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Biomedical subjects

A Kahn

Publications and source records attributed to A Kahn.

At least 631 records · Page 35Linked to original sources
PubMed1976

Chronic haemolytic anaemia in two patients heterozygous for erythrocyte pyruvate kinase deficiency. Electrofocusing and immunological studies of erythrocyte and liver pyruvate kinase.

Two patients with mild chronic haemolytic anaemia, a mother and her son, were found to be heterozygous for erythrocyte pyruvate kinase deficiency. In the red blood cells the enzymatic activity was reduced by about 50% and the residual PK had normal kinetic properties, stability and electrofocusing pattern. The PK antigen concentration was also decreased by half, so that the ratio of the enzymatic activity to the immunological reactivity (i.e. the molecular specific activity) was normal. In the son's liver PK enzymatic activity was slightly reduced and, above all, an abnormal active form, more anodic than normal PK, was detected by electrofocusing. The propositus's liver PK was also slightly thermo-unstable. It is suggested that the patients were heterozygous for an unstable PK variant which is found in liver, nucleated tissue actively synthesizing proteins, but which disappeared from the erythrocytes because of its unstability.

Adult↗
PubMed1976

Aging and accuracy of protein synthesis in man: search for inactive enzymatic cross-reacting material in granulocytes of aged people.

Enzyme activities and immunological reactivities of seven different enzymes have been assayed in the polymorphonuclear leukocytes from 10 newborns, 10 aged (over 80 years old) and 10 young adults (20-30 years old). Polymorphonuclears have been chosen because both in the newborns, and in the aged people, they are young cells whose life span is a few hours only. Five cytoplasmic enzymes have been immunologically studied by means of monospecific antienzyme sera: leukocyte pyruvate kinase by immunoinactivation, glucose-6-phosphate dehydrogenase and glucose phosphate-isomerase by electroimmunodiffusion, lactic dehydrogenase (muscle-type) by radial immunodiffusion. Two lysosomal enzymes (alpha-mannosidase and beta-glycuronidase) have been titrated immunologically with the same polyvalent antihuman leukocyte rabbit serum. Small but significant differences in activity were observed for several of the enzymes. By contrast, no significant difference was found, for any of the seven enzymes, as regards the ratio enzyme activity/immunological reactivity, between newborns, young adults and aged people. These results of not support the theory that a decreased accuracy of the protein synthesis machinery is responsible for aging and death. By contrast, the authors emphasize that the enzyme abnormalities reported by various authors in old animals or in old fibroblast cultures closely resemble those demonstrated to be "post-translational modifications" in the case of human glucose-6-phosphate dehydrogenase.

Adult↗
PubMed1976

Human platelet glucose-6-phosphate dehydrogenase. Total purification, kinetic studies and relationship with enzyme from other blood cells.

Human platelet G-6-PD has been highly purified, to homogeneity, and its kinetic, electrophoretic and immunological characteristics have been studied. Platelet G-6-PD differs from erythrocyte or leukocyte enzymes by an increased Michaelis constant for G-6-P and a slow activity at the acid pHs. By electrofocusing only a main active band (band a) of platelet G-6-PD was found. The incubation at 37 degrees C in the presence of NADP+ and dithiothreitol normalize Km-G-6-P of platelet G-6-PD; the incubation with boiled and ultrafiltered leukemic granulocyte extracts led to an anodisation of G-6-PD active forms, a decrease of the molecular specific activity and a further increase of Km-G-6-P; these last modifications are the same as those undergone by G-6-PD incubated in crude extracts of normal or leukemic granulocytes.

Blood Platelets↗
PubMed1976

Human granulocyte phosphoglycerate kinase. Purification by double affinity elution and immunological study.

Human phosphoglycerate kinase has been totally purified from leukemic granulocytes by double 'affinity elution' with ATP and 3-phosphoglycerate. This purification procedure allowed to obtain 19 mg of protein, specific activity of which was 400 IU/mg i.e. a 105-fold purification and an overall yield of 47%. Purified enzyme was homogenous when tested by acrylamide sodium dodecyl sulfate electrophoresis and immunodiffusion. Specific antibodies raised in rabbits totally inactivated phosphoglycerate kinase of crude extracts as well as of the purified preparation. The molecular specific activity (i.e. the ratio enzyme activity/immunological reactivity) was identical in leukocytes, platelets, erythrocytes and was identical in these cells to the value found for the totally purified phosphoglycerate kinase.

Antigen-Antibody Reactions↗
PubMed1976

[Mechanisms of congenital erythrocyte enzyme deficiencies associated with hemolytic anemia].

The search for a mechanism for red cell enzyme deficiency associated with congenital hemolytic anemia, requires one to determine the kinetic and thermodynamic properties of the enzyme reaction and study the physico-chemical and immunological characteristics of the protein which supports enzyme activity. The technique of iso-electric focalisation and the use of specific anti-enzyme antibodies, is the reason for recent progress in the understanding of the mechanism of these deficiencies. Examples of application of these techniques are given in relation to glucose-6-dehydrogenase, pyruvate kinase, glucose phosphate isomerase, phosphofructokinase and phosphoglycerate kinase of deficiencies showing the multiplicity of the molecular mechanisms.

