Albert Iron

Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms.

Abstract In this study the GSTμ phenotype and ADH genotype at the ADH3 locus were investigated in a group of 39 alcoholic men with upper respiratory/digestive tract cancer: 21 with oropharyngeal cancer and 18 with laryngeal cancer. The results are compared with those of a control group of 37 alcoholic men without alcohol-related medical complications. Of the control subjects, 48% were found to be GSTμ deficient [GSTμ(–)] and 19% carried the ADH31/ADH31 genotype. In the laryngeal cancer patients, a significantly elevated frequency of both the GSTμ(–) (78%) and ADH31/ADH31 genotype (56%) was observed, relative to the control group. On the basis of this result, the risk of laryngeal cancer associated with the GSTμ(–) and ADH31/ ADH31 genotypic combination within the population of alcoholics was estimated to be 12.9 with a 95% confidence interval of 1.8–92 (P < 0.01) relative to alcoholic individuals who have GSTμ [GSTμ(+)] and are not ADH31/ADH31. Thus, alcoholics who are GSTμ(–) and ADH31/ADH31 have at least an 80% greater risk of developing laryngeal cancer than alcoholics who are GSTμ(+) and who are not ADH31/ ADH31. In addition, the oropharyngeal cancer patients had excess frequencies of both GSTμ(–) (62%) and ADH31/ ADH31 (43%) relative to the control group, but these excess frequencies were not statistically significant. The GSTμ(–) and ADH31/ADH31 genotypic combination may be a constitutional risk factor for laryngeal cancer among alcoholics.

Glutathione S-transferase class μ in French alcoholic cirrhotic patients

SummaryThe lack of glutathione S-transferase μ (GSTμ) was examined in 45 healthy French Caucasians and 45 alcoholic cirrhotic French Caucasians: microsamples of blood were taken and DNA amplified by the polymerase chain reaction. We have concluded that there is no relationship between this genotype and the development of alcoholic cirrhosis in these heavy consumers of ethanol.

Role of Alcohol Dehydrogenase Polymorphism in Ethanol Metabolism and Alcohol-Related Diseases

In alcohol toxicity, a lot of data point to genetic factors associated with environmental factors. These genetic factors can intervene at different levels : genetic variability in the distribution of polymorphic alcohol and aldehyde dehydrogenase isozymes (Bosron, et al., 1988) could play a role in determining individual difference in ethanol metabolism and toxicity. In the future, other polymorphisms in alcohol metabolism may be described. Polymorphism is also to be considered in detoxication and/or target organ metabolism (as collagen polymorphism in alcoholic cirrhosis)(Weiner, et al., 1988).

Identification of a new apolipoprotein E variant (E2 Arg142 → Leu) in type III hyperlipidemia

A new rare apolipoprotein E mutant was identified as we were investigating the apolipoprotein E genotype of patients with type III hyperlipidemia (HLP III). The unusual DNA restriction fragment length polymorphism profile and then the sequence analysis of a PCR amplified fragment of the probands apo E gene revealed a simple base substitution (G-->T) at nucleotide 3836. This mutation leads to the replacement of arginine by leucine at position 142 of the mature protein. The proband carried the mutant allele at the heterozygous status with an epsilon 3 allele. Subsequently, analysis of the probands fathers apo E gene showed that same mutated allele associated with an epsilon 2 allele. The two subjects presented a dysbetalipoproteinemia in which this new apo E variant could be implicated.

