1*2, and GST1*0 in Japanese were 0.252, 0.057, and 0.691, respectively. GST1*3 was detected as a rare variant allele. The incidence of GST1 0 in 41 liver biopsy samples from patients suffering from various liver diseases was investigated using polyacrylamide gel isoelectric focusing. The GST1 0 phenotype was found more frequently in livers with hepatitis and carcinoma than in control livers. The isozymes coded by different GST loci were partially purified and characterized to study their biochemical properties. The apparent Km values with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate for the isozymes at the GST1, GST2, GST3, and GST4 loci were 604, 1345, 776, and 591 microM, respectively.

Alleles↗
PubMed1987

Distribution of alpha-1-antitrypsin and haptoglobin phenotypes in bladder cancer patients.

Frequencies of the alpha 1-antitrypsin (Pi) alleles and haptoglobin phenotypes have been determined in a series of 264 North-German patients with bladder cancer. Compared to a healthy control population, we found a statistically significant decrease of Hp 2-2 phenotype in the patient series. A significant increase of the serum Pi Z allele, as previously shown for patient groups with certain other tumours, could also be confirmed for bladder cancer. Furthermore, a distinct association between a lowered M 3 allele and bladder carcinoma was observed.

Alleles↗
PubMed1987

Polymorphism of aldehyde dehydrogenase and alcohol sensitivity.

The metabolism of acetaldehyde has received considerable attention in the past years owing to its acute and chronic toxic effects in humans. Aldehyde dehydrogenase (ALDH) catalyzes the oxidation of acetaldehyde in liver and other organs. Two major isozymes of hepatic ALDH (ALDH I or E2 and ALDH II or E1), which differ in their structural and functional properties, have been characterized in humans. The ALDH I with a low Km for acetaldehyde is predominantly of mitochondrial origin and ALDH II which has a relatively higher Km is of cytosolic origin. An inherited deficiency of ALDH I isozyme has been found among Japanese and Chinese which is primarily responsible for producing acute alcohol sensitivity symptoms (flushing response) after drinking mild doses of alcohol. Biochemical, immunochemical and molecular genetics data indicate a structural mutation in the ALDH I isozyme gene responsible for the loss in catalytic activity. Population genetic studies indicate a wide prevalence of this ALDH polymorphism among individuals of Mongoloid race. Flushing response to alcohol shows familial resemblances and preliminary family data from Japan, China and Korea hint to an autosomal codominant inheritance for ALDH I isozyme deficiency. The ALDH polymorphism is apparently responsible for the low incidence of alcoholism in Japanese, Chinese and Koreans. Alcohol-induced sensitivity due to ALDH isozyme deficiency may act as an inhibitory factor against excessive alcohol drinking thereby imparting a protection against alcoholism.

Alcohol Drinking↗
PubMed1987

Genetic markers among three population groups of Hungary.

Three ethnic groups from Hungary, the general population of Hungary, the Matyo and the Gypsies, were examined with respect to the genetic markers PGP, GLO1, GPT, ACP1, ESD, PGD, ADA, AK1, PGM1 subtypes, C3, BF, HP, GC subtypes, PI, TF subtypes and AMY2. Significant variations were noted for the gene frequencies of GPT and PGD between the Hungarian and Matyo sample. The Gypsies deviate in the systems of GLO1, ACP1, ADA, C3, BF and HP from the Hungarians.

Adult↗
PubMed1987

Red cell and serum protein polymorphisms in three population groups of South Korea.

Genetic markers ACP1, PGM1 with subtypes, ESD, GLO1, PGD, GPT, PGP, C3, TF and GC with subtypes, BF, HP, AMY, PLG and PI, were studied in three populations in South Korea, one being the population of the industrial capital Seoul, the second a rural group from Taejon and the third the population of Cheju Island. For the polymorphic systems studied in the present work, a general similarity was observed among the three populations, with the exception of GPT and ACP1 (Taejon vs. Seoul) and subtypes of GC (Taejon vs. Cheiu).

Blood Proteins↗
PubMed1987

Human mitochondrial aldehyde dehydrogenase: mRNA expression in different tissues using a specific probe isolated from a cDNA expression library.

Using monospecific antibodies against mitochondrial aldehyde dehydrogenase (ALDH I), cDNA clones were isolated from a human liver cDNA library constructed in the plasmid expression vector pEX. Two overlapping clones pEXAL21 and pEXAL43 containing inserts of 861 bp and 1180 bp respectively, code for the carboxy-terminal end of ALDH I as confirmed by sequence analysis. The messenger RNA of ALDH I was estimated by Northern blot analysis to contain approximately 2350 nucleotides. RNA hybridizations revealed that the ALDH I gene transcription is generally low in fetal tissues. Especially, transcription in the adult liver is up to 5-fold higher than in the fetal liver.

Adult↗
PubMed1987

Aldehyde dehydrogenase polymorphism: molecular basis and phenotypic relationship to alcohol sensitivity.

Individual differences in response to alcohol have been observed in various ethnic and racial groups. A positive correlation between alcohol sensitivity and elevated blood acetaldehyde level in conjunction with deficiency of an isozyme of aldehyde dehydrogenase (ALDH I) was noted in Japanese subjects given an acute dose of alcohol. Invariably, significantly higher blood acetaldehyde levels were measured in ALDH I-deficient subjects after ethanol loading. The initial flushing in Orientals after alcohol ingestion might be due to their inability to metabolize acetaldehyde quickly and effectively in the absence of the low Km ALDH I isozyme. While Oriental populations of Mongoloid origin showed varying degree of isozyme deficiency, none of the Caucasian or Negroid populations have this isozyme abnormality.

Alcohol Drinking↗
PubMed1987

Human aldehyde dehydrogenase isozymes and alcohol sensitivity.

The metabolism of acetaldehyde has received considerable attention in the past owing to its acute and chronic toxic effects in humans. Two major hepatic ALDH isozymes, ALDH I and ALDH II, differing in their structural and functional properties, have been characterized in humans. ALDH I has a low Km for acetaldehyde and is primarily a mitochondrial enzyme, while ALDH II has a higher Km and is of cytosolic origin. An inherited deficiency of ALDH I isozyme found only among Oriental populations is primarily responsible for producing acute alcohol sensitivity symptoms (flushing response) after consumption of small doses of alcohol. Biochemical, immunochemical, and molecular genetics data indicate a structural mutation in the ALDH I isozyme gene responsible for the loss in catalytic activity. Population genetic studies have revealed the prevalence of ALDH polymorphism among individuals of the Mongoloid race. Flushing response to alcohol is a familial trait, and preliminary family data from Japan, China, and Korea suggest an autosomal codominant inheritance for ALDH I isozyme deficiency. The ALDH polymorphism is apparently responsible for the low incidence of alcoholism in Japanese, Chinese, and Koreans. Alcohol sensitivity due to ALDH I isozyme deficiency may inhibit excessive alcohol drinking.

Alcohol Drinking↗