Anemia, Hemolytic, Congenital↗
PubMed1976

Causal mechanisms of multiple acquired red cell enzyme defects in a patient with acquired dyserythropoiesis.

A patient with an unclassified form of acquired dyserythropoiesis was found to have multiple defects in erythrocyte enzyme activity, involving especially pyruvate kinase (PK), glucose phosphate isomerase (GPI), and phosphofructokinase (PFK). The PK activity defect was associated with a normal concentration of PK-related antigen, and the enzyme could be reactivated during the procedure of partial purification of the enzyme. The concentration of GPI-related antigen was as reduced as the GPI enzymatic activity, and the defect was not improved by any treatment (cross-incubation of red cells or treatment of the hemolysate by SH reagents); the residual enzyme had a normal stability to heat, and a normal electrophoretic and electrofocusing pattern. The PFK activity defect was not improved either by cross-incubation of red cells or by treatment with SH reagents. Immunologic data with antimuscle and antileukocyte antisera seemed to indicate that the defect involved especially the muscle-type subunit of erythrocyte PFK. In agreement with this assumption was the fact that deficient PFK was markedly more inhibited by ATP than normal enzyme. Changes similar to those of deficient PFK herein studied were noted for PFK of unfractionated erythrocytes from premature newborns or of "old" erythrocytes from full-term infants. It appeared that each of the three enzyme defects detected in the patient could be due to a different mechanism, involving post-translational changes, decreased synthesis, and possible reversion of the genetic regulation mechanisms of the abnormal erythroid precursors toward a fetal type. The possible relationships between these various phenomena and the nature of a hypothetical common underlying cause are discussed.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1976

[Correlation between permeabiltiy to albumin and levels of cyclic adenosine monophosphate in the incubated rat mesentery].

Histamine, bradykinin and prostaglandin E1 increase the permeability coefficient of albumin; this effect is mimicked by dibutyryl-cAMP and by theophylline. They also cause a significant rise in the cAMP levels of the incubated tissue. Serotonin has lesser activities on these parameters. Presumably, the first three mediators control the transcellular passage of albumin by increasing the cAMP content of the tissue, serotonin being less effective. These findings on the mesentery seem to have a couterpart in vascular tissue as shown by others using different methods.

Animals↗
PubMed1975

Gd(--) Abrami: a deficient G-6PD variant with hemizygous expression in blood cells of a woman with primary myelofibrosis.

A new deficient G-6PD variant, Gd(--) Abrami, was found in granulocytes, platelets and red blood cells of a 65-year-old woman with myelofibrosis. Enzyme and immunological titrations showed that only the deficient variant was present in blood cells whereas both the normal and abnormal enzymes were found in the fat cells of this patient. These results seem to indicate that the granulocytes, platelets and erythrocytes of this woman with myelofibrosis have arisen from a single abnormal precursor the functional X chromosome of which is the one carrying the abnormal G-6PD gene.

Adipose Tissue↗
PubMed1975

Molecular mechanism of erythrocyte pyruvate kinase deficiency.

Erythrocyte pyruvate kinase (PK) from 5 patients with cogenital non-spherocytic hemolytic and erythrocyte PK deficiency have been studied by immunological methods and electrofucusing. L type immunologically related PK was titrated in crude hemolysate with anti human liver L type PK rabbit serum and M2 type immunologically related PK with anti human leukocyte M2 type PK serum. After partial purification, molecular specific activity of erythrocyte PK was measured by immunoinactivation and electroimmunodiffusion and anti L type PK serum. Partially purified erythrocyte PK was focused on continuous sucrose gradient with 2% ampholines covering the pH range 5--8. PK enzymatic deficiency was due two times to a lowered molecular specific activity of the PK variants, the concentration of PK antigen being in the normal range. In the 3 other cases enzyme activity and immunological reactivity were likewise lowered. In the 2 patients with the most marked erythrocyte PK deficiency about 50% of the residual activity in crude hemolysate were non inhibited by anti L type PK serum, but were inhibited by anti M2 type PK serum. In 3 patients, the electrofocusing pattern of partially purified PK was significantly different from than of normal controls. In conclusion, the heterogeneity of the molecular mechanisms of the deficiency on the one hand, and the abnormalities of electrofucusing patterns on the other hand, seem to indicate that erythrocyte PK deficiency is due to the synthesis by muted structural genes of various abnormal PK molecules.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1975

Glucose phosphate isomerase deficiency with hereditary hemolytic anemia in a Spanish family: clinical and familial studies.

A new case of glucose phosphate isomerase deficiency associated with cogenital nonspherocytic hemolytic anemia is described in a 12-year-old girl of Spanish origin. The parents exhibited erythrocyte glucose phosphate isomerase activity between 50 and 60% of normal. The enzyme of the propositus had normal Michaelis-Menten constants both for F-6-P and G-6-P, but abnormal pH optimum and decreased heat stability at 48 degrees C. On starch-gel electrophoresis the father's enzyme was normal but the mother's showed a cathodic migrating band in addition to the normal one. The enzyme from the propositus exhibited only one band with cathodal mobility of 116% of the main band found in normal subjects. It is postulated that the propositus is double heterozygous for two abnormal alleles, and the mother contributes a mutant allele with abnormal electrophoretic mobility and thermolability at 48 degrees C whereas the father contributes an allele without enzymatic activity.

Alleles↗