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Biomedical subjects

R D Rossen

Publications and source records attributed to R D Rossen.

At least 73 records · Page 4Linked to original sources
PubMed1979

The effect of age on the character of immune complex disease: a comparison of the incidence and relative size of materials reactive with Clq in sera of patients with glomerulonephritis and cancer.

The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S.

Adolescent↗
PubMed1979

Role of immune complexes in rheumatoid polyarteritis.

Serial clinical and serological observations were made on a patient with necrotising polyarteritis associated with rheumatoid arthritis. Significant levels of circulating immune complexes, as determined by a C1q binding assay, were observed up to 2 years before the clinical manifestations of polyarteritis but rose abrumptly immediately before and concurrently with the onset of polyarteritis. Concomitant serial determinations of C3, latex fixation titres for anti-immunoglobulin, and patterns of fluorescence of antinuclear antibody afforded insight into the nature of these somplexes, as did clinical and serological response to glucocorticoid and cytotoxic therapy. Our data suggest that the antibody involved in the complex was of the IgG class and capable of complement fixation.

Antibodies, Anti-Idiotypic↗
PubMed1978

Rheumatoid factor positive plasma and humoral cytotoxicity to malignant melanoma.

Complement dependent cytotoxicity to malignant melanoma tumor cells was demonstrated in incubations that included rheumatoid factor (RF) positive plasma and normal plasma. Cytotoxicity was not demonstrated to cells from a number of normal tissues. The phenomenon involved coating of tumor cells with immunoglobulins and complement fixation. The activity in RF positive plasma was present in high titer an may not be RF. The activity in normal plasma was present in low titer, was found in plasma from eight out of 11 healthy subjects and may be a naturally occurring antibody. This previously undescribed humoral cytotoxicity system may participate in tumor host interactions, especially after therapy, when the majority of patients become RF seropositive.

Animals↗
PubMed1978

Detection of immune complex-like materials in cancer patients' sera: a comparative study of results obtained with the C1q deviation and C1q binding tests.

In a collaborative study involving three laboratories, randomly coded sera from 47 patients and healthy donors were tested for soluble immune complexes by two versions of the C1q BT and by the C1q DT. Analysis of ranked data showed a close correlation between results obtained in all laboratories as well as good reproducibility on testing coded duplicate samples included in each panel of sera. However, with the use of values for normal donors established independently in each laboratory, the tests did not always agree in discriminating normal from abnormal sera, particularly with sera from cancer patients. Results reflected to some extent the methods used to inactivate the endogenous C1 complex in the test sera. Studies of 130 additional cancer patients revealed that 44 (34%) gave abnormal C1q BT values when inactivated with EDTA but only 35 (27%) were abnormal when heat inactivated (56 degrees for 30 min). Similarly 12 of 65 sera (18%) from patients with nonneoplastic diseases and 10 of 80 (13%) from healthy donors gave significantly abnormal results after addition of EDTA. Eight (12%) of the disease and six (8%) of the healthy controls' sera were similarly outside normal limits when heat inactivated. Repeated freezing and thawing of sera or changes in the concentration of PEG used to precipitate complex-bound 125I-C1q influenced C1q BT results more than duration of storage at -70 degrees C or changes ascribed to presence or absence of rheumatoid factors and CRP.

Antigen-Antibody Complex↗
PubMed1978

Response of malignant melanoma to plasma exchange, surgical debulking, and Corynebacterium parvum.

A 48 year old man with extensive cutaneous and subcutaneous metastatic malignant melanoma responded to treatment by repeated plasma exchanges, partial surgical debulking of tumor masses, and intravenous Corynebacterium parvum. Circulating immune complexes were measured by the serum C1q binding method. Tumor regression coincided with serum C1q binding reduction to normal levels. Clinical relapse was preceeded by recurrent elevation of serum C1q binding activity.

Binding Sites↗
PubMed1977

Penicillin-induced immunohemolytic anemia associated with circulating immune complexes.

Eleven days after administration of multiple penicillin analogs, a 55-year-old female developed a Coombs-positive hemolytic anemia. The patient's erythrocytes were coated with IgG, complement components (C4/C3) and her serum contained elevated 125I-Clq binding activity (a measure of the presence of immune complexes). Her serum, in the presence of fresh complement and penicillin, induced complement sensitization of normal erythrocytes. Immune complex-mediated complement activation and the haptene type of erythrocyte sensitization accounted for accelerated red blood cell destruction in this patient.

ABO Blood-Group System↗
PubMed1977

Renal localization of antiglobulins in glomerulonephritis and after renal transplantation.

Localization of fluorescein-conjugated heat-aggregated IgG (FA IgG) was demonstrated by immunofluorescence in renal glomeruli of 16 of 69 patients with glomerulonephritis. FA IgG bound more frequently in kidney biopsies from patients with diffuse glomerulonephritis and depressed renal function, and localized selectively in glomeruli that contained heavy deposits of IgM, C3, and C4. The factors that caused FA IgG to bind were specifically reactive with the Fc piece of the IgG molecule and were resistant to 56 degrees C heat for 30 minutes. Localization of FA IgG in the kidney did not correlate with the presence of soluble immune complexes or detectable antiglobulin antibodies in the sera. Binding of FA IgG was also seen in glomeruli and arteries of 18 of 21 kidney allografts studied at the time of impending rejection. But the factors responsible for binding FA IgG in the allografts were heat labile and thus could have been C1q. Although the role of these "antiglobulins" in the immunobiology of glomerulonephritis remains unknown, the fact that they occurred mainly in patients with relatively severe glomerular injury suggests that they could play some part in promoting renal glomerular injury.

