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Biomedical subjects

C A Alper

Publications and source records attributed to C A Alper.

At least 163 records · Page 9Linked to original sources
PubMed1978

Acute phase reactants ceruloplasmin and haptoglobin and their relationship to plasma prostaglandins in rabbits bearing the VS2 carcinoma.

Results of previous studies have shown that the VX2 carcinoma in rabbits synthesizes large amounts of prostaglandin E2 (PGE2). PGE2 secreted by the tumor is rapidly metabolized and can be measured in plasma as the metabolite 13,14-dihydro-15-keto-PGE2 (PGE2-M). We have previously proposed that the hypercalcemia that occurs in rabbits bearing the VX2 carcinoma is due to excessive secretion of PGE2 by the tumor and its subsequent action on the skeleton as a bone resorption-stimulating factor. In the course of these studies, we noted that the plasma of rabbits bearing the VS2 carcinoma became blue about 1 wk after tumor implantation. The intensity of the color increased markedly thereafter. We therefore measured ceruloplasmin in plasma by both chemical and immunological assay methods. Plasma ceruloplasmin and PGE2-M rose in parallel (within 7-10 days) and preceded by 7-10 days the development of hypercalcemia. 2 wk after tumor implantation, plasma PGE2-M and ceruloplasmin had risen about 20- and 6-fold, respectively, while the rise in plasma calcium was just beginning. Indomethacin, an inhibitor of prostaglandin synthesis, given from the time of tumor implantation prevented completely the hypercalcemia and largely inhibited the rise in ceruloplasmin. When given after hyperprostaglandinemia had developed, indomethacin produced a fall in both PGE2-M and ceruloplasmin. A rise in plasma haptoglobin concentrations similar to that seen for ceruloplasmin was also observed. No changes in plasma albumin concentrations occurred. We conclude that the acute phase reactants ceruloplasmin and haptoglobin rise rapidly in the plasma of rabbits bearing the VX2 carcinoma, and that this increase is related to arachidonic acid metabolism in these animals. It is possible that arachidonic acid metabolites also play a role in the elevations of these two plasma proteins observed in certain patients with malignant tumors.

Animals↗
PubMed1978

Inherited deficiency of the sixth component of complement: a silent or null gene.

Four families have been studied, some members of which have inherited deficiency of the sixth component of complement. The genetically determined electrophoretic variants of C6 were evaluated in all family members. Seven individuals were found who did not have the variant found in the serum of the parent from whom they inherited the deficiency. It is inferred that the isolated low levels of C6 in these individuals results from the heterozygous state of a normal C6 variant gene and a silent or null C6 gene; the genes determining electrophoretic variants and the low serum levels of C6 are allelic.

Alleles↗
PubMed1978

Evidence for a silent or null gene in hereditary C2 deficiency.

Three generations of a family with hereditary C2 deficiency were studied, Six members heterozygous for C2 deficiency were identified by serum C2 levels that were approximately 50% of normal C2 values and the identity was supported by HLA analysis. All six members with low C2 levels had only a single electrophoretic variant. Two of four children did not have the variant found in the parent from whom they inherited the partial C2 deficiency. It is inferred that the low levels of C2 result from the inheritance of a silent or null gene, C2D allelic with the structural genes controlling the electrophoretic variants.

Antigens↗
PubMed1977

Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex.

In an attempt to map the gene (or genes) controlling the synthesis fo the fourth component of complement (C4), we performed linkage studies in a family with hereditary C4 deficiency. The proband, a seven-year-old boy with lupus erythematosus, consistently lacked deteftable serum C4 by both functional and protein measurements. The complement defect was transmitted as an autosomal recessive disorder. Eight of 15 family members were considered to be heterozygotes, seven because of low C4 levels and one because of genetic data (obligate heterozygote). The gene (or genes) coding for C4 deficiency appeared to be linked to the major histocompatibility complex (A2,B12,DW2 on the maternal side and A2,BW15,LD108 on the paternal side) and to other markers known to be in close proximity to the histocompatibility complex on chromosome 6 (phosphoglucomutase-3, glyoxalase-1 and properdin factor B).

Child, Preschool↗
PubMed1977

Heterogeneity of nephritic factor and its identification as an immunoglobulin.

