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Biomedical subjects

M R Klemperer

Publications and source records attributed to M R Klemperer.

36 records · Page 2Linked to original sources
PubMed1975

Contrasting splenic mechanisms in the blood clearance of red blood cells and colloidal particles.

We have studied the blood clearance and organ uptake of colloidal particles and of antibody-coated and chemically treated Na2 51Cr O4-labeled erythrocytes (RBC) in mice. Hepatic and splenic uptake of both colloidal particles and autologous RBC coated with rabbit antibody were reduced significantly following pretreatment of animals with cortisone acetate. Hepatic removal of RBC previously treated in vitro with N-ethyl-maleimide (NEM) or phenylhydrazine-HCl (PHZ) was similarly depressed by pretreatment with cortisone. In contrast, the splenic uptake of NEM- and PHZ-altered erythrocytes was unaffected by cortisone. Scanning and transmission electron microscopic examination of perfused spleens from PHZ-injected animals demonstrated extensive mechanical trapping of Heinz body-containing RBC in sinus wall apertures, whereas little erythrophagocytosis was observed. These studies suggested that, while clearance of inert particulate matter and of antibody-coated RBC from the blood occurred primarily by a cortisone-suppressible, presumably phagocytic process in the spleen, chemically altered RBC were removed primarily by a cortisone-insensitive filtration process in the splenic microvasculature.

Animals↗
PubMed1975

Hereditary C6 deficiency in man.

An 18-year-old black female (D.B.) in good general health was found to have no hemolytic activity in serum CH50 titrations. Functional assays yielded normal values for all C components except C6. C6 was not detectable in plasma or serum by two different functional assays nor by antigenic analysis using monospecific anti-C6 antibody. Hemolytic activity was restored by addition of functionally pure C6. By specific functional assay, both parents and 5 of 6 available sibs had approximately half-normal serum C6 levels and 1 sib was normal. Biologic properties of D.B. serum include: a) absent bactericidal activity against S. typhi 0 901 with or without added rabbit antibody; b) normal generation of chemotactic activity for human neutrophils in the presence of endotoxin or aggregated IgG; c) ability to sensitize appropriate cells for immune adherence of agglutination by anti-C3 Coombs serum; and d) inability to lyse PNH red cells in either acid hemolysis or "sugar water" tests. An extensive clotting workup by standard methods was within normal limits. These studies document for the first time a human kindred with C6 deficiency. This defect exhibits a classic mendelian autosomal inheritance, with all 3 genotypes being recognizable. Unlike the C6-deficient rabbits studied by others, the homozygous C6-deficient human exhibits chemotactic and coagulation functions within the range of normal.

Adolescent↗
PubMed1974

Hereditary deficiency of the sixth component of complement in man. I. Immunochemical, biologic, and family studies.

An 18-yr-old black woman in good general health was found to lack serum hemolytic complement activity. The sixth component of complement (C6) was undetectable by functional assay of serum or plasma and by immunoprecipitin analysis of serum. Functional titers of all other complement components were normal. The absence of C6 in the patient's serum could not be accounted for by a circulating C6 inhibitor, and addition of functionally pure C6 to the patient's serum restored hemolytic activity to normal. Both parents of the proband and five of six available siblings had approximately half the normal levels of functional C6. The other sibling had a normal C6 level. These data suggest that both parents and five siblings are heterozygous for C6 deficiency, while the proband is homozygous and one sibling is normal. Thus, C6 deficiency appears to follow classic mendelian inheritance, with all three possible genotypes recognizable within the family. Functional properties of the proband's C6-deficient serum included total absence of bactericidal activity against Salmonella typhi 0 901 and Hemophilus influenzae, type b, and inability to mediate lysis of red blood cells from patients with paroxysmal nocturnal hemoglobinuria in either the acidified serum or "sugar water" tests. The proband's serum did, however, exhibit a normal capacity (a) to generate chemotactic activity during incubation with bacterial endotoxin or aggregated IgG, (b) to mediate the immune adherence phenomenon, and (c) to coat human red blood cells, sensitized by cold agglutinins, with C4 and C3.

Adolescent↗
PubMed1974

Hereditary deficiency of the sixth component of complement in man. II. Studies of hemostasis.

