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Biomedical subjects

I H Lepow

Publications and source records attributed to I H Lepow.

At least 19 recordsLinked to original sources
PubMed1979

Host defense against Neisseria meningitidis requires a complement-dependent bactericidal activity.

Some individuals, with severe or recurrent infection with Neisseria species, have been identified as lacking a component in the terminal attack sequence of complement (complement components 5 to 9). The relevance of the terminal attack sequence to various phases of host defense was tested with the use of the C-11 strain of meningococci and human serum genetically deficient in complement component 8 (C8-D). The C8-D serum was comparable to normal serum in supporting ingestion and intracellular killing by leukocytes but was not bactericidal in the fluid phase unless reconstituted with C8. Thus, serum complement-dependent bactericidal activity may be especially critical for the host's defense against invasive Neisseria species.

Blood Bactericidal Activity↗
PubMed1976

Glomerulonephritis with mesangial deposits of IgA unassociated with systemic disease.

Typical features of IgA-associated nephritis were found in renal biopsies from 16 of 355 consecutive patients. Generalized segmental mesangial proliferation was noted in biopsies from most patients, and dense deposits were detected by electron microscopy in mesangial regions of approximately 50% of biopsies. Immunofluorescent studies showed IgA to be the predominant immunoglobulin in glomueruli; IgG was present in less than 50% of biopsies and IgM in only 12%. The serum IgA value was significantly increased (P les than 0.001) in 50% of patients and the mean IgA/IgG ratio was significantly increase (P less than 0.001) for the patient group as a whole, which suggests a selective increase in IgA. Mesangial deposits of C3 were present in 15 of 16 biopsies and properdin was noted in all biopsies tested; C4 was not demonstrated in any biopsy. This suggests activation of the alternative complement pathway. The results of this study support the concept that IgA-associated nephritis is a unique condition that in some patients gives rise to idiopathic recurrent hematuria. Although the prognosis is good in the majority of patients, the renal disease may progress.

Adolescent↗
PubMed1976

Multiple sedimenting species of properdin in human serum and interaction of purified properdin with the third component of complement.

Normal human serum subjected to sucrose density gradient analysis exhibited multiple sedimenting species of properdin antigen. Properdin antigen distribution was dependent on serum concentration, ionic strength, temperature, and the presence of C3, and was not dependent on the presence of divalent metal cations or blood coagulation. In mixtures of purified components, properdin sedimented heavier in the presence of C3, C3b, or C3c. Addition of factor B to mixtures containing C3 and properdin was without effect. These data provide insights into earlier discrepancies concerning the sedimentation behavior of partially purified properdin, indicate a propensity of some constituents of the alternative pathway to form protein-protein complexes, and suggest caution in interpretation of immunopathological studies in which properdin deposits are found in the presence of C3.

ABO Blood-Group System↗
PubMed1976

Structural features and biologic properties of fragments obtained by limited proteolysis of C3.

Limited proteolysis of the third component of human complement (C3) was performed by using trypsin and streptococcal proteinase and the digests were analyzed for biologic activity. Incubation of C3 with trypsin for 1 min yielded a peptide with smooth muscle-contracting activity but no chemotactic activity, whereas the digest obtained after 15 min of incubation had only chemotactic activity. The conversion of muscle contracting to chemotactic activity could be correlated with the time course of trypsin hydrolysis. Hydrolysis of C3 with streptococcal proteinase gave a digest demonstrating only chemotactic activity. Each digest was resolved on a Sephadex G-100 column and the fractions containing biologic activities were characterized. The amino acid composition of the trypsin fragments, despite having different biologic activities, was remarkably similar, although differences in NH2-terminal amino acids were demonstrable. The fragments obtained by digestion of C3 with the streptococcal proteinase had an amino acid composition different from the trypsin fragments and displayed marked heterogeneity of NH2-terminal residues. These results suggest that slight alterations in the primary structure of C3 fragments may yield significant changes in their biologic activities and that the structural requirements for chemotactic activity are not confined to a single peptide species.

Amino Acid Sequence↗
PubMed1976

Complement activation in semi-solid medium: Insolubilization of properdin and the third component of complement (C3) in agar gels.

