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Biomedical subjects

A Sobel

Publications and source records attributed to A Sobel.

At least 145 records · Page 8Linked to original sources

[Treatment of severe or vasculitis associated forms of rheumatoid arthritis by plasma exchanges (author's transl)].

Five patients with typical seropositive rheumatoid arthritis were treated by plasma exchange. All patients had severe affections resistant to conventional treatment, while in four cases the disease involved extra-articular localizations: rheumatoid nodules (3 cases), polyneuritis (1 case), skin necrosis (1 case). Each patient received between 5 and 10 plasma exchanges over a period of 3 to 4 weeks. No major complications were observed. Immediate results were very good in all cases, as shown by absence of clinical expression of the arthritis, marked regression in extra-articular symptoms, and reduction in erythrocyte sedimentation rate without parallel alterations in rheumatoid factor levels. Improvement lasted for only a few weeks in 3 patients, in one case preceded by an acutely painful episode. In the remaining 2 cases, with associated vasculitis, improvement has been sustained for a period that now exceeds one year. Results are compared with those reported in the published literature, and the mode of action and indications for plasma exchange in rheumatoid arthritis discussed.

Adult↗

Nephrotic syndrome associated with T-cell lymphoma.

Glomerulopathies associated with non-Hodgkin's malignant lymphomas have been observed rarely. Previous reports have never determined the cell type of the lymphoproliferative disorder. This report documents a case of nephrotic syndrome in a patient with T-cell derived non-Hodgkin's lymphoma. The neoplastic cell was studied in terms of cell-surface markers, cytochemical staining, and ultrastructural morphology. Nephrotic syndrome occurred shortly after the apparent onset of the lymphoma. The kidney biopsy specimen was examined by light, fluorescence, and electron microscopy. Histologic findings were consistent with the diagnosis of mild focal and segmental glomerulosclerosis. Such an association, reported here for the first time, may support the hypothesis of a pathogenetic link between acquired T-cell abnormalities and glomerular diseases with minimal histologic injury.

Adolescent↗

Consequences of alkaline treatment for the ultrastructure of the acetylcholine-receptor-rich membranes from Torpedo marmorata electric organ.

After fixation with glutaraldehyde and impregnation with tannic acid, the membrane that underlies the nerve terminals in Torpedo marmorata electroplaque presents a typical asymmetric triple-layered structure with an unusual thickness; in addition, it is coated with electron-dense material on its inner, cytoplasmic face. Filamentous structures are frequently found attached to these "subsynaptic densities." The organization of the subsynaptic membrane is partly preserved after homogenization of the electric organ and purification of acetylcholine-receptor (AchR)-rich membrane fragments. In vitro treatment at pH 11 and 4 degrees C of these AchR-rich membranes releases an extrinsic protein of 43,000 mol wt and at the same time causes the complete disappearance of the cytoplasmic condensations. Freeze-etching of native membrane fragments discloses remnants of the ribbonlike organization of the AchR rosettes. This organization disappears ater alkaline treatment and is replaced by a network which is not observed after rapid freezing and, therefore, most likely results from the lateral redistribution of the AchR rosettes during condition of slow freezing. A dispersion of the AchR rosettes in the plane of the membrane also occurs after fusion of the pH 11-treated fragments with phospholipid vesicles. These results are interpreted in terms of a structural stabilization and immobilization of the AchR by the 43,000-Mr protein binding to the inner face of the subsynaptic membrane.

Animals↗

[Colchicine treatment of renal amylosis in familial paroxysmal polyserositis (author's transl)].

Mortality in familial paroxysmal polyserositis results mainly from renal amylosis, the outcome, until recently, being always fatal. Continuous colchicine administration prevents acute relapses, but certain recent observations have demonstrated that this treatment may be able to prevent the onset of amyloid disease. It could even provoke its regression, at least if administration is during the early stages before the development of renal insufficiency. The mechanism of this preventive action against amyloid disease occurrence is discussed as a function of current knowledge of amyloidogenesis.

Adolescent↗

[Plasma exchange].

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Arthritis, Rheumatoid↗

Circulating immune complexes in patients with gram negative septic shock.

In order to explain complement components abnormalities observed during septic shock, circulating immune complexes (C.I.C.) were searched for in sera from 34 patients with gram negative sepsis by two different methods: polyethylene glycol precipitation test based on physical properties of C.I.C. and C1q deviation test based on the property of radiolabelled C1q to react with C.I.C. Serum immunoglobulins (IgG, IgA, IgM) and complement components (C1q, C3, C4) levels were simultaneously determined. Seventeen patients with minimal haemodynamic abnormalities had normal or increased levels (except C4 at 62% of normal) and in eleven cases both tests for C.I.C. were simultaneously positive. Seventeen patients with severe septic shock had a decrease in IgG, IgM C1q, C3 and C4 and none had both tests for C.I.C. simultaneously positive (P less than 10(-4)). The disappearence of C.I.C. in patients with severe septic shock associated with evidence of complement activation suggests their involvement in the pathogenesis of septic shock in man.

Antigen-Antibody Complex↗

Reconstitution of a functional acetylcholine receptor. Polypeptide chains, ultrastructure, and binding sites for acetylcholine and local anesthetics.

