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Biomedical subjects

D S Chudwin

Publications and source records attributed to D S Chudwin.

At least 19 recordsLinked to original sources
PubMed1994

Activation of the alternative complement pathway by red blood cells from patients with sickle cell disease.

Increased activation of the alternative pathway of complement in serum from sickle cell disease (SCD) patients has been reported. We now show that this selective activation is not an artifact of clotting by measuring increased plasma concentrations of Bb in sickle cell patients compared to controls. Furthermore, we show that red blood cells (RBC) from SCD patients activate the alternative complement pathway more than control RBC in an in vitro system. RBC were incubated in 50% normal human serum chelated with 3.5 mM MgCl2 and 10 mM EGTA to block activation by the classical pathway, but allow alternative pathway activation. SCD RBC yielded significantly more activation, as measured by an EIA for C3, P complexes, than control RBC. Denser SCD RBC produced more activation than control RBC, unfractionated SCD RBC, and less dense SCD RBC. These findings are consistent with the hypothesis that dense irreversibly sickled cells, or membrane spicules or vesicles derived from them, may result in complement activation.

Anemia, Sickle Cell↗
PubMed1989

Prophylaxis and treatment of pneumococcal bacteremia by immune globulin intravenous in a mouse model.

A mouse model was developed to test the efficacy of human immune globulin intravenous (IGIV) in prevention and treatment of pneumococcal bacteremia. Mice pretreated with IGIV and then challenged with types 3 or 7F Streptococcus pneumoniae had significantly increased (P less than 0.025) survival compared to controls. Three commercially available IGIV preparations were all effective in significantly increasing (P less than 0.025) survival in mice already infected. Mice treated with IGIV plus penicillin had significantly greater (P less than 0.05) survival than those who received penicillin alone. IGIV may be useful in treatment of pneumococcal bacteremia.

Animals↗
PubMed1988

The terminal complement complex, C5b-9, a marker of disease activity in patients with systemic lupus erythematosus.

Concentrations of the terminal complement complex (TCC), C5b-9, were examined in 120 serum samples from 28 patients with systemic lupus erythematosus. Eleven patients with various manifestations of the disease were followed longitudinally for a 2-year period during active and inactive phases of the disease. In 9 of the 11 patients, elevations in TCC concentrations correlated with disease exacerbations. In many of these patients, C3 and C4 levels remained normal during the study and were less sensitive indicators of disease activity than were TCC concentrations. We believe that measurements of TCC are useful in monitoring patients with rheumatic diseases in which complement activation is a component.

Adult↗
PubMed1988

Complement activation in sickle cell disease: a liposome model.

Patients with sickle cell disease (SCD) have poorly defined abnormalities of their alternative complement pathway (ACP). We have previously shown chronic activation of the ACP in these patients. To determine the mechanism of this finding, we studied concentrations of the complement control proteins factors I and H in serum from patients with SCD and found no significant difference when they were compared with a control population. Because certain membrane surfaces promote ACP activation and changes occur in erythrocyte membrane phospholipid organization with sickling, we used a liposome model to determine whether ACP activation could be caused by abnormal phospholipid organization of sickle cells. Liposomes with the composition of the sickle cell outer leaflet, which is enriched in phosphatidylserine and phosphatidylethanolamine, activated the ACP significantly more than liposomes with normal outer leaflet phospholipid content. Similarly, liposomes with the composition of the erythrocyte inner membrane leaflet, containing large amounts of phosphatidylethanolamine and phosphatidylserine, activated the ACP more than liposomes with the phospholipid content of the outer leaflet. These findings suggest that phospholipid composition of membranes may play a role in their ability to promote ACP activation, and that changes in phospholipid organization in sickle cells may contribute to the chronic ACP activation observed in patients with SCD.

Anemia, Sickle Cell↗
PubMed1987

Correlation of serum HIV antigen and antibody with clinical status in HIV-infected patients.

An enzyme immunoassay (EIA) has been developed which detects antigen(s) (Ag) of the human immunodeficiency virus (HIV) in the serum of patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and patients at high risk for HIV infection. The test has a sensitivity of approximately 50 pg/ml of HIV protein. The specificity of the assay was determined with various virus infected cell lines, normal human sera/plasma, and serum from patients not known to be at risk for HIV infection. No false-positive HIV-Ag results were seen. Sera from 69% of patients with AIDS were positive for HIV-Ag as were 46% of patients with ARC and 19% of asymptomatic, HIV-antibody-positive individuals. There were significant associations between the stage of HIV infection--ie, AIDS vs ARC vs asymptomatic--and the detection of HIV-Ag in serum (p less than 0.0001) and the lack of detection of antibody to HIV core Ag (p less than 0.0001). HIV-Ag was also found in the serum of two asymptomatic antibody-negative individuals who were at high risk for AIDS and who later developed HIV antibody. The presence of HIV-Ag in sera was confirmed by an inhibition procedure. Thus, HIV-Ag can be detected in the serum of infected individuals prior to antibody production and correlates with the clinical stage of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunoglobulin G class and subclass antibodies to pneumococcal capsular polysaccharides.

