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Biomedical subjects

H Wajcman

Publications and source records attributed to H Wajcman.

At least 145 records · Page 8Linked to original sources

Separation of pure toxic peptides from a beta-gliadin subfraction using high-performance liquid chromatography.

The beta v subfraction was isolated from peptic-tryptic digests of beta-gliadin by chromatography on Biogel P-10 and applied to a Lichrosorb RP-18 or a mu-Bondapak C-18 column. Fractionation was achieved using reverse-phase high-performance liquid chromatography with a linear gradient of acetonitrile in ammonium acetate. A better resolution was obtained with the mu-Bondapak column. The first-eluted peptides a, b and c1 appeared to be well purified and apparently uncontaminated. Analysis of peptides a and b showed that they contained 40 to 42% glutamine/glutamic acid, 20 to 23% proline, 14 to 16% valine and 8 to 10% leucine. They had valine as the N-terminal amino acid and their molecular mass was estimated as 5500 using sodium dodecylsulfate electrophoresis after dansylation. Peptide c1 differed from peptides a and b in containing less valine and leucine and additional amino acids such as threonine, phenylalanine and tyrosine. In addition, it had a lower molecular mass (approximately 5000) and serine as the N-terminal amino acid. Peptide b exhibited an obvious cytotoxicity for cultured coeliac jejunal mucosa at a very low concentration (0.01 g/l) and was the most toxic peptide.

Amino Acids↗

Hemoglobin Maputo: a new beta-chain variant (alpha 2 beta 2 47 (CD6) Asp replaced by Tyr) in combination with hemoglobin S, identified by high performance liquid chromatography (HPLC).

During a routine hematological investigation, a slowly-moving hemoglobin variant was detected in a 2-year-old child from Maputo (Mozambique) in combination with hemoglobin S. Structural studies carried out by HPLC demonstrated a previously unreported amino acid substitution, beta 47 (CD6) Asp replaced by Tyr. The new hemoglobin variant has been named hemoglobin Maputo.

Amino Acid Sequence↗

Minor hemoglobin components in diabetic and uremic patients.

Hemoglobins A1c and A1a+b were measured by an automated chromatographic method in 11 control subjects, 100 diabetics and 30 subjects with renal failure not induced by diabetes. Hb A1c was higher in diabetics than in controls (8.26 +/- 0.31 versus 5.24 +/- 0.28, p less than 0.01) and strongly correlated with blood glucose values for the preceding 4 months. In poorly controlled diabetics, submitted to an intensive therapeutic program, Hb A1c decreased rapidly. Hb A1c was slightly but significantly elevated in the uremic, non-diabetic patients who were not submitted to periodic hemodialysis: 6.42 +/- 0.32, p less than 0.05. It returned, in hemodialyzed patients, to a level not significantly different from the control value. Hb A1a+b was elevated in diabetic subjects (2.43 +/- 0.04 vs. 1.55 +/- 0.01 in controls, p less than 0.001). It was also higher in the uremic patients (2.71 +/- 0.14, p less than 0.001). No decrease occurred in the hemodialyzed patients (3.27 +/- 0.31). Glycosylated hemoglobin values, as routinely estimated and expressed under the name of "Hb A1", should be interpreted with caution in patients with renal failure. Methods discriminating Hb A1a+b have to be used.

Diabetes Mellitus↗

[Recent data in the biology of sickle cell disease (author's transl)].

A great deal of work has been in the recent years concerning sickle cell anemia, both its theoretical aspects and its medico-social consequences being involved. From the pathophysiological point of view, investigations have resulted in a better knowledge of the mechanism of the hemoglobin S polymerization. Other factors such as the role of the membrane, the ionic environment, the rheologic conditions have also been emphasized. These known disorders may explain the high clinical polymorphism of the disease. They are also the basis of a research for a potential specific treatment. Two factors have been specially investigated as potentially responsible for a benign course of the disease, namely fetal hemoglobin and an associated alpha-thalassemia. As a new field of investigation, a DNA polymorphism close to the beta-gene and linked to the mutation itself has been demonstrated. It proves the pluricentric origin of this mutation. It is also a tool for antenatal diagnosis of the homozygous forms of the disease using amniotic fluid cells. Finally the possible direct culture of P. falciparum as allowed a better understanding of the equilibrium between malaria and sickle cell anemia.

Anemia, Sickle Cell↗

[Polymorphism of hemoglobins D in Ivory Coast: Hb Korle Bu (beta 73 (E17) Asp leads to Asn), Hb Avicenna (beta 47 (CD6) Asp leads to Ala) and Hb Cocody (beta 21 (B3) Asp leads to Asn) (author's transl)].

