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Biomedical subjects

H W Goedde

Publications and source records attributed to H W Goedde.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacogenetics of alcohol metabolism and alcoholism.

The pharmacogenetic differences among individuals in their capacity to metabolize ingested alcohol are possibly responsible for the large inter-individual and inter-ethnic variations observed in the outcome of alcohol use and misuse. Based on results of adoption, twin, and family studies it is now widely accepted that the vulnerability to alcoholism is determined by genetic factors as well as by environment. There is a constant search for biological markers and specific genes which could identify individuals genetically predisposed to alcohol abuse and alcoholism. Numerous 'candidate genes' for alcoholism have been suggested including the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both ADH and ALDH exhibit genetic heterogeneity. An atypical form of ADH (ADH2), which contains a variant beta 2 subunit instead of the usual beta 1 subunit, differs substantially from the usual form in its kinetic properties and is found more frequently among the Japanese, Chinese and other Mongoloid populations than in Caucasoids and Negroids. A widely prevalent genetic polymorphism has been observed for ALDH; about 50% of Japanese and Chinese livers possess an inactive ALDH (ALDH2 isozyme) whereas none of the Caucasian or Negroid populations show this isozyme abnormality. These metabolic polymorphisms seem to contribute to differences in the in vivo elimination rate of ethanol and acetaldehyde, and may explain differences in alcohol-related behaviour and its disease outcome. Taken together, Orientals who possess an atypical ALDH2 gene are more sensitive to acute responses to alcohol, tend to be discouraged from drinking alcohol, and consequently are at lower risk of developing alcohol-related disorders. However, more work is needed to support these findings. Recent advances in molecular genetics have made it possible to analyze directly the human genome. This may help in a better understanding of the complex genetic and environmental factors in alcohol abuse by providing prospects for identification of gene loci which may be responsible for predisposition to, and protection from, alcoholism.

Alcohol Dehydrogenase↗
PubMed1979

[Ecogenetics].

Some examples of ecogenetics--including pharmacogenetics--demonstrate the tremendous variability in genetic constitution within a population as well as between different populations. They are the reason for different atypical responses to xenobiotics, synthetics like drugs, pesticides, insecticides, herbicides, industrial irritation, smog, cigarettes, alcohol, as well as naturally occurring substances like aflatoxines. It is unknown to what extent individuals differ in their susceptibilities and which genetic consequences of exposure of the human population to toxic environmental agents will occur. It is referred to genetic traits causing a predisposition for atypical reactions against chemicals of different structure as well as to the mutagenic and inductive action of such compounds. In this connection, population genetic aspects will be considered. All examples have to be seen in the context of ecogenetics, the genetically determined individual differences in adverse responses to environmental pollutants, and they are of special interest for preventive and industrial medicine.

Carboxylic Ester Hydrolases↗
PubMed1979

Diurnal rhythm in the plasma level of total and free tryptophan and cortisol in rabbits. Effect of haloperidol and chlorpromazine.

Plasma tryptophan level varied diurnally with highest concentrations at 12 noon (P less than 0.001); at that time free tryptophan level was lowest. The mean 8 h and 16 h cortisol levels were 70% higher compared to levels obtained at 24 h. Chronic administration of haloperidol and chlorpromazine led to significant increase in the plasma tryptophan (P less than 0.001 and P less than 0.1, respectively) compared to saline-treated rabbits. This change was associated with corresponding constant or reduced free tryptophan levels, and a diminution in plasma cortisol level (10 microgram/l) compared with controls (34 microgram/l). The results suggest that tryptophan in plasma is poorly transported in the brains of rabbits treated with chlorpromazine, and that treatment with haloperidol or chlorpromazine may lead to a reduced tryptophan flux into the kynurenine pathway.

Animals↗
PubMed1979

Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts.

Rapid and sensitive micromethods for the study of alcohol dehydrogenase and adehyde dehydrogenase isozymes in skin extracts, cultured fibroblasts and other organs are presented. Possibilities for the application of these techniques to the study of interindividual variations in response to alcohol are discussed. While fibroblasts cultured from a skin biopsy from one Japanese individual revealed a heterodimer (ADH2 2-1) of alcohol dehydrogenase, skin extract from another Japanese showed a homodimer (ADH2 2-2). Up to four isozyme sets for aldehyde dehydrogenase (ALDH) were detected in various human organs and at least three sets were found in skin and fibroblasts extracts. Our preliminary data on liver, stomach, and skin indicate that ALDH is polymorphic and several loci are concerned in the determination of these isozyme sets.

Alcohol Oxidoreductases↗
PubMed1979

Monoamine oxidase and catechol-o-methyltransferase activity in cultured fibroblasts from patients with maple syrup urine disease, Lesch-Nyhan syndrome and healthy controls.

Monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT) activities have been measured in fibroblasts from nine healthy controls, three patients with maple syrup urine disease (MSUD) and six patients with Lesch-Nyhan syndrome. Both A and B types of MAO activity are found in these cell lines. In comparison to controls, the MAO activity is significantly reduced in cells from patients with Lesch-Nyhan syndrome. A different situation has been observed in the cell lines from MSUD patients: one showed a high MAO activity, another a significantly reduced activity, and the third was in the range of the normal controls. COMT activity is also present in these cells, but with a wide variation. No specific differences have been noted among the controls and the mutant cells.

Catechol O-Methyltransferase↗
PubMed1978

Isozyme variations in acetaldehyde dehydrogenase (e.c.1.2.1.3) in human tissues.

NAD-dependent acetaldehyde dehydrogenase (ALDH) of human tissues was investigated by electrophoresis and enzyme assay. ALDH is located mainly in the liver and kidney. The isozymes consist of at least six different components. Five different phenotypes were found in a total of 68 human liver and kidney specimens. It is likely that three isozyme sets are concerned in determining ALDH types. The distribution of various phenotypes of ALDH isozyme sets is presented.

Aldehyde Oxidoreductases↗
PubMed1978

[Liver disease in homozygous alpha1-antitrypsin deficiency (author's transl)].

Among twelve patients with homozygous alpha1-antitrypsin deficiency (Pi-type Z), five cases of infantile liver disease were diagnosed. The course of the disease was extremely variable; only one patient died of liver cirrhosis at the age of fourteen. In four cases the clinical, biochemical and histological (2 cases) findings became normal over a follow-up period of one to fifteen years. The results of these observations demonstrate that in alpha1-antitrypsin deficiency even when associated with proven liver disease the prognosis need not be unfavorable.

Adolescent↗
PubMed1978

Human liver alcohol dehydrogenase isoenzyme variations. Improved separation methods using prolonged high voltage starch-gel electrophoresis and isoelectric focusing.

Human liver alcohol dehydrogenase isozyme patterns were studied using prolonged high voltage starch-gel electrophoresis and gel-slab isoelectric focusing. Homo- and heterodimers of ADH2 locus were easily distinguished from each other. The gene frequencies of ADH2 2 and ADH2 3 in 46 random liver samples from Germany were found to be 0.044 and 0.424 respectively.

Alcohol Oxidoreductases↗
PubMed1978

Creatine kinase isoenzyme patterns in Duchenne muscular dystrophy.

Serum creatine kinase isoenzymes were studied in 41 patients suffering from Duchenne type muscular dystrophy and 20 mothers of patients (carriers) by cellulose acetate electrophoresis. Both the MM and MB types were found in all cases of Duchenne type dystrophy patients, and in carriers with highly elevated total creatine kinase activity BB was not observed above the detection limits of the methods used. However, a so-called atypical CK--BB band has been demonstrated.

Creatine Kinase↗