The 'reconstitution cycle' is composed of the following sequence of operations. Highly purified receptor-rich membranes prepared from Torpedo marmorata electric organ are exposed to pH 11 to remove the 43,000-Mr protein and dispersed into solution by sodium cholate under conditions where more than 85% of the receptor protein is in its 9-S form. Elimination of the detergent by filtration on a Sephadex column (or dialysis) yields a 'reconstituted receptor' fraction, under conditions which conserve part of the endogenous lipids, or 'reconstituted vesicles' in the presence of an excess of exogenous lipids. The polypeptide composition of these fractions was analysed by sodium dodecylsulfate gel electrophoresis. Conditions are defined for quantitative measurements of the various polypeptide chains. The 40,000-Mr chain, which is labelled by the affinity reagent 4-(N-maleimido)phenyl [3H]trimethylammonium and therefore carries the acetylcholine receptor site, is the dominant polypeptide in the alkaline-treated membranes and the reconstituted acetylcholine receptor. Electron microscopy discloses that many of the alkaline-treated membranes no longer form closed vesicles and do not show the transverse asymmetry of the native membranes observed after tannic acid fixation. In the reconstituted receptor fractions, the receptor molecules reaggregate into discs and may be exposed on both faces of the discs. In the reconstituted vesicles, receptor rosettes are integrated to the lipid vesicles. With native membranes, the radioactive local anesthetic [3H]trimethisoquin binds to three classes of sites: non-specific, low-affinity and high-affinity. Carbamylcholine causes an increase in the number of high-affinity sites up to approximately 0.7 times the number of alpha-125I-bungarotoxin sites. This ratio, the three classes of binding sites, and their regulation by carbamylcholine are conserved through the reconstitution cycle.

Acetylcholine↗

Reconstitution of a functional acetylcholine receptor. Conservation of the conformational and allosteric transitions and recovery of the permeability response; role of lipids.

The 'functional' state of the acetylcholine receptor protein has been followed during reconstitution with the fluorescent agonist [1-(5-dimethylaminonaphthalene)-sulfonamidol]-n-hexanoic acid-beta-N-trimetylammonium bromide ethyl ester (Dns-C6-Cho) and rapid-mixing techniques. Under appropriate conditions, a majority of the acetylcholine receptor sites can be recovered in a low-affinity state(s) for Dns-C6-Cho, similar to that found with the native membrane-bound receptor. This state can be slowly interconverted to a high-affinity state after rapid mixing with the agonist, and the non-competitive channel blockers, like the local anesthetics, still regulate this transition in an allosteric manner. Several experimental conditions commonly used for the solubilization of the receptor and for its purification in the presence of sodium cholate result in the failure of reconstitution: the soluble receptor protein is stabilized in a low-affinity state which can no longer be interconverted to a high-affinity state in the presence of agonists or local anesthetics. On the other hand, it is demonstrated that if the concentration of lipids remains elevated in the presence of sodium cholate, a soluble (9-S) low-affinity form of the receptor protein can be obtained which shows most of the characteristic properties of the membrane-bound receptor and in particular the slow interconversion to the high-affinity state and the effect of local anesthetics on this transition; furthermore, in these conditions the soluble protein can be manipulated ad libitum and submitted, for instance, to column filtrations and sucrose gradient centrifugations in the presence of detergent, without losing its characteristic conformational and allosteric transitions. After elimination of the detergent this form yields a reconstituted receptor which presents binding properties identical to those of the native membrane-bound receptor and leads to the formation of vesicles which exhibit carbamylcholine-sensitive ion fluxes. A necessary and sufficient condition for functional reconstitution is therefore the conservation, in the presence of lipids, of the allosteric properties of the receptor protein in its detergent-soluble form.

Acetylcholine↗

[Evaluation of C3d in primitive chronic glomerular nephritis (author's transl)].

Plasma levels of C3d, which is liberated by enzymatic cleavage of C3, are determined in 97 patients with primitive chronic glomerular nephritis. This level is indicative of an abnormally high consumption of C3. In all cases where C3 is low, C3d is found at abnormally high levels. When the level of C3 is normal, C3d may, however, be elevated: a more subtle interpretation of the pathologic significance of C3 in immune disease is thus possible.

Complement C3↗

[Measurements of serum C3d in primitive chronic glomerular nephropathies (author's transl)].

Measurement of serum C3 does not provide precise informations concerning an eventual consumption of this complement component during an immunological process. An increased synthetic rate may compensate an accelerated catabolism. The study of breakdown products of C3, such as C3d is a more sensitive approach of the role of complement in some immunological disorders. Therefore C3d was measured in the serum of patients with chronic non systemic glomerular diseases. High values of serum C3d were found in all cases of hypocomplementemic glomerulonephritis. Circulating C3d was also increased to a lower extent, in patients with normocomplementemic nephritis such as minimal change disease, mesangial nephritis with IgA deposits and membraneoproliferative (type I) glomerulonephritis. The data suggested the involvement of complement in a number of glomerulonephritis. Participation of complement in immunological disorders particularly in chronic non systemic glomerulonephritis could require a reevaluation when functional tests are performed in addition to static measurements.

Complement C3↗