Primary sequence of the β-chain of badger haemoglobin

Abstract Badger (Meles meles) haemoglobin was purified by paper electrophoresis and converted into globin. Chain separation was carried out on a CM-cellulose column in the presence of 8 M urea. The β-chain was aminoethylated, purified by gel filtration and submitted to tryptic digestion. A fingerprint obtained with the enzymic digests showed 17 distinct ninhydrin-positive spots from which 20 pure peptides were isolated by further electrochromatographic separations. These peptides were sequenced using Dansyl-Edman and Ptc-Edman degradation techniques. The presence of amide residues was confirmed after aminopeptidase M hydrolysis. Taking human haemoglobin β-chain as a model, the covalent structure could be completely resolved without the help of any further overlapping technique. The following substitutions were noted (badger/human, position): Ala/Pro5, Ser/Ala13, Tyr/Phe41, Asp/Glu43, Ser/Ala70, Glu/Asp73, Lys/Ala76, Asn/His77, Lys/Thr87, Lys/Arg104 and Gln/Pro125. A comparison with other haemoglobin β-chains already sequenced shows a greater similarity with dog haemoglobin, the only example of β-chain of known structure in the order of Carnivores.

Genotyping of a patient homozygous for a rare apolipoprotein E1 [Gly127-->Asp; Arg158-->Cys] (Weisgraber allele).

SummaryWe examined the apolipoprotein E polymorphism of an obese patient presenting non-insulin-dependent diabetes, hypertension and moderate lipid disturbances. The apolipoprotein E genotyping carried out from leukocyte DNA using PCR amplification and restriction enzyme digestion demonstrated homozygosity for the rare apoE1[Gly127→Asp; Arg158→Cys] (Weisgraber allele). The nucleotide change results in a glycine to aspartic acid substitution at amino acid 127 in the apolipoprotein E2.

The β-chain of badger haemoglbin: Amino acid composition of the tryptic peptides and the N-terminal sequence to position 42

We report here the partial structure of the P-chain of the haemoglobin of the Badger (Meles meles), an animal of the hitherto poorly studied group of carnivores. The tryptic hydrolysate was resolved by electrochromatography and the amino acid composition of 15 peptides is given. The amino acid sequence to position 40 has been determined by analysis of four tryptic peptides, which are compared to the homologous peptides isolated from human P-chain. The sequence is confirmed and extended to position 42 by stepwise degradation of the whole P-chain, using a sequencer.

Action of the phosphonic analogue of tyrosine and of other tyrosine derivatives on rat liver tyrosine aminotransferase

SummaryTyrosine transamination has been investigatedin vitro with a preparation of rat liver tyrosine aminotransferase in the presence of several structural derivatives of the substrate, including the phosphonic analogue. The transamination by tyrosine aminotransferase (TAT) needs the presence in the substrate molecule of free amino and carboxylic groups, a three-carbon aliphatic chain, a para-phenolic hydroxylic function and al-configuration. Some tyrosine analogues can markedly disturb the Tyr-TAT association: the chief structural modifications are (i) the removal of the free amine function in a compound still possessing a para-hydroxylic and a carboxylic group, (ii) the change of the carboxylic function by another acidic group, especially a phosphonic one, (iii) a disubstitution in positions 3 and 5. In every situation, the presence of a parahydroxylic group is compulsory to observe an inhibitory effect.

Fingerprints of tryptic peptides of Carnivora myoglobins

Abstract The moderate evolution rate of apomyoglobins may be the support of a simplified strategy for determining unknown covalent structures within the order of Carnivora, taking the badger apomyoglobin as a model. The CNBr cleavage was followed by the isolation of three polypeptide fragments which were subsequently submitted to trypsin digestion. The fingerprints of the three hydrolysates as may be obtained from seven Carnivora species, show a fairly constant number of spots, often corresponding to identical or closely related peptides, espcially in the case of the N-terminal and C-terminal fragments.

Post-Heparin Lipolytic Activities in Chronic Renal Failure Patients in Relation to Plasma Triglycerides

Chronic renal failure (CRF) is responsible for several abnormalities of lipoprotein metabolism and represents an increased risk of atherosclerosis [1,2]. Hypertriglyceridemia is very often observed in patients suffering from terminal CRF, treated by hemodialysis or not, while plasma cholesterol is either normal or slightly elevated. Among the numerous risk factors presented by uremic patients, it is not easy to know precisely the role of hypertriglyceridemia. The general increase in all the triglyceride-rich lipoproteins is a consequence of their impaired metabolism.