Complement C3 nephritic factor (NeF) produces alternative pathway-meciated C3 cleavage by binding to and stabilizing the alternative pathway C3 convertase, C3bBb. Some studies have suggested that NeF is an immunoglobulin, while others conclude that it is a distinct serum protein. The heterogeneity of NeF was evaluated by electrophoresis and isoelectric focusing of NeF-containing serum followed by hemolytic demonstration of NeF activity in agar gel. With each method, diffuse cathodal zones or multiple bands of hemolysis developed, which revealed remarkable variations in patterns from patient to patient. NeF activity was absorbed by and eluted from insolubilized antibody to Fc and Fab fragments of IgG. Immunoabsorption of six NeF-containing sera with insolubilized anti-kappa and anti-lambda light chain antisera revealed that NeF had kappa antigenic determinants in three, lambda antigenic determinants in one, and both kappa and lambda antigenic determinants in two. These data indicate that NeF is an oligoclonal immunoglobulin. Because NeF binds to the alternative pathway C3 convertase, C3bBb, we suggest that it is an antibody to a conformational antigen of the C3-factor B complex, and thereby stabilizes this complex.

Complement C3↗
PubMed1977

Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans.

Human monocytes synthesized the third component of complement (C3) up to 5 wk in vitro. Evidence for net C3 synthesis was based on (a) incorporation of 14C-labeled amino acids into C3 protein, (b) indentity of the allotype of C3 produced in vitro with that of the doner's serum C3, even in the presence of carrier C3 protein of a different allotype; (c) correspondence of electrophoretic mobility, size, and subunit structure of C3 protein produced in vitro with serum C3; (d) inhibition of C3 production with cycloheximide. Monocytes from two unrelated C3-deficient patients were studied under conditions that supported C3 synthesis by normal monocytes. Serum from each of the patients contained less than 1% of the normal C3 concentration, buth their monocytes produced C3 at approximately equal to 25% of the normal rate when studied after 2 wk in vitro. The C3 produced in vitro by monocytes from one of the patients had the molecular weight of normal serum C3 and dissociated appropriately under reducing conditions. Monocytes from C3-deficient patients could not be distinguished from normals on the basis of morphology, rosetting with C3-coated erythrocytes, or rates of C2, and total protein synthesis.

Blood Proteins↗
PubMed1977

Genetic polymorphism of the sixth component of complement (C6) in the rhesus monkey.

With isoelectric focusing, the complement protein C6 has been shown to be genetically polymorphic in the rhesus monkey. Three codominant alleles of a single autosomal locus, Rh C6, have been recognized: C6A, C6B, and C6R, with gene frequencies of 0.592, 0.354, and 0.053 in a random rhesus monkey population. Hardy-Weinberg analysis of the phenotypic frequencies in this population yielded observed values very close to those expected. Both natural mating between individuals carrying the various alleles and artificial combinations of sera of the different C6 types demonstrate patterns consistent with this model. Analysis of several families of monkeys confirmed the Mendelian autosomal codominant inheritance with numbers of offspring very close to expected values and no offspring types inconsistent with the mating pair types.

Animals↗
PubMed1977

Complement activation in semisolid media: insolubilization of alternative pathway convertases in agar gels with C3 nephritic factor-containing sera.

It was previously shown that when normal human serum and purified properdin or serum containing nephritic factor were allowed to diffuse toward each other in agar, a stainable precipitin line formed only in the presence of an intact alternative pathway. In the present study we have shown that when guinea pig erythrocytes were incorporated in agar and normal human serum was allowed to diffuse toward C3 nephritic factor-containing serum, a line of hemolysis appeared that coincided with the stainable line. The line of hemolysis only formed in the presence of C3, factor B and Mg++, as does the properdin or C3 nephritic factor-induced stainable line. When C2-deficient serum was incorporated in agar with guinea pig erythrocytes and serum samples containing nephritic factor were applied in wells, rings of lysis developed, the areas of which correlated significantly with nephritic factor activity. When partially purified nephritic factor (contaminated only with IgG) or serum containing nephritic factor was subjected to electrophoresis in agar-guinea pig erythrocyte gels and overlaid with normal human serum, bands of lysis developed that required factor B and C3. Lysis of guinea pig erythrocytes in this system appears to be due to insolubilization of alternative pathway convertases with activation of the membrane attack unit C5-C9.

Complement C3↗
PubMed1976

Inherited structural polymorphism in human C2: evidence for genetic linkage between C2 and Bf.