Adolescent↗
PubMed1977

Effect of plasma exchange on circulating immune complexes and antibody formation in patients treated with cyclophosphamide and prednisone.

A patient with systemic lupus erythematosus (SLE) and a patient with an immune complex disease resembling Goodpasture's syndrome were treated with cyclophosphamide, prednisone and repeated plasma exchanges. Circulating immune complexes decreased, and symptoms of central nervous system disease remitted for up to 15 to 20 days after plasma exchange in the patient with SLE. In vitro lymphocyte blastogenic responses to antigens were also transiently increased on two occasions following treatment. In the second patient, decreases in circulating immune complexes and clinical improvement were ascribed chiefly to immunosuppressive drug treatment. Serum antibody to keyhole limpet hemocyanin was relatively unaffected by plasma exchange in both patients. These results suggest that plasma exchange may help to deplete circulating immune complexes or alter the equilibrium between soluble antigen and antibody which causes complexes to form and circulate. It may be less effective in reducing circulating antibody levels in patients who continue to produce new antibody.

Adult↗
PubMed1977

The C1q binding test for soluble immune complexes: clinical correlations obtained in patients with cancer.

Sera from 134 selected patients with various types of cancer were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in cancer patients' sera and treatment with DNase did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4 cancer patients showed that the major binding activity was found between 19S and 7S.

Antibodies, Anti-Idiotypic↗
PubMed1977

Normal human bronchial immunoglobulins and proteins: effects of cigarette smoking.

Selected proteins were compared in bronchial lavage fluids recovered from 36 healthy nonsmokers and 19 healthy cigarette smokers. Although fluids lavaged from smokers contained 4 times as many cells (more than 80 per cent macrophages) as fluids from nonsmokers, there were no quantitative differences between the two groups in immunoglobulin A, a1-antitrypsin, a2-globulin, transferrin, or albumin content. However, immunoglobulin G content of bronchial fluids from smokers was twice as high as that from nonsmokers. This selective increase in immunoglobulin is compatible either with stimulated local bronchial immunoglobulin production or the selective exudation of plasma immunoglobulin into alveolar spaces in response to inhaled cigarette smoke.

Adult↗
PubMed1977

Intravascular hemolysis, thrombocytopenia, leukopenia, and circulating immune complexes after jejunal-ileal bypass surgery.

Two years after jejunal-ileal bypass surgery for obesity, a 25-year-old man developed intravascular hemolysis, thrombocytopenia, and neutropenia. The patient's erythrocytes were coated with complement components (C4/C3) and his serum induced complement-dependent immune lysis of chromium-51-labeled platelets. Serum [125I]-C1q binding activity (a measure of the presence of immune complexes) was increased, and serum C4 and C3 hemolytic titers were depressed. Immune complex-mediated complement activation apparently accounted for the blood cell destruction in this patient.

Adult↗
PubMed1976

Specific in vitro binding of radiolabeled antibodies to cell surface antigens: interaction of antihuman thymocyte globulin with human target cells.

We have developed a highly sensitive and reproducible in vitro method to measure the rate and amount of binding of radiolabeled antibodies to target cells. We reduced non-specific binding of the antibodies to the target cells approx. 92% by removing protein aggregates from the antibody solutions. Using a specially designed cup that simultaneously allows washing and collection of target cells, cell loss was eliminated. This method was used to study the in vitro binding properties of the IgG fraction of anti-human thymocyte globulin (ATG) to nucleated human cells and to cells of other species. We found the initial rapid uptake of labeled ATG-IgG slowed with prolonged incubation. Incubation temperature and ATG concentration increased the rate of uptake. Sequential absorption studies indicated that initial uptake was due to rapidly binding antibodies. After these antibodies were removed, the rate of binding for antibodies that remained was several fold less than that of the antibodies removed by the initial absorption. Since temperature and the concentration of antibody and target cells can be rigidly controlled, this in vitro model system is ideally suited to quantify optimal conditions and kinetics of antibody binding to cell membrane antigens. Furthermore, the binding properties of antibody subpopulations in an antiserum may be determined by this technique. The maximum antibody binding capacity of various cell types can also be measured using the technique with a precision of +/- 14% on replicate determinations.

Animals↗
PubMed1976

Soluble immune complexes in sera of patients with nephritis.

Binding of radioactively labeled C1q was used to detect soluble antigen-antibody complexes in sera collected at the time of renal biopsy from 104 patients with immunofluorescent findings consistent with immune-complex disease. In comparison with data obtained with sera from 85 healthy donors, significantly elevated C1q binding activity was demonstrated in sera from 22 patients. C1q binding was elevated in all four patients whose dominant histologic finding on bright field microscopy was an intense interstitial mononuclear cell infiltrate. High C1q binding activity was found preferentially in sera from patients who had diffuse rather than focal histologic abnormalities by light microscopy, heavy glomerular deposits of C4 and C3 by immunofluorescence and elevated serum creatinine concentrations. However, there were many patients with similar immunofluorescent and bright field microscopic changes in whom circulating complexes were not detected and there was no correlation between the pattern of glomerular localization of immune complexes and the C1q binding activity of the sera. Serial measurements of C1q binding activity in the sera from three patients over a 90-day interval emphasized that immune complexes may be demonstrated by this technique only intermittently in the sera of some patients with renal biopsy evidence of immune-complex disease. Nevertheless, these observations suggest that the C1q binding test may be a useful tool to monitor disease activity in patients with immunologically mediated renal disease.

Adult↗