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H D Hoberman

Publications and source records attributed to H D Hoberman.

At least 19 recordsLinked to original sources
PubMed1988

Reaction of tobacco smoke aldehydes with human hemoglobin.

Formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, and acrolein, all of which are constituents of tobacco smoke, were reacted in 5 mM concentration with the purified major fraction of normal adult human hemoglobin (hemoglobin Ao) in 1 mM concentration. A cigarette smoke condensate, diluted to contain 5 mM total aldehydes, was also reacted with 1 mM hemoglobin Ao. Cationic exchange high-performance liquid chromatography (HPLC) showed that the products formed from simple aliphatic aldehydes, with the exception of formaldehyde, were analogues of those formed from acetaldehyde, earlier shown by us to be imidazolidinone derivatives, that is, cyclic addition products of the N-terminal aminoamide function of alpha and beta chains. Formaldehyde and acrolein produced a heterogeneous mixture of derivatives including cross-linked hemoglobin dimers. The greater proportion of modified hemoglobins produced by condensate aldehydes resembled those formed from acetaldehyde, the most abundant aldehyde in the condensate. A smaller fraction consisted of cross-linked hemoglobin dimers, presumably due to the action of formaldehyde. Mass spectrometric and HPLC analyses of the 2,4-dinitrophenylhydrazones precipitated from the condensate documented the presence of formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, furfural, and methylfurfural. The toxicity of aldehydes is briefly discussed in the context of the findings of this study.

Aldehydes↗
PubMed1986

Reaction of acetaldehyde with hemoglobin.

Acetaldehyde reacted with hemoglobin at neutral pH and 37 degrees C to form adducts that were stable to dialysis and that were not reduced by sodium borohydride. Hemoglobin tetramers having 2, 3, and probably 4 molar eq of bound aldehyde were isolated by cation exchange chromatography. The sites of attachment of the aldehyde were the free amino groups of the N-terminal valine residues of the alpha and beta chains of hemoglobin. Derivatization of the beta chains caused a greater increase in the acidity of the hemoglobin than did derivatization of the alpha chains. Derivatization of the beta chains was also preferred over that of the alpha chains. Acetaldehyde derivatives of the N-terminal octapeptide of hemoglobin S (beta sT-1 peptide), Val-Gly-Gly, and tetraglycine were formed readily, contained 1 M eq of acetaldehyde/mol of peptide, and were not reduced by sodium borohydride. In contrast, Ala-Pro-Gly failed to form a 1:1 adduct with acetaldehyde. 13C NMR analysis of the peptide adducts formed with [1,2-13C]acetaldehyde indicated that tetrahedral diastereomeric derivatives were produced. The 13C chemical shifts of the adducts formed between hemoglobin and [1,2-13C]acetaldehyde were identical to those of the peptide adducts although resonances from the individual diastereomeric adducts at each hemoglobin site could not be resolved. The results cited above as well as other evidence indicate that acetaldehyde reacts with the amino termini of hemoglobin to form stable cyclic imidazolidinone derivatives. An exchange of acetaldehyde residues between peptides was also documented.

Acetaldehyde↗
PubMed1983

Post-translational modification of hemoglobin in alcoholism.

Hemolysates from a majority of alcoholic individuals contain a hemoglobin fraction having chromatographic properties resembling those of hemoglobin AIc, a normally occurring glycosylated hemoglobin, but differing from the latter in not being bound by boronated agarose. A hemoglobin fraction having similar properties was also isolated from human erythrocytes exposed to acetaldehyde. These observations and other evidence suggest that the abnormal hemoglobin fraction present in men and women addicted to alcohol is produced by addition to hemoglobin Ao of an aldehyde or ketone formed metabolically from ethanol and thus may serve as a diagnostic indicator of alcoholism.

Alcoholism↗
PubMed1982

Elevation of the hemoglobin A1 fraction in alcoholism.

The proportion of hemoglobin A1 was measured in 43 normoglycemic men and women admitted consecutively to an alcohol treatment center and in 41 healthy volunteers. On the average, the size of the fraction was significantly greater in the alcoholic patients than in the healthy subjects. The results of hemoglobin A1c determinations added independent evidence that this difference was not due to formation of any of the known glycosylated hemoglobins despite the fact that the alcohol-related hemoglobin was found to cochromatograph with hemoglobin A1c. The size of the hemoglobin A1 fraction was unrelated to the presence or absence of alcoholic hepatitis, although most patients having abnormally high serum hepatic enzyme activities were also found to have abnormal elevations of the A1 fraction. However, some patients with normal serum enzyme activities were among those having the highest values of the A1 fraction, indicating that the latter was a more sensitive indicator of excessive alcohol intake than were hepatic enzyme activities. The proportion of hemoglobin A1 in a patient followed over a period of 9 months rose to a maximum as the patient continued to drink. In a patient who abstained from drinking while under hospital care, the A1 fraction decreased towards normal with a half-time of 11 days. These observations are interpreted as evidence that alcohol-related hemoglobin is a product of a readily reversible reaction occurring at a maximal rate of 0.038 mM day-1, about 4 times as rapid as is the formation of hemoglobin A1c.

