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Biomedical subjects

D Koffler

Publications and source records attributed to D Koffler.

At least 37 records · Page 2Linked to original sources
PubMed1979

Association of IgG anti-brain antibodies with central nervous system dysfunction in systemic lupus erythematosus.

Sera from 20 patients with systemic lupus erythematosus (SLE) and active central nervous system (CNS) dysfunction were examined by indirect immunofluorescence for antibodies to neuronal membrane determinants. Warm-reactive IgG antibodies were demonstrable in 82% (9/11) of patients with clinical evidence for seizures or diffuse CNS disease, but these antibodies generally were absent in non-CNS SLE sera or when focal neurologic deficit or psychosis was the primary CNS manifestation. Cold-reactive antibodies of the IgM class were equally prevalent in patients with or without CNS disease and appeared to be more directly correlated with extra-CNS systemic illness. Absorption experiments with lymphocytes, brain homogenate, and various other tissues suggested a predominant brain-specificity for IgG antibodies and partial lymphocyte cross-reactivity for IgM antibodies. Interpretations of this special association between IgG anti-brain antibodies and diffuse CNS dysfunction in SLE are discussed.

Autoantibodies↗
PubMed1979

Studies on the specificity and clinical correlation of antiribosomal antibodies in systemic lupus erythematosus sera.

The specificity of antibodies reactive with cytoplasmic ribosomes detected in systemic lupus erythematosus (SLE) sera was studied by a radioimmunoassay procedure with 3H labeled HeLa cell polysomes. The antibodies were directed primarily against RNA or a ribosomal RNA-protein complex (rRNP). Anti-RNA antibodies exhibited comparable reactivity with ribosomal RNA, nuclear RNA, structural RNA, and a slightly lower degree of reactivity with low molecular weight RNA. Anti-rRNP antibodies may be detected by precipitation in agar gel and appear to require both the RNA and protein moieties of ribosomes for reactivity. SLE sera containing only anti-rRNP antibodies are limited to patients with active disease. Sera from patients with both active and inactive SLE contain either anti-RNA or a mixture of anti-RNA and anti-rRNP antibodies. The possible participation of anti-ribosomal antibodies in immune complex formation is discussed.

Antibodies, Antinuclear↗
PubMed1978

Serologic studies in patients with systemic lupus erythematosus and central nervous system dysfunction.

Serologic studies were performed on 25 patients with systemic lupus erythematosus (SLE) during 29 acute episodes of central nervous system (CNS) disease. Increased anti-DNA antibody and decreased total serum hemolytic complement activity were observed only in those patients with associated extra-CNS disease manifestations. Patients with isolated CNS disease were otherwise in apparent clinical and serological remission regarding these two indices. No special association of cold-reactive IgM antilymphocyte antibodies was demonstrable in patients with ongoing CNS injury. Of special interest was an increased incidence of anti-Sm antibodies in the patients with CNS dysfunction relative to that in a large group of patients without neuropsychiatric disease. The incidence of anti-RNP was not increased. The data do not support direct involvement in SLE brain injury of either DNA/anti-DNA complexes or of lymphocytotoxic antibodies cross-reactive with brain cells, but do suggest an association of anti-Sm with CNS disease in this disorder.

Antibodies↗
PubMed1977

Radioimmunoassay for antibodies to cytoplasmic ribosomes in human serum.

A radioimmunoassay for the detection of antibodies in human serum to tritium-labeled HeLa cell cytoplasmic ribosomes was developed with the use of Macaloid for the inhibition of endogenous ribonuclease activity. Antibodies were observed in the serum of patients with systemic lupus erythematosus in high incidence and titer. Patients with rheumatoid arthritis and chronic active hepatitis manifested a lower incidence and titer of antibodies to ribosomes, whereas serums from normal individuals and from patients with sarcoidosis, chronic glomerulonephritis, and malignant tumors showed no significant reactivity with cytoplasmic ribosomes. Maximum inhibition of the reaction was achieved with unlabeled HeLa cell ribosomes or rat liver ribosomes and partial inhibition by purified ribosomal RNA.

