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Biomedical subjects

D Dhermy

Publications and source records attributed to D Dhermy.

At least 91 records · Page 5Linked to original sources
PubMed1984

A variant of erythrocyte membrane skeletal protein band 4.1 associated with hereditary elliptocytosis.

A family comprising three patients (a mother and two children) with mild hereditary elliptocytosis was studied. Each patient had prominent elliptocytosis, reduced red cell deformability, and normal erythrocyte thermal sensitivity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the erythrocyte membranes in each patient showed decreased levels of band 4.1 (approximately half of the normal value) and the presence of an additional band migrating below protein band 4.2. This additional band was shown to derive from protein 4.1. Comparative partial proteolytic mapping of protein 4.1 and the additional band revealed a number of common peptides. Enzyme-linked immunoelectrotransfer blots of the patients' erythrocyte membranes using a monoclonal antibody to protein 4.1 revealed that, in addition to protein 4.1, two other bands below protein 4.2 were stained; one of these bands migrated in the same position as the additional band detected in the Coomassie Blue-stained gels. Immunoblotting of the patients' whole cells using the antibody to protein 4.1 revealed that this altered band 4.1 occurred as such in the intact red cell. SDS-PAGE of protein 4.1 purified from one patient showed the presence of two lower molecular weight bands below protein 4.1; the lower band migrated in the same position as the additional band found on SDS-PAGE of the patients' erythrocyte membranes. The patient's purified protein 4.1 displayed a decrease of about 40% in the binding activity with crude spectrin extracted from normal controls. Spectrin-spectrin interactions were normal in the three patients. The additional band present in the patients' red cell membranes probably represents a proteolytic degradation product. This alteration, present both in whole cells and isolated membranes, might affect the intact cells in vivo. We suggest that the patients' erythrocyte membrane instability may be related to the presence of an abnormal protein 4.1 whose modulatory influence on the spectrin-actin interaction in the skeleton is defective.

Adult↗
PubMed1984

Superoxide dismutase, catalase, and glutathione peroxidase in red blood cells from patients with malignant diseases.

Superoxide dismutase (SOD), catalase, and glutathione peroxidase activities have been determined in red blood cells isolated from patients with acute myelogenous leukemia, chronic lymphocytic leukemia, Hodgkin's disease, lymphosarcoma, and various visceral cancers. In all investigated cases, both catalase and glutathione peroxidase were found to be in normal ranges of activity. In the group of patients with visceral cancers, SOD activity was found to be normal as well. In contrast, SOD activity was found to be significantly increased in red blood cells from patients with acute myelogenous leukemia and lymphoproliferative syndromes. This increase in superoxide level was not related to either reticulocytosis or hypochromic anemia. No relationship was found between the SOD level and the stage, the extension of the disease, or the presence of an inflammatory syndrome. The highest SOD levels were observed in untreated patients or during the early time period of the treatment. SOD levels further decrease as a function of the increase in the duration of the treatment. These results suggest an abnormality in the regulation of the expression of the SOD gene in the pluripotent stem cells.

Catalase↗
PubMed1984

[Primary lymphomas of the digestive tract. Therapeutic results of a series of 35 cases].

We report the results of a diagnosis and treatment scheme used in 35 patients with primary gastrointestinal lymphoma studied between 1972 and 1982. There were 17 lymphomas of the stomach, 13 of the small bowel, 6 of the colon and/or the rectum. According to the Kiel classification and/or the International Working Formulation, 10 were "good risk" lymphomas, 25 were "bad risk" lymphomas. According to the Musshoff modified Ann Arbor staging classification, 16 were localized lymphomas (stage IE and II1E), 19 were disseminated lymphomas (stages II2E, IIIE or IV). The treatment scheme included laparotomy for staging and resection, total abdominal irradiation (until 1977), and polychemotherapy with or without adriamycin depending on histologic grade. The median survival was greater than the median follow-up with a survival plateau at 0.53 after 47 months. Amongst the prognostic factors studied, the digestive initial localization had no prognostic significance; on the other hand, survival depended on abdominal extension, histologic grade according to the classifications used for lymph-nodes lymphomas, and resection possibilities, and especially on achievement of complete remission. These good results emphasize the importance of combining surgical resection with chemotherapy and early assessment of the treatment in order to rapidly obtain complete remission, the way of achieving prolonged survival.

