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Biomedical subjects

A T Sobel

Publications and source records attributed to A T Sobel.

17 recordsLinked to original sources
PubMed1984

Silent lupus nephritis among patients with discoid lupus erythematosus.

A kidney biopsy was performed in 7 hypocomplementemic discoid lupus erythematosus patients despite the absence of overt renal involvement. Five patients had glomerular immune deposits and 2 patients with disseminated discoid lupus erythematosus exhibited definite proliferative glomerulonephritis. Those findings show that silent lupus nephritis may be encountered in discoid as well as in systemic lupus erythematosus, providing additional evidence supporting the unity of the disease. We suggest that hypocomplementemic patients with discoid lupus erythematosus must be carefully screened for renal disease by periodic urinalysis examinations.

Complement C3↗
PubMed1983

[Experimental prevention of a hemolytic disease of the fetus with F (ab)'2 immunoglobulin fragments].

An experimental study was designed to tentatively protect fetal red blood cells (RBC) against hemolysis by covering fetal RBC antigenic sites with F (ab)'2 fragments of hemolysing antibodies. Sheep antibodies were raised against rabbit RBC. IgG were separated and part of the IgG pool subjected to pepsin digestion, in order to isolate F (ab)'2 fragments. Near term rabbit fetuses were injected through the uterine wall with either IgG, F (ab)'2 or successively F (ab)'2 then IgG. Fetuses were extracted by hysterotomy, one hour after the last injection. Neonatal blood was collected by cardiac puncture for hematocrit determination and detection of hemolysis. Among fetuses injected with IgG alone, nine were deal at hysterotomy and evidenced diffuse hemorrhagic syndrome. Six were born alive with hemolysis, including three with severe anemia. (Ht = 26%). Nine fetuses successively injected with F (ab)'2 and then IgG, were all born alive with normal hematocrits (Ht = 43%). The protective role of F (ab)'2 fragments and their potential therapeutic use are discussed.

Animals↗
PubMed1982

[Kidneys; hypertension and pregnancy. III. The renal risk in pregnancy].

When a woman with chronic renal disease wishes to become pregnant, the risk to the mother and the foetus is often inaccurately evaluated or exaggerated. In patients with primary nephropathy the foetal risk is significantly increased by the arterial hypertension frequently associated with renal insufficiency. In systemic lupus erythematosus (SLE) with renal involvement, the risk represented by hypertension is compounded by a high incidence of spontaneous abortion, particularly when the disease is progressive. Pregnancy seems to have little influence on SLE itself, and the classical post-partum problems are controversial. Much more dangerous are acute complications, such as cortical necrosis or haemolytic and uraemic syndromes occurring in apparently healthy women during the last trimester of pregnancy and after delivery. Urinary infections are common during pregnancy. They are heralded by asymptomatic bacteriuria which should be systematically detected, since these infections increase the likelihood of pyelonephritis with in turn increases the severity of perinatal complications.

Acute Kidney Injury↗
PubMed1982

[Kidneys, hypertension and pregnancy. II. Hypertension in pregnancy: significance, prognosis, and treatment (author's transl)].

A rise in arterial pressure above 140 mmHg systolic or 85 mmHg diastolic is pathological in pregnant women. Such changes may either reveal chronic hypertension or constitute a purely gestational complication. The persistence or regression of abnormally high BP values 3 months after delivery retrospectively indicates whether the hypertension was chronic or pregnancy-related. When BP values are very high (diastolic above 110 mmHg) the mother is exposed to vascular accidents and the most effective anti-hypertensive drugs are required. In the more common moderate hypertension, both the mother (eclampsia) and the foetus (intra-uterine or neonatal death, low birth-weight) are at risk. The risk is better predicted by proteinuria and hyperuricaemia than by the BP values themselves, and whether anti-hypertensive drugs are warranted is uncertain. Studied comparing patients with treated and untreated moderate hypertension have yielded two valuable results: (1) methyldopa administered to the mother is harmless to the foetus, and (2) abortion during the second trimester of pregnancy is probably prevented when methyldopa is prescribed against chronic hypertension. No study has yet afforded evidence that the use of anti-hypertensive drugs in gestational hypertension benefits the foetus. Further therapeutic trials and a better knowledge of the natural history and mechanisms of hypertension in pregnancy are required before adequate management of this condition can be determined.

Antihypertensive Agents↗
PubMed1982

[Kidneys, hypertension and pregnancy. I. Renal function in normal pregnancy (author's transl)].

Pregnancy enhances renal functioning. As early as the first week of amenorrhoea, renal plasma flow (RPF) and glomerular filtration rate (GFR) increase by 30 to 50%, with parallel rise in creatinine and urea clearances. The water and salt balance becomes strongly positive. However, the normal mechanisms of NaCl retention (aldosterone, desoxycorticosterone, oestrogens) remain active, counterbalancing the natriuretic effects of progesterone and of increased filtered sodium load. Renal regulation of the acid/base equilibrium is preserved, albeit adjusted to a higher pH threshold. At the beginning of pregnancy uric acid clearance is increased and tubular reabsorption of glucose is decreased. Blood pressure falls by 20 mmHg during the first semester. Prostaglandins and progesterone oppose the vasopressive action of angiotensin in pregnant women, and changes in their metabolism may account for the development of pre-eclampsia.