Enzyme immunoassays were developed to measure immunoglobulin G (IgG) and IgG1-4 subclass antibodies to pneumococcal capsular polysaccharides (PCP) types 4 and 7F. In healthy subjects, anti-PCP antibodies were predominately of the IgG1 and IgG2 subclasses. There was a significant increase in IgG, IgG1, and IgG2 anti-PCP antibody concentrations following immunization with pneumococcal vaccine. IgG and IgG2, but not IgG1, anti-PCP antibody concentrations correlated with total anti-PCP antibody concentrations measured by the standard radioimmunoassay and with serum opsonic activity for serotype 7F Streptococcus pneumoniae. Such IgG and IgG subclass antigen-specific antibody assays may be useful to investigate the immune response to pneumococcal polysaccharides.

Adult↗
PubMed1987

Tamarin model of pneumococcal bacteremia.

Tamarins (Saguinus labiatus) were utilized to study host defenses against pneumococcal bacteremia. Tamarins had a poor antibody response to immunization with varying doses of pneumococcal capsular polysaccharide (PCP) vaccine (2 of 15 positive) or to infection with serotype 7F Streptococcus pneumoniae (2 of 14 positive). Tamarins were protected against challenge with a lethal dose of serotype 7F S. pneumoniae if the bacteria were preopsonized with human immune globulin intravenous or if the tamarins were injected with the immune globulin 30 min before challenge. There was minimal protection utilizing a mouse monoclonal anti-type 7F PCP antibody.

Animals↗
PubMed1986

Sensitivity to non-acetylated salicylates in a patient with asthma, nasal polyps, and rheumatoid arthritis.

A woman experienced exacerbations of bronchial asthma after taking aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis. On oral challenges, she developed an urticarial reaction after tartrazine; urticarial and bronchospastic reactions after salicylsalicylic acid; and urticarial and bronchospastic reactions after choline magnesium trisalicylate. Non-acetylated salicylates have been recommended for use in aspirin- and/or tartrazine-sensitive patients. The results of sensitivity studies of our patient indicates that such patients may also be sensitive to non-acetylated salicylates.

Albuterol↗
PubMed1985

Maternal-fetal transfer of pneumococcal capsular polysaccharide antibodies.

Maternal-fetal transfer of IgG antibodies is an important host defense for newborns, who have an increased incidence of bacterial infections. To study the transfer of specific pneumococcal capsular polysaccharide (PPS) antibodies, we measured the concentrations, in 30 paired maternal and cord serum samples, of IgG and IgM by radial immunodiffusion, of serotype 7F Streptococcus pneumoniae PPS antibodies by radioimmunoassay and enzyme immunoassay, and of opsonic activity to that organism by a radiolabeled bacterial uptake assay. Cord serum had significantly greater total IgG, yet significantly less type 7F PPS IgG antibodies and opsonic activity than maternal serum. Cord serum had low concentrations of total IgM and no IgM type 7F-specific antibodies. Reduced transport of specific IgG antibodies and absent transfer of IgM may contribute to the susceptibility of newborns to bacterial infection.

Antibodies, Bacterial↗
PubMed1985

Increased activation of the alternative complement pathway in sickle cell disease.

Complement proteins play an important role in host defenses against Streptococcus pneumoniae, a major cause of serious infections in sickle cell (SS) disease. Previous studies have suggested abnormalities of the alternative complement pathway in SS disease. We measured activation of the alternative pathway in sera from patients with SS disease utilizing an enzyme immunoassay which detects C3b,P complexes, derivative of the C3b,Bb,P alternative pathway convertase. In all, 89% of SS sera had elevated concentrations of C3b,P complexes, indicative of increased alternative pathway activation. Chronic activation of the alternative pathway may contribute to impaired host defense in SS patients.

Anemia, Sickle Cell↗
PubMed1985

Correlation of serum opsonins with in vitro phagocytosis of Streptococcus pneumoniae.

C-reactive protein (CRP), an acute-phase reactant which binds to phosphocholine (PC) in the pneumococcal cell wall, and anti-PC antibodies are protective against experimental pneumococcal bacteremia in mice. To determine the relative opsonic capacities of CRP and anti-PC compared with those of antibodies against pneumococcal capsular polysaccharides (anti-PCP), we correlated in vitro opsonic activity for serotype 7F Streptococcus pneumoniae with concentrations of CRP, anti-PC, and anti-type 7F PCP in human sera from 10 normal subjects and 38 patients with sickle cell (SS) disease, a high-risk group for pneumococcal infection. Opsonic activity, measured by a radiolabeled bacterial uptake assay, correlated with anti-PCP levels but not with CRP or anti-PC in both the normal subjects and patients with SS disease. Addition of CRP to normal sera did not increase opsonic activity for serotypes 4 and 7F S. pneumoniae, although it did so for serotype 27, a nonpathogenic strain unique for having PC in its capsule. CRP and anti-PC were not effective opsonins when they bound to the pneumococcal cell wall rather than the capsule. The protective effects of CRP or anti-PC against these serotypes may be produced by means other than complement-dependent opsonization.