Adult↗
PubMed1983

[Neonatal hemolysis secondary to congenital poikilocytosis].

Hereditary pyropoikilocytosis is a congenital haemolytic anaemia recently described. A new case is reported in which the condition was diagnosed by a study of erythrocyte membrane proteins in the parents. The unusual clinical features of this case lead to a discussion of the relationship between hereditary pyropoikilocytosis and other rare forms of elliptocytosis in children.

Anemia, Hemolytic, Congenital↗
PubMed1983

Immune disorders in agnogenic myeloid metaplasia: relations to myelofibrosis.

Tests for a dysimmune state were done in an unselected group of 67 patients with agnogenic myeloid metaplasia (AMM). The results were compared to those of 56 patients with polycythaemia vera (PV). 75% of AMM patients versus 32% of PV patients had various abnormalities. The most frequent disorders among AMM patients were serum antinuclear and anti smooth muscle autoantibodies (10.3% each), a positive test for rheumatoid factor (21.7%), a polyclonal increase in serum immunoglobulin levels (46.8%) or a serum monoclonal component (9.7%), a positive direct Coombs' test (19%), an anti I autoantibody (30%). In AMM patients there was no relationship between age, sex, importance of splenic enlargement, time from diagnosis or treatment and the present of a dysimmunity. Furthermore, in AMM patients, but also in PV patients, it seems that the more frequent and numerous these abnormalities the more severe is the myelofibrosis. Like other previous studies, these results suggest a lymphoid cell involvement in AMM and a role for these immune disorders in the pathogenesis of myelofibrosis.

Adult↗
PubMed1983

A phenomenological difference between membrane skeletal protein complexes isolated from normal and hereditary spherocytosis erythrocytes.

Membrane skeletons may be obtained from human erythrocytes by extraction with non-ionic detergent. When treated under defined conditions with a cAMP-independent kinase preparation from normal membranes, a suspension of these membrane skeletons sets to a gelatinous mass. Membrane skeletons from the cells of hereditary spherocytosis patients fail to show this response. Those from subjects with some other haemolytic anaemias do not share the abnormality. The gelation process could be shown also to occur with normal membrane skeletons, extracted at high ionic strength, and containing essentially only the structural protein constituents, spectrin, actin, 4.1 and 4.9. It also occurred rapidly when a column-purified kinase preparation was used, so that no significant amounts of contaminating proteins were introduced. Added spectrin, 4.1 or actin in moderate amounts did not induce gelation in the presence of ATP. Cytochalasin E did not perturb the gelation process. Gelation required ATP as well as kinase, and did not occur when the non-hydrolysable analogue, AMP X PNP, was used instead. Gelation was accompanied by phosphorylation of the spectrin alone, and is thus evidently a consequence of the modification of its properties by this means. Inhibition of phosphorylation by added adenosine retarded gelation. It may be inferred that phosphorylation of spectrin generates new, probably weak, non-covalent interactions between cytoskeletal constituents that cause association of the isolated cytoskeletons. A semi-quantitative method of observing the gelation process, based on the time of incubation before the membrane skeleton suspension ceases to flow under gravity at a low shear, is described.

Actins↗
PubMed1983

[Congenital hemolytic anemia with erythrocyte thermal instability and defect of spectrin tetrameric polymerization. Study of erythrocyte deformability in a new case of hereditary pyropoikilocytosis using diffraction viscosimetry].

Hereditary pyropoikilocytosis (HPP) is a rare congenital hemolytic anaemia observed so far in patients of black extraction. In many cases, the severity of the anaemia has led to early splenectomy, which uniformly improved the hematological conditions. The disease is characterized by extreme anisocytosis and poikilocytosis with erythrocyte fragmentation. The pathognomonic feature is the abnormal thermal sensitivity of red cells which fragment in vitro at 45-46 degrees C (instead of 49 degrees C in normal subjects). In the case reported here, erythrocyte fragmentation (which appears at 43 degrees C) and increased osmotic fragility are studied using the Ektacytometer. Observation of different erythrocyte fractions isolated by differential centrifugation shows the extreme heterogeneity of the erythrocyte population. Studies of erythrocyte membrane proteins confirm that the disease is related to defective dimer-dimer association of spectrin which is the major membrane skeletal protein. This molecular spectrin abnormality in accounting for the membrane instability is recognized to a lesser degree in the asymptomatic mother. This may be of use in the diagnosis of HPP which is difficult to establish in a transfusion-dependent infant.