Blood Pressure↗
PubMed1982

Impaired IgG synthesis in patients with the nephrotic syndrome.

Immunoglobulin synthesis by pokeweed mitogen-stimulated lymphocytes from 62 nephrotic patients and 18 healthy controls was studied. Defective IgG production was observed in patients with the nephrotic syndrome related to minimal change disease, mebranous glomerulonephritis and membranoproliferative glomerulonephritis. The mean values of in vitro IgG synthesis were 20%, 61% and 32%, respectively, of that obtained in the control group. At the same time, serum IgG levels were significantly decreased in each group of patients. In minimal change disease, reduced IgG production and serum levels were fully reversible after recovery (off steroid therapy). The data indicate that a cellular defect of antibody production is a common and eventually transitory phenomenon associated with the acquired hypogammaglobulinemia found in patients with a variety of glomerulopathies.

Adult↗
PubMed1981

Quantitation of C2 by rocket immunoelectrophoresis in 120 pathological sera.

A potent monospecific anti-C2 was used for quantitation of serum C2 by rocket immunoelectrophoresis (RIE). This ready procedure was compared to the one-step hemolytic titration utilizing C2-deficient human serum. RIE detected 4 nanograms C2 in 5 microliters samples. Using highly purified C2 as a reference, C2 concentration in pooled normal human sera was estimated around 50 micrograms/ml by both test systems. The reliability of RIE was assessed when immunochemical and hemolytic determinations were comparatively performed in 120 pathological sera. The correlation coefficient was significant (r = 0.69) and only 8 sera were found outside the expected range, exhibiting an abnormally high C2 protein. They were obtained from 6 patients with cryoglobulinemia associated connective tissue disease and 2 with acute glomerulonephritis. These occasional findings suggested the possibility of an activation of C2 hemolytic activity without simultaneous loss of C2 protein. In 16 sera of individuals with familial C2 deficiency (r = 0.83) and 29 sera of patients with angioneurotic edema (r = 0.72), RIE provided an extremely simple and reliable alternative to the time consuming hemolytic titration of C2.

Animals↗
PubMed1981

Serum and cerebrospinal fluid C2 in multiple sclerosis.

C2 hemolytic activity was quantitated in the serum and cerebrospinal fluid of 46 MS patients studied twice at a 1-year interval. whereas serum C2 levels were found within the normal range, CSF C2 values were decreased (55 and 59% of normal) in patients with severe active disease. In contrast CSF C2 levels were normal in patients with stable or recently improved condition. CSF C2 fluctuations in individuals were found to closely parallel changes in the clinical course.

Complement C2↗
PubMed1979

A rosette assay for the determination of C 1 q receptor-bearing cells.

A rosette assay for the identification of cells with receptors for C 1 q is described. Glutaraldehyde-treated bovine erythrocytes bound C 1 q specifically, and the reagent thus prepared provided a valid indicator for rosette formation mediated by C 1 q receptors. The presence of these receptors on the membrane of a subset of human peripheral lymphocytes (mainly non-G cells) and on B-derived lymphoblastoid cells was confirmed. Rosette formation was dependent on the number of C 1 q molecules bound per indicator cell and was specifically inhibited by soluble native C 1 q and pepsin-resistant C 1 q fragments. These data, together with the reduced binding activity of C 1 r-C 1 s-associated C 1 q, indicated that the C 1 q binding sites for lymphoid membranes are expressed on the collagen-like moiety, C 1 q rosette formation provided a simple new procedure for fractionation of human lymphocyte populations and separation from phagocytes that do not express receptors for C 1 q.

Animals↗
PubMed1979

Hereditary C2 deficiency associated with non-systemic glomerulonephritis.

A patient with non-systemic idiopathic glomerulonephritis was found to have a complete deficiency of C2, the second component of complement. The clinical course, histological findings and serological abnormalities are reported in detail. The renal disease was a mild glomerulonephritis with mesangial and subendothelial immune deposits comprising IgG, IgM and C3, increased mesangial matrix without significant cell proliferation. An immunogenetic analysis of the patient's family was carried out. It was demonstrated that the homozygous C2 deficiency was associated with heterozygotism for HLA-A, B and D. Only one of the C2 deficient genes was associated with the expected HLA-A10, B18 haplotype and the propositus was HLA-D2 negative. This report confirms the fact that non-systemic glomerulonephritis should be included in the variety of immunological disorders associated with a complement deficient state. However, C2 deficiency does not seem to be related specifically to a given histological variety of glomerulonephritis.

Adult↗
PubMed1979

Activation of the classical complement pathway by nephritic factor bound to the alternative pathway C3/C5 convertase.