Prompted by previous observations of defective blood clotting in rabbits deficient in the sixth component of complement (C6), an evaluation was made of the hemostatic functions of the homozygous proband of a newly recognized human kindred with hereditary C6 deficiency. This human subject, who had no clinical evidence of a bleeding disorder, exhibited a total lack of C6 by functional and immunoprecipitin assays of serum or plasma. Standard tests of hemostatic function were normal; however, when the whole blood clotting time was measured at 25 degrees C in plastic tubes, it was at the upper range of our normal values. In confirmation of this observation, prothrombin consumption, when performed at 37 degrees C in plastic tubes, was at the lower range of normal. Inulin and endotoxin, in concentrations shown to cause activation of human complement, had little or no effect on clotting times or prothrombin consumption of normal or C6-deficient human blood. These observations indicate that absence of C6 does not have a significant effect on hemostatic function in man. In the light of other investigations, the observed differences in clotting function between C6-deficient human blood and C6-deficient rabbit blood could be due to species differences governing the susceptibility of platelets to complement activation.

Complement C6↗
PubMed1971

Genetically determined heterogeneity of the C1 esterase inhibitor in patients with hereditary angioneurotic edema.

Normal human serum contains 18 +/-5 mg/100 ml of C1 esterase inhibitor (alpha-2 neuraminoglycoprotein) as estimated by immunochemical means. Of 118 patients with hereditary angioneurotic edema, the sera of 80, from 42 kindred, contained a mean concentration of 3.15 mg/100 ml or 17.5% of normal. The mean serum concentration in 35 patients in 7 other kindred was 20 mg/100 ml or 111% of normal, and 3 patients in another kindred contained over 80 mg/100 ml or greater than 400% of normal. The nonfunctional inhibitors in patients' sera of these eight kindred were identical with normal C1 esterase inhibitor by Ouchterlony analysis, but they were different from normal and from each other with respect to their electrophoretic mobility, their capacity to bind C1 esterase, and their ability to inhibit esterolysis of N-acetyl-tyrosine-ethylester.

Acetates↗
PubMed1969

The enhancement of bacterial phagocytosis by serum. The role of complement components and two cofactors.

The role of serum factors in the phagocytosis of pneumococci was studied employing a spectrophotometric assay which measures reduced nitro blue tetrazolium (NBT) dye. Dye reduction occurs within the phagocyte shortly after bacterial ingestion as measured by the phagocytic index technique and by the uptake of (125)I-pneumococci. Bacteria prepared with gammaG antibody were not phagocytosed unless a small volume of fresh normal serum was added. Using fresh sera deficient in single complement components, it was demonstrated that the first four components are necessary for optimal bacterial phagocytosis. When highly purified complement components were added to the antibody-coated pneumococci, enhancement of phagocytosis was achieved only with the sequential addition of C1, C4, C2, and C3. Evidence has been presented that human C3 bound to an immune complex exhibits peptidase activity and that this activity is essential for phagocytosis. A heat-labile, dialyzable serum cofactor which enhances C3 peptidase activity enhanced the phagocytosis of pneumococci prepared with purified complement components. A second phagocytosis-promoting cofactor, which is not a complement component, was found to be a heat-labile, 5-6S, beta pseudoglobulin. This protein may stabilize C3 peptidase activity or inhibit enzymatic inactivation of C3.

Blood Proteins↗
PubMed1969

Inherited deficiency of the third component of human complement (C'3).

A kindred has been investigated in which seven individuals were found to have half-normal serum concentrations of the third component of complement (C'3). This partial deficiency was transmitted as an autosomal dominant trait. Affected individuals were entirely healthy. Hemolytic complement titers were slightly reduced but immune adherence titers and reagent titrations of the classical complement components were normal.Examination for C'3 allotypes revealed that all affected individuals had patterns resembling those of homozygotes. Analysis of the inheritance of C'3 structural genes disclosed that the most likely mechanism for partial C'3 deficiency in this family was nonexpression of one allele.

Blood Protein Electrophoresis↗
PubMed1968

Effect of C'1 esterase on vascular permeability in man: studies in normal and complement-deficient individuals and in patients with hereditary angioneurotic edema.

When purified human C'1 esterase is injected intradermally in man, increased vascular permeability results. This effect is not blocked by soybean trypsin inhibitor and is not abolished by pretreatment with the antihistamine, pyribenzamine, or by compound 48/80. Thus, the effect is not due to the release of endogenous histamine. The decreased permeability response of individuals with a specific hereditary deficiency of C'2 is evidence for the complement-dependent nature of this reaction. The apparently normal response to intradermal C'1 esterase developed by individuals with an acquired specific deficiency of C'3 suggests that the vasoactive substance may be derived from one of the early reacting complement components. Characteristic attacks of angioedema have been provoked by the intradermal injection of human C'1 esterase in two individuals with hereditary angioneurotic edema. Patients with hereditary angioneurotic edema are unresponsive to intradermal injections of C'1 esterase immediately after attacks.

Adult↗