Anemia, Hemolytic, Congenital↗
PubMed1982

[Contribution of immunochemical methods to the study of human red-cell membrane proteins].

Together with the classical technics of biochemical analysis, immunological methods have led to differentiate, characterize the main red-cell membrane proteins and to better understand their organization. Immunological methods were particularly involved in the study of: 1) the membrane skeletal proteins, specially spectrin which localization in the membrane, structure and functions have been specified; 2) the principal integral proteins, glycophorin and protein band 3, the transmembrane orientation of which has been corroborated by topographic immunological mapping of their cytoplasmic domain; 3) the anchor chain protein, linking the membrane skeleton to the transmembrane proteins. These methods could further help to a better understanding of the membrane structure. Two kinds of work can be considered using monoclonal antibodies provided by the hybridoma method: 1) the purification by immunoabdsorbent technics, of quantitatively minor membrane proteins, would allow to study their structure and functions; 2) an immunological mapping with monoclonal antibodies specific against each of the skeleton proteins, of membrane preparations observed in electronic microscopy, would permit to visualize the real architecture of these different proteins in the red-cell membrane.

Actins↗
PubMed1982

[Human red cell cytoskeleton: structure, functions, abnormalities (author's transl)].

Associated with the red cell membrane cytoplasmic surface, the cytoskeleton is composed of a protein complex. This structure is a major element of membrane stability, shape and flexibility. Among the constitutive proteins, spectrin, red-cell actin and protein band 4.1 are quantitatively and structurally the most important. Some elements, relative to structure, stoichiometry and interactions between these proteins begin to be understood, specially owing to in vitro studies of reassembling cytoskeleton structures from purified constitutive elements. Besides, the nature of some interactions between the cytoskeleton and the red cell membrane has been specified. Nevertheless, it is not possible at the present time to establish an architectural picture of the cytoskeleton anatomy, and the factors actually regulating this structure physiology are not characterized. Understanding of the normal cytoskeleton will perhaps be helped by studies of abnormal models which cytoskeleton protein structure and function could be defective but this has not so far been formally demonstrated.

Actins↗
PubMed1982

Spectrin beta-chain variant associated with hereditary elliptocytosis.

An electrophoretically fast-moving variant of the spectrin beta-chain was discovered in the erythrocyte membranes of a woman and her father who both exhibited elliptocytosis and mild hemolytic anemia. This abnormal beta'-subunit (Mr = 214,000) co-existed with a decreased normal beta-chain and represented about half of the total beta-chains in the membrane. In contrast to the spectrin beta-chain, the beta'-chain was phosphorylated neither in the membrane by endogenous protein kinases nor in solution by pure membrane casein kinase whether or not the spectrin was dephosphorylated by erythrocyte cytosolic spectrin phosphatase. The presence of the beta'-chain was associated with a defective self-association of spectrin dimer to form tetramer as manifested by: (a) an excess of spectrin dimer in the 4 degrees C spectrin crude extract, (b) a defective self-association of the spectrin dimer in the 37 degrees C crude spectrin extracts. Gel electrophoretic analysis of the tetramer and dimer species isolated from the proband's 4 degrees C extract showed that the tetramer contained trace amounts of the beta'-chain, whereas in contrast, a large proportion of beta'-chain was present in the dimer. These results demonstrated the responsibility of the beta'-chain for the defective reassociation of spectrin dimer into tetramer. The study of this abnormal spectrin confirms the participation of spectrin beta-chain in dimer-dimer association and strongly suggests that the phosphorylation sites of the normal beta-chain are located at the end of the molecule involved in the dimer-dimer interactions.

Adult↗
PubMed1982

[Contribution of immunochemical methods to the study of human red-cell membrane proteins (author's transl)].