Nephritic Factor (NF), the potent alternative pathway activator, which is occasionally found in association with certain types of nephritis has recently been identified as an IgG class autoantibody specific for the C3 convertase (C3bB) of the alternative pathway. In these studies we have examined the possibility that the cell-bound NF-stabilized C3 convertase (EC3 bBNF) binds and activates the first component of the classical pathway of complement. EC3bBNF bound C1q, and the extent of binding was dependent upon the number of NF molecules bound per cell and decreased parallel to the dissociation and release of NF from the cells. Interaction of C1 with bound NF resulted in its activation as shown by the proteolytic conversion of proenzyme C1s to its activated form C1s. As was the case with C1q binding, C1 activation was dependent on the number of NF molecules bound per cell. Thus the NF-stabilized C3 convertase binds and activates C1.

Binding Sites↗
PubMed1978

The second component of complement (C2) as an index of hereditary angioneurotic edema.

Measurements of C2 hemolytic activity were performed in the sera of 13 patients with Hereditary Angioneurotic Edema. Prior to treatment, C2 values correlated with the severity of the disease in each patient. During androgen therapy with Danazol, C2 measurements reflected the clinical benefit of the drug more accurately than C4 levels, thus explaining the effectiveness of low drug doses. This study also suggests that breakdown products of C2 may play an essential role in the pathogenesis of the edema.

Angioedema↗
PubMed1977

Physicochemical characterization of a vascular permeability factor produced by con A-stimulated human lymphocytes.

Stimulation of human lymphocytes with Con A resulted in the liberation of a soluble lymphokine that increased the permeability of guinea pig skin capillaries. This factor, termed vascular permeability factor (VPF), was characterized by physicochemical methods. Upon gel filtration chromatography on Sephadex G-100, it eluted in a narrow peak with an apparent molecular weight of 12,000 daltons. The sedimentation rate of VPF, estimated by sucrose density gradient ultracentrifugation, was 1.8 S. Polyacrylamide gel electrophoresis showed the biologic activity to migrate in the beta region; the factor displayed a pI of 6.4 upon isoelectric focusing. These characteristics allow VPF to be distinguished from other human lymphokines.

Capillary Permeability↗
PubMed1976

[Association of monoclonal gammopathy with chronic glomerulonephritis and autoimmune hyperlipemia. Course of disease during therapy].

A case of benign monoclonal gammapathy associated with an auto-immune hyperlipidaemia and a chronic glomerulopathy is reported. Extraction of the monoclonal immunoglobulin made it possible to demonstrate its anti-lipoprotein antibody activity. Parallel changes in serum lipid levels and monoclonal immunoglobulin levels under the influence of melphalan confirmed the direction relationship between the lipid and protein disorders. The pathogenesis of the glomerulopathy and of the massive and prolonged activation of the classical complement pathway is more difficult to affirm. It is nevertheless possible that the renal involvement is due to an auto-immune complex disease.

Adult↗
PubMed1975

C1q deviation test for the detection of immune complexes, aggregates of IgG, and bacterial products in human serum.

This report describes a new, rapid, sensitive, and quantitative method for the detection of immune complexes, endotoxins, and other complement activating materials in patients sera utilizing the ability of these substances to react with isolated C1q. The procedure is based on the inhibition of radiolabeled C1q binding to sensitized sheep erythrocytes by C1q-reactive substances in pathological sera. The C1q deviation test may be performed on 50 mu1 of serum, using 1 mug of radiolabeled C1q per sample. The procedure may be completed in 1.5-2 h, it is capable of detecting 5 mug of aggregated human IgG per ml of serum, and its coefficient of variation is 4.2%. Application of the test to the study of 193 sera from 43 patients with Dengue hemorrhagic fever showed a positive correlation between degree of C1q deviation and severity of disease.

Antigen-Antibody Complex↗
PubMed1974

Receptor for the fourth component of complement on human B lymphocytes and cultured human lymphoblastoid cells.

This report describes receptors for C4b on human peripheral B lymphocytes. The simultaneous presence of C3b and C4b receptors on the same lymphocytes was demonstrated by the formation of mixed rosettes consisting of the lymphocytes, EAC14 and EAC1423. Furthermore, reduction of the number of EAC1423 rosette-forming lymphocytes in a lymphocyte population by albumin gradient centrifugation concomitantly reduced EAC14 rosette-forming lymphocytes. Binding of EAC14 intermediates to receptors on human lymphocytes and erythrocytes could be inhibited by equal amounts of soluble C3b or C4b, suggesting the presence of a single receptor for both ligands on those cells. In contrast, the results of the rosette assay with Raji cells, cultured human lymphoblastoid cells, EAC14 and EAC1423 suggested that the receptors for C4b and C3b are distinct entities, since Raji cells formed rosettes with EAC1423, but not with EAC14. Moreover, this report demonstrates a cooperation of erythrocyte-bound C4b and C3b in the binding of EAC1423 to B lymphocytes. In contrast to KAF-treated C3b, KAF-treated C4b did not bind to B lymphocytes, indicating that these cells lack a receptor for C4d.

Antigen-Antibody Complex↗