Structural variation in the second component of human complement was identified in about 4% of serum samples from random unrelated individuals of all the major races. Three forms of C2 have been identified by isoelectric focusing in polyacrylamide gel and development of patterns in agarose gel containing antibody-sensitized sheep red cells and C2-deficient serum: C2 C (common), C2 A (acidic), and C2 B (basic). The C2 variants were shown to be inherited as autosomal codominant traits, and suggestive evidence for close linkage between C2 and Bf was obtained.

Complement C2↗
PubMed1976

Cobra venom factor: evidence for its being altered cobra C3 (the third component of complement).

Evidence is presented that cobra venom factor, the anticomplementary protein in Naja naja venom, is modified cobra C3 (the third component of complement). Antiserum to the cobra venom factor cross reacts with human C3. A protein in cobra serum reacts strongly with antiserum to the venom factor and the former protein, like human C3, is converted by incubation of cobra serum with endotoxin, hydrazine, or simple storage at 37 degrees C. Incubation of cobra venom factor with cobra serum destroys the C3 cleaving activity of the venom factor in human serum, whereas human C3b inactivator is ineffective. Thus, the cobra venom factor appears to be a form of C3 (perhaps C3b); its potent action in human serum probably derives from its lack of sensitivity to human C3b inactivator.

Animals↗
PubMed1976

Homozygous human C3 deficiency. The role of C3 in antibody production, C-1s-induced vasopermeability, and cobra venom-induced passive hemolysis.

Studies of the family of a patient with marked deficiency of the third component of complement (C3) demonstrated that the patient was homozygous for a blank allele at the C3 locus, C3-. Metabolic studies with purified radiolabeled C3 in the patient revealed a mildly elevated fractional catabolic rate and a markedly reduced synthesis rate, consistent with a lack of C3 synthesis as the patient's primary defect. There was also a mild increase in the rate of conversion of purified C3 added to her serum and incubated at 37 degrees C in vitro. Major blood group-compatible erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria had the same shortened survival in the C3-deficient patient as in a normal control. Although no leukocytosis developed in the patient in spontaneous infection by pyogenic organisms, there was a normal leukocytosis in response to the injection of thyphoid vaccine. The intradermal injection of C-1s, which produces a marked increase in vasopermeability in the skin of normal subjects, produced no definite change in the patient, possibly implicating C3 or a protein in the alternative pathway as the normal mediator of this response. The patient's serum exhibited near-normal immune adherence activity, confirming the lack of requirement of C3 for this function. C5 inactivation and passive hemolysis of unsensitized guinea pig erythrocytes occurred normally in C3-deficient serum on incubation with cobra venom factor, indicating that C3 is not required for these reactions. The patient's humoral antibody response to both protein and carbohydrate antigens was entirely normal, making it unlikely that C3 is required for antigen processing.

Alleles↗
PubMed1976

The chromosomal order of genes controlling the major histocompatibility complex, properdin factor B, and deficiency of the second component of complement.

The relationship of the genes coding for HLA to those coding for properdin Factor B allotypes and for deficiency of the second component of complement (C2) was studied in families of patients with connective tissue disorders. Patients were selected because they were heterozygous or homozygous for C2 deficiency. 12 families with 15 matings informative for C2 deficiency were found. Of 57 informative meioses, two crossovers were noted between the C2 deficiency gene and the HLA-B gene, with a recombinant fraction of 0.035. A lod score of 13 was calculated for linkage between C2 deficiency and HLA-B at a maximum likelihood value of the recombinant fraction of 0.04. 18 families with 21 informative matings for both properdin Factor B allotype and HLA-B were found. Of 72 informative meioses, three recombinants were found, giving a recombinant fraction of 0.042. A lod score of 16 between HLA-B and Factor B allotypes was calculated at a maximum likelihood value of the recombinant fraction of 0.04. A crossover was shown to have occurred between genes for Factor B and HLA-D, in which HLA-D segregared with HLA-A and B. These studies suggest that the genes for Factor B and C2 deficiency are located outside those for HLA, that the order of genese is HLA-A, -B, -D, Factor B allotype, C2 deficiency, that the genes coding for C2 deficiency and Factor B allotypes are approximately 3--5 centimorgans from the HLA-A and HLA-B loci, and that the apparent lack of recombinants between the Factor B gene and C2 deficiency gene suggests that these two genes lie in close proximity to one another.

Chromosome Mapping↗