Together with the classical technics of biochemical analysis, immunological methods have led to differentiate, characterize the main red-cell membrane. proteins and to better understand their organization. Immunological methods were particularly involved in the study of: 1) the membrane skeletal proteins, specially spectrin which localization in the membrane, structure and functions have been specified; 2) the principal integral proteins, glycophorin and protein band 3, the transmembrane orientation of which has been corroborated by topographic immunological mapping of their cytoplasmic domain; 3) the anchor chain protein, linking membrane skeleton to the transmembrane proteins. These methods could further help to a better understanding of the membrane structure. Two kinds of work can be considered using monoclonal antibodies provided by the hybridoma method : 1) the purification by immunoadsorbent technics, of quantitatively minor membrane proteins, would allow to study their structure and functions ; 2) an immunological mapping with monoclonal antibodies specific against each of the skeleton proteins, of membrane preparations observed in electronic microscopy, would permit to visualize the real architecture of these different proteins in the red-cell membrane

Ankyrins↗
PubMed1981

In vitro phosphorylation of the red blood cell cytoskeleton complex by cyclic AMP-dependent protein kinase from erythrocyte membrane.

Hydrosoluble proteins extracted from human erythrocyte ghosts by dialysis at low ionic strength and alkaline pH contain a cyclic AMP-dependent protein kinase which phosphorylates in vitro the cytoskeleton components in crude extracts. Spectrin components 1 and 2, actin and protein band 4.1 undergo this cyclic AMP-dependent endogenous phosphorylation together with low molecular weight peptides solubilized with the cytoskeleton in hydrosoluble extract. However, pure spectrin and purified erythrocyte G-actin were not phosphorylated by purified cyclic AMP-dependent protein kinase from erythrocyte membrane. Purified G-actin when added free to crude extract does not undergo phosphorylation by the cyclic AMP-dependent protein kinase present in this extract. In contrast, purified cyclic AMP-dependent protein kinase added either to crude extract or to the purified cytoskeleton complex (spectrin, actin and protein band 4.1), phosphorylates spectrin, actin and protein band 4.1. We can conclude that (1) cyclic AMP-dependent phosphorylation of red cell cytoskeleton occurs in vitro only when the cytoskeleton components are in a complexed form; (2) red cell actin, like other cellular actins, may be phosphorylated by cyclic AMP-dependent protein kinase but only in the oligomeric form and not in the G form.

Actins↗
PubMed1981

Anti-spectrin in sera containing smooth muscle autoantibodies from patients with chronic active hepatitis.

Sera from patients with chronic active hepatitis containing anti-smooth muscle autoantibodies (SMA) react against rabbit muscle actin as well as human red cell spectrin. These anti-spectrin antibodies recognize the same antigen as rabbit anti-human spectrin antibodies and are not involved in the staining pattern given by SMA-containing sera tested with smooth muscle sections. These anti-spectrin antibodies probably recognize an antigenic structure common to both spectrin and another as yet undetermined molecule (which however is not likely to be myosin).

Actins↗
PubMed1981

[Human red cell cytoskeleton: structure, functions, abnormalities (author's transl)].

Associated with the red cell membrane cytoplasmic surface, the cytoskeleton is composed of a protein complex. This structure is a major element of membrane stability, shape and flexibility. Among the constitutive proteins, spectrin, red-cell actin and protein band 4.1 are quantitatively and structurally the most important. Some elements, relative to structure, stoichiometry and interactions between these proteins begin to be understood, specially owing to in vitro studies of reassembling cytoskeleton structures from purified constitutive elements. Besides, the nature of some interactions between the cytoskeleton and the red cell membrane has been specified. Nevertheless, it is not possible at the present time to establish an architectural picture of the cytoskeleton anatomy, and the factors actually regulating this structure physiology are not characterized. Understanding of the normal cytoskeleton will perhaps to helped by studies of abnormal models which cytoskeleton protein structure and function could be defective but this has not so far been formally demonstrated.

Actins↗
PubMed1980

[Acute agranulocytosis. Clinical study of thirty-two cases (author's transl)].

Acute agranulocytosis is a serious accident if the nature of the accident and the responsible drug are ignored or if it happens to a weak patient. Among thirty two cases of hospitalization, probably chosen according to their seriousness, the authors recall the diversity of the symptoms, the risk of the abuse of the "pyrazol compound" (70% of agranulocytosis) and the frequency of relapse (30%). The prognosis depends on the risk of infection. Septicemy is rare (15%), often foreseeable depending on the state of the patient. Agranulocytosis remains serious in spite of a wide range antibiotics administered in the early stages.

Acute Disease↗