Adult↗
PubMed1980

A possible hemoglobin marker of alcoholism.

Human erythrocytes were found to synthesize 5-deoxy-D-xylulose-1-phosphate from added acetaldehyde and endogenous dihydroxyacetone phosphate. In separate experiments 5-deoxy-D-xylulose-1-phosphate was observed to react with hemoglobin Ao, forming a stable adduct. Formation and accumulation of this unique form of hemoglobin in the blood of alcohol users, by integrating the blood acetaldehyde concentration, would provide a dose-time record of alcohol consumption.

Acetaldehyde↗
PubMed1976

Phenformin-associated metabolic acidosis.

We report 18 consecutive phenformin-treated diabetic patients admitted to this Medical Service acutely ill with metabolic acidosis. Lactic acidosis was anticipated, and documented, in all. Also, however, though most of the patients had only weakly positive, or even negative, serum reactions with the nitroprusside reagent, all were found to have coexisting ketoacidosis, plasma 3-hydroxybutyrate averaging 7.1 mmol/L. +/- 3.9 (S.D.). This finding suggest that treatment of these patients should include insulin, and often also glucose, because most do not have marked hyperglycemia and some have hypoglycemia. The lactic acidosis in the nine patients who survivied was, on average, less severe than in the nine who died, but the difference was not statistically significant. Surivival correlated closely with the absence of shock on arrival. Only eight patients had a identifiable acute illness other than the metabolic acidosis. The other 10 patients had no discernible cause for the acute illness apart from their treatment with phenoformin. This finding raises serious doubts about whether phenformin should be used to treat patients with diabetes.

Acidosis↗
PubMed1976

Lactic acidosis in diabetic patients.

Plasma lactate and beta-hydroxybutyrate concentrations were measured during episodes of ketoacidosis and lactic acidosis in diabetics. In 39 patients with ketoacidosis, with a mean plasma beta-hydroxybutyrate concentration of 12.4 millimols/liter, the plasma lactate concentration was less than 3.6 millimols/liter in 28 and moderately elevated in 11. In seven of the latter, coexisting lactic acidosis had been suspected clinically. In these 39 patients, there was no correlation between plasma lactate and beta-hydroxybutyrate concentrations. In six of ten episodes of presumed and later proved lactic acidosis, despite negative or weakly positive serum reactions with sodium nitroprusside, the plasma beta-hydroxybutyrate concentration was elevated. Although positive, the serum reaction with nitroprusside was also misleadingly weak in five of 39 patients with ketoacidosis, including three with plasma lactate concentrations less than 3 millimols/liter.

Adult↗
PubMed1975

Alcoholic detosis.

Twenty-four chronic alcohol abusers hospitalized during a twenty-seven-month period were suspected of having "alcoholic ketoacidosis" because they had ketonuria or ketonemia with little or no glucosuria. Twenty-one had moderate or severe ketosis, with plasma 3-hydroxybutyrate of 5.2 to 22.5 mmol/L. Fifteen of this group were not diabetic, while six were later found to have mild postprandial hyperglycemia without glycosuria. Three patients who had continued to drink until shortly before admission, though at first suspected of having alcoholic ketosis, were found to have predominant lactic acidosis, with minor elevations of plasma 3-hydroxybutyrate. In contrast to previously reported patients with "alcoholic ketoacidosis", severe acidemia was uncommon in this series. Indeed, seven patients were alkalemic, because of coexisting respiratory or metabolic alkalosis. Most patients had eaten poorly for several days (and usually longer) and had allegedly decreased their alcohol intake during that period. That history, and the usual rapid clearing of ketosis simply by treatment with solutions of glucose and NaCl, suggested that acute starvation was an important factor in the pathogenesis of this disorder. Four patients were treated with insulin and four with NaHCO3 solutions. In retrospect, the need for either of these treatments was not clear. Two of the twenty-four patients died, one from circulatory failure secondary to hemorrhage and the other from pulmonary edema, but no patient died because of ketoacidosis per se.

Acidosis↗
PubMed1975

Is there a role for mitochondrial genes in carcinogenesis?

Although defective respriration is not characteristic of all tumors, recent comparative studies on the ultrastructure of normal and tumor cell mitochondria indicate that in malignant cells mitochondria deviate from normal not only in relative abundance but also in the size, form, density, and frequency of appearance of lesions. Normal and abnormal mitochondria may populate the same cell, suggesting that there may be a gradation in respiratory deficiency depending on the proportion of normal to abnormal forms. Recent advances in mitochondrial genetics suggest that aberrant mitochondria may be formed as a result of the presence of an abnormal mitochondrial genome. In analogy with the petite mutant of certain strains of yeast, animal cells may be transformed by treatment with dyes that alter the structure of their mitochondrial DNA, so that their mitochondria also become deficient in enzymes of the respiratory chain. Whether nutritional or other deficiencies are mutagenic with respect to mitochondrial DNA of animal cells is not known; nor is it known whether mitochondrial mutagenesis is causally involved in carcinogenesis. New knowledge of cytoplasmic genetics and of mitochondrial DNA and membrane structure and dynamics should encourage investigations aimed at examining the possible role of mitochondrial genes in neoplastic transformation.

Animals↗