Adult↗
PubMed1983

Significance of a positive antinuclear antibody test in a pediatric population.

Clinical and laboratory findings in 138 children seen during a ten-year period with a positive antinuclear antibody (ANA) test were reviewed. Two thirds (91 of 138) of the patients had specific autoimmune or rheumatic diseases, including systemic lupus erythematosus (n = 37), juvenile rheumatoid arthritis (n = 33), Sjögren's syndrome (n = 9), mixed connective tissue disease (n = 7), dermatomyositis (n = 3), and discoid lupus (n = 2). Another 27 patients had symptoms of autoimmune disease but did not fit criteria for specific disorders. Nine patients with IgA deficiency had a positive ANA test but did not have symptomatic autoimmune disease. Ten children had a positive ANA test in association with infections, mainly viral, and one had leukemia. Because most children with a positive ANA test had readily diagnosable autoimmune disorders, pediatric patients with a positive ANA on repeated testing should undergo clinical and laboratory studies for autoimmune or rheumatic disease.

Adolescent↗
PubMed1983

Patients with abnormal proportions of T-lymphocyte subsets have reduced in vitro cellular immunity.

Monoclonal antibodies which identify helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of human T lymphocytes have recently been used to investigate immunoregulation in isolated cell populations, as well as in human disease states. However, the relationship between relative proportions of OKT4- and OKT8-positive blood lymphocytes and in vitro cellular immune function in patients with immunodeficiencies has not been studied extensively. We enumerated T-lymphocyte subsets with OKT4 and OKT8 antibodies, and measured proliferative responses to allogeneic cells in mixed lymphocyte culture (MLC) and to phytohemagglutinin (PHA), in peripheral blood mononuclear cells (PBMCs) from 60 patients with varying degrees of immunodeficiency and 20 healthy controls. Controls had 56.0 +/- 5.3% (mean +/- 1SD) OKT4-positive lymphocytes, 28.6 +/- 5.9% OKT8-positive lymphocytes, and an OKT4/8 ratio of 2.05 +/- 0.55. We defined as abnormal values of less than 40% OKT4-positive or greater than 45% OKT8-positive lymphocytes (3 SD below and above mean values, respectively), or an OKT4/8 ratio of less than 1.2. Patients with these abnormal percentages of T-lymphocyte subsets had significantly lower mean MLC and PHA responses (P less than 0.001), and higher incidences of abnormal MLC and PHA responses (P less than 0.01). Abnormal proportions of T-lymphocyte subsets correlated with low MLC and PHA responses in most immunodeficient patients, although some patients with low MLC and PHA responses had normal subset distributions. T-Cell subset proportions were heterogeneous among patients with the same diagnosis.

Adult↗
PubMed1983

Clinical and laboratory findings in childhood mixed connective tissue disease: presence of antibody to ribonucleoprotein containing the small nuclear ribonucleic acid U1.

Seven children and adolescents are described with mixed connective tissue disease. The patients had varying clinical features, commonly characterized by Raynaud phenomenon, arthritis, abnormal pulmonary function, and esophageal dysmotility. All patients had speckled antinuclear antibodies and high titers (greater than 1:100,000) of antibodies to ribonuclease-sensitive extractable nuclear antigen. We prepared extractable nuclear material from radioactively labeled HeLa cells, analogous to classic extractable nuclear antigen. Sera from all seven patients precipitated ribonucleoprotein containing the small nuclear ribonucleic acid species U1 from the HeLa cell extract. Antibody to U1 ribonucleoprotein was not found in sera from 51 of 53 children and adults having a variety of autoimmune and other diseases, nor in sera from nine normal individuals. The U1 ribonucleoprotein appears to be the component of extractable nuclear antigen characteristically reacting with sera from patients with mixed connective tissue disease. The finding of a distinct molecular marker in all children studied with mixed connective tissue disease indicates that this is a distinct disease entity and not a heterogeneous population of immune disorders.

Adolescent↗
PubMed1983

Increased serum opsonic activity and antibody concentration in patients with sickle cell disease after pneumococcal polysaccharide immunization.

Opsonic defects have been reported in unimmunized patients with sickle cell disease. We found significant increases (P less than 0.001) in serum opsonic activity, measured by a radiolabeled bacterial uptake assay, and in type 7 pneumococcal polysaccharide antibody concentration in 17 such patients 2 years of age or older after pneumococcal polysaccharide immunization. All 17 patients and six healthy controls achieved a type 7 antibody concentration of more than 300 ng antibody nitrogen per milliliter, believed to be the protective level of antibody in vivo. Six patients with sickle cell disease less than 2 years of age did not have a significant increase in type 7 antibody concentration after immunization. Only three of these six patients achieved a postimmunization type 7 antibody concentration exceeding 300 ng Ab N/ml. Overall, 16 of 23 patients with sickle cell disease (70%) had a twofold or greater increase in type 7 antibody concentration, and 13 of these (81%) had a corresponding increase in opsonic activity (P less than 0.001). Thus most patients who responded to pneumococcal polysaccharide immunization had a concurrent increase in opsonic activity in vitro.

Adolescent↗