A recent screening performed at the CHU Cocody in Abidjan (Ivory Coast) revealed six cases of hemoglobin "D". The use of a rapid strategy based on isoelectric focusing studies, finger-printing, reverse phase high performance liquid chromatography and solid phase microsequence technique led to the characterization of three abdominal hemoglobins. The first variant corresponded to the Hb Korle Bu (beta 73 (E17) Asp leads to Asn) (pI = 7.210) which is common in this country. The second, Hb Avicenna (beta 47 (CD6) Asp leads to Ala) (pI = 7.225) has not yet been reported in Africa. The last one was a new variant, Hb Cocody (beta 21 (B3) Asp leads to Asn) (pI = 7.205). A large number of hemoglobin "D" have been detected in European, American negroes, Amerindian or Asiatic populations, but only few observations were reported in Africa. Large screenings and discriminative methodologists must provide information on the polymorphism of hemoglobin D in the African population.

Chemical Phenomena↗

Minor haemoglobin fractions in uraemic and in diabetic patients.

Using a high resolution automated chromatographic method, the levels of the different minor haemoglobins Hb A1a, A1b, and A1c were measured in 20 healthy controls, in 20 patients with chronic renal failure, in 20 uraemic patients on intermittent haemodialysis, and in 20 insulin-dependent diabetic patients. In uraemic non haemodialysed patients, the levels of the three minor fractions were increased significantly. The two fractions Hb A1b and A1c were normalised subsequent to haemodialysis, whereas the level of Hb A1a was higher in the haemodialysed than in the uraemic non haemodialysed group. In both groups of uraemic patients, no correlation was found between the minor Hb fractions and the corresponding serum creatinine, uric acid, urea, phosphorus, bicarbonate and blood glucose levels. In diabetic patients, the three minor fractions were increased. As expected, Hb A1c and glucose concentrations were tightly correlated. No correlation was found between blood glucose levels and Hb A1a, whereas a correlation existed between blood glucose levels and Hb A1b. It is concluded that the increase of minor haemoglobin fractions in renal failure does not only reflect the glucose intolerance. Renal failure itself causes an increase of the three minor fractions. Overall assay of the minor haemoglobin components (Hb A1) may lead to misinterpretation in case of diabetic patients with chronic renal failure.

Adult↗

[Effect of long-term metformin treatment on the development of diabetes in genetically diabetic mice (DBM) (author's transl)].

Genetic diabetic obese, hyperinsulinaemic mice of the DBM (db/db) strain received long-term metformin. The drug was given orally (200 mg/kg twice a day) by gastric intubation starting from the 13th week of age to the 42 th. A continuing hypoglycemic effect was observed with a simultaneous decrease of HbA1c. The immunoreactive plasma insulin and body weight of treated homozygous mice were higher than those of homozygous controls. No significant modification of food consumption and blood lipids was noted. Pancreatic islets of homozygous controls showed, by light and electron microscopy, a characteristic hypersecreting appearance at 25 th week compared to that of heterozygous animals. Morphological dedifferentiation (canalicular changes and foreign cell colonization) followed in most cases at the 42 th week with reduction in B-cells. Pancreas of treated mice was similar to that of controls at 25 th but showed less B-cell exhaustion and islet degeneration at the 42 th week, explaining higher plasma IRI concentration.

Animals↗

[Glycosylation of hemoglobin and the minor hemoglobins : techniques and diagnostic study (author's transl)].

Hemoglobin Alc is the result of non-enzymatic binding of a glucose molecule at the NH2 terminal of the beta chain. Assay of glycosylated hemoglobin is of great utility for the control efficacity of antidiabetic treatments, since such levels provide the clinician with an excellent index of glucose metabolism over the weeks preceding the assay. Methods proposed for this assay include isoelectric focalization, colorimetric assays during thio-barbituric acid and especially, cation exchange chromatography. When automated, this last technique allows selective assay of Hb Alc and appears to provide the most accurate results. Certain causes of error must nevertheless be considered, in particular more rapid turnover of the erythrocytic population and the presence of Hb F which, in all chromatographic techniques, is eluted along with Hb Alc.

Chromatography, Ion Exchange↗

Hemoglobin Barcelona beta 94 (FG1) Asp leads to His : a new hemoglobin Variant with increased oxygen affinity.

A new variant, Hb Barcelona (beta 94 Asp leads to His) found in a Spanish family presenting with a mild polycythemia, is described. Its increase in oxygen affinity is explained by the rupture of the salt-bridge between beta 94 Asp and beta 146 His which normally stabilizes the deoxystructure and accounts for approximately half of the Bohr effect. A comparison between the estimated oxygen transport to the tissues by the blood from a patient with Hb Kempsey and that of the patients with Hb Barcelona showed, in the latter cases, that an almost normal oxygen delivery was obtained by the increase of the hemoglobin level.

Chemical Phenomena↗