Animals↗
PubMed1977

Leukocyte migration in ovarian carcinoma: comparison of inhibitory activity of tumor extracts.

Inhibition of migration of leukocytes from patients with serous cystadenocarcinoma of the ovary was studied by the use of several different types of ovarian carcinoma extract as antigen. KCl extract of an ovarian carconoma was found to be the most effective antigen preparation in comparison with saline, deoxycholate, and perchloric acid extracts. Low concentrations of KCl ovarian carcinoma extract significantly inhibited migration of leukocytes from 11 of 17 patients with ovarian carcinoma (migration index, less than 0.74). Leukocytes from patients with breast, colon, or endometrial carcinoma showed minimal reactivity with ovarian carcinoma KCl extract, and leukocytes from patients with ovarian carcinoma showed minimal reactivity with KCl extracts of breast, colon, and endometrial carcinoma. These results suggested that the 3 M KCl procedure is superior for the isolation of antigens active in the leukocyte migration inhibition test and that this test may be of use for the isolation of tumor-associated antigen and the immunodiagnosis of ovarian carcinoma.

Antibody Specificity↗
PubMed1977

Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.

Significant differences in both specificity and avidity of anti-DNA antibodies were observed in the sera of groups of patients with active systemic lupus erythematosus glomerulonephritis, active systemic lupus erythematosus without nephritis, and in IgG eluates obtained by DNAase digestion of isolated glomeruli from glomerulonephritic kidneys. With methylated albumin-kieselguhr fractionated 3H-HeLa DNA as a source of native or single-strand DNA antigen in a modified Farr assay, an increased level of antibody to native DNA was associated with active systemic lupus erythematosus, particularly active nephritis. The avidity of antinative DNA estimated from plots of the reciprocals of bound and free antigen according to the Sips distribution formula was significanly lower in active glomerulonephritis sera than in sera from patients with active systemic lupus erythematosus without nephritis. However, antinative DNA of uniformly high avidity was found in the glomerular eluates. Avidity of single-strand DNA antibodies did not differ in the various patient groups. The data stronly supprot a major role for high avidity antinative-DNA in DNA/antiDNA immune complex-induced glomerular injury in systemic lupus erythematosus.

Antibodies, Anti-Idiotypic↗
PubMed1976

Cellular hypersensitivity in patients with adenomatous hyperplasia and adenocarcinoma of the endometrium.

Cellular hypersensitivity was studied in patients with adenomatous hyperplasia and adenocarcinoma of the endometrium with the use of dinitrochlorobenzene (DNCB) skin tests and inhibition of leukocyte migration by homologous and autologous tumor antigen. Inhibition of leukocyte migration by homologous endometrial carcinoma antigen was found in two of five patients with adenomatous hyperplasia and eight of 11 patients with endometrial adenocarcinoma. A comparable degree of inhibition was found with autologous antigen. DNCB skin reactions were found to be strongly positive in patients with adenomatous hyperplasia, and a lesser degree of reactivity was observed in patients with endometrial adenocarcinoma. No correlation was found between leukocyte migration tests and DNCB reactions, and no correlation was observed between these tests and the age of the patient, clinical stage of disease, or histologic grade of the tumor.

Adenocarcinoma↗
PubMed1975

Cellular hypersensitivity in patients with squamous cell carcinoma of the cervix.

A group of patients with squamous cell carcinoma of the cervix were tested for cellular hypersensitivity prior to the initiation of therapy. Fourteen of 15 patients manifested inhibition of leukocyte migration with homologous tumor extracts, and 13 patients showed inhibition with autologous tumor extracts. Lymphocytes from 10 to 11 patients exhibited cytotoxicity for a homologous cell line and lymphocytes from 4 to 5 patients, for autologous cell lines. These results indicate that the absence of cellular hypersensitivity is infrequent in patients with squamous cell carcinoma. A comparison of the degree of sensitivity detected by use of each test showed a good correlation in a group of 10 patients. The efficacy of both autologous and homologus antigens to react with sensitized leukocytes supports the hypothesis that these antigens are tumor related. Although no correlation was found among the immunologic tests, clinical status of the patient, or prognosis based on the evaluation of several histologic parameters, further studies are needed to determine the usefulness of these tests as a prognostic index in individual patients, especially in patients with Stage I carcinoma.