Although the role of properdin in the alternative pathway of complement activation remains unclear, evidence has recently been obtained for the formation of complexes between properdin and other components, including C3. In this study such complexes have apparently been directly visualized. When normal human serum and properdin were allowed to diffuse toward each other in agar gel for 16 hr, a line of precipitation could be seen when stained with Coomassie brilliant blue. The reaction occured at pH 8.6 in 0.05 M Veronal buffer at room temperature but not under physiologic conditions of pH or tonicity. Like the alternative pathway, the reaction was Me++ dependent, occurred with C2- or C5-deficient or hypogammaglobulinemic serum, and did not occur with aged, 52 degrees C-inactivated, C3b inactivator-deficient, or C3-deficient serum. 125I-labeled C3 and properdin but not Factor B were incorporated in the precipitate. Eleven sera containing the C3 nephritic factor failed to produce a precipitate with properdin, but a line of precipitation occurred between seven of these sera and normal serum. This line showed identity with the line occurring between properdin and normal serum. The phenomenon appears to result from formation of insoluble complexes between proteins of the alternative pathway and agar.

Agar↗
PubMed1975

Metabolism of properdin in normal subjects and patients with renal disease.

Properdin deposition has been recognized in glomeruli of patients with acute and chronic nephritis and lupus nephritis, and low serum properdin levels have been found in these disorders. These findings suggest that properdin may be involved in the production of glomerular damage and that low properdin levels may be due to hypercatabolism. The study was designed to examine the metabolism of properdin in normal subjects and to look for an abnormality in five patients with systemic lupus erythematosus with renal involvement and in six patients with membranoproliferative glomerulonephritis or dense deposit disease (MPGN). Highly purified human properdin was prepared by elution from zymosan, followed by DEAE-cellulose and carboxymethyl-Sephadex chromatography, and labeled with 125I by the iodine monochloride method. Parameters of metabolism were determined by monitoring plasma and urinary radioactivity at frequent intervals after the intravenous injection of 1-2 muCi of labeled material. The fractional catabolic rate (FCR) of properdin in normal subjects was found to have a very narrow range of 0.78-1.0,% of the plasma pool per hour (mean 0.95%). In systemic lupus erythematosus, the FCR was regularly elevated with a range of 1.21-2.30% (mean 1.70%). In MPGN, FCR was elevated in three patients (1.22, 1.94, and 2.08%) and within or below the normal range in three (0.78, 1.00, and 1.00%). Properdin levels were reduced in two patients who had the highest FCR's noted in the study. Properdin synthetic rates in normals varied from 4.1 to 14.3 mug/kg per h (mean 9.1) and was not found to be reduced in any patient. Properdin catabolism was found to be normal in a patient deficient in the C3b inactivator. These studies show that properdin is hypercatabolized in patients with renal disease and that decreased properdin levels when they occur in these patients can be entirely explained on the basis of this hypercatabolism.

Adolescent↗
PubMed1973

The relationship of glycine-rich -glycoprotein to factor B in the properdin system and to the cobra factor-binding protein of huan serum.

Factor B activity of the properdin system was found to be identical with purified glycine-rich beta-glycoprotein (GBG) but was distinct from the normal human serum protein capable of forming a C3-inactivating complex with a protein from cobra venom (CoF). Factor B activity coincided with electrophoretically separated GBG genetic variants, whereas the CoF-binding protein did not. GBGase destroyed factor B as it cleaved GBG but did not destroy the C3-inactivating activity of the CoF-binding protein. During incubation of serum with CoF, GBG did not change in molecular size, nor was there any coincidence in the immunoelectrophoretic mobilities of CoF and GBG. It was not possible to precipitate labeled CoF incubated with serum by anti-GBG, nor labeled GBG from serum incubated with CoF by anti-CoF. The CoF-binding capacity of serum was 2 mg/100 ml or less or under 6.5% of the serum concentration of GBG. When labeled CoF was added to serum below the binding capacity, complete complexation of the CoF was demonstrated, whereas CoF was largely uncomplexed when CoF was added in amounts equimolar to GBG.

Animals↗