Adenocarcinoma↗
PubMed1975

Specific concentration of polynucleotide immune complexes in the cryoprecipitates of patients with systemic lupus erythematosus.

Although the association of cryoglobulinemia with hypocomplementemia and tissue injury in systemic lupus erythematosus is well recognized, composition of cryoprecipitates in terms of circulating antigens and antibodies in this disease is less clear. To clarify this question, cryoprecipitates from patients with SLE were examined with sensitive assay techniques for certain antipolynucleotide antibodies and DNA antigen. DNA antibodies were highly enriched relative to serum levels in the majority of cryoprecipitates. DNA antigen was also demonstrable. Antibody to ribonucleoprotein, although less frequently present, was similarly enriched in certain cryoprecipitates. In contrast, anti-double strand RNA, which was commonly detectable in relatively high titer in serum, was only minimally concentrated in a minority of cryoprecipitates. Absorption experiments using red blood cells heavily coated with polynucleotide antigen indicated that a major proportion of the IgG in certain cryoprecipitates was specific antibody. The data strongly suggest that the cryoprecipitates in systemic lupus erythematosus represent circulating immune complexes that are soluble at 37 degrees C and come out of solution in the cold. The marked concentration of immune complexes in the cryoglobulin offers a simple and direct method for determination of the nature of the complexes. The accumulated evidence obtained in the present study indicates that these complexes closely reflect, in their composition, the circulating immune complexes which are most significant pathogenetically in renal tissue injury.

Antibodies, Antinuclear↗
PubMed1975

Mechanisms of tissue injury in systemic lupus erythematosus.

SLE is a syndrome with protean clinical manifestation, a diversity of immunologic abnormalities, and a host of potential etiologic agents. In recent years, considerable information has been accumulated concerning the immunopathogenesis of SLE, and significant advances have been made in the treatment of the disease by utilizing immunosuppressive therapy. Further investigation will be needed to clarify the mechanisms of tissue injury, especially as they relate to the CNS, and to identify the factors responsible for initiating the SLE syndrome.

Antigen-Antibody Complex↗
PubMed1974

Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus.

Several types of antipolynucleotide antibodies were eluted by acid buffer or deoxyribonuclease treatment of glomeruli obtained from nine kidneys from patients with systemic lupus erythematosus (SLE). Anti-SDNA antibodies were found concentrated over serum levels in eight eluates, anti-NDNA in six eluates and anti-RNA Pr in four eluates; anti-DSRNA antibodies were not demonstrable in any eluate tested. Deoxyribonuclease treatment eluted a high incidence and greater quantity of anti-NDNA and anti-SDNA antibody, whereas anti-RNA Pr antibody was mainly eluted by acid buffer. Simultaneous studies of antibody and antigen in serial serum specimens and in glomeruli suggested that complexes of SDNA antibody or antigen excess were frequently deposited in SLE kidneys, in addition to complexes containing anti-NDNA and anti-RNA Pr. It was observed that studies of antibody titers alone were inadequate for predicting the types of complexes deposited in the kidney. Either antigen excess could obscure detection of humoral antibody or extremely high titers of antibody as observed for RNA Pr are not conducive to the formation of kidney localizing immune complexes in the absence of antigen. Immunofluorescence studies demonstrated the presence of SDNA antigen in most cases from which anti-SDNA antibody was eluted providing direct evidence for the presence of SDNA-anti-SDNA complexes in renal glomeruli. A study of complement components indicated that Clq was absent from cases in which little or no SDNA was deposited in renal glomeruli; although all nephritic kidneys demonstrated C3 deposits. Several hypotheses accounting for this observation are discussed, including the probable utilization of the alternate pathway by certain types of complexes and a direct reaction between C1q and circulating or tissue-bound NDNA or SDNA.

Animals↗