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Biomedical subjects

F H Gmelig Meyling

Publications and source records attributed to F H Gmelig Meyling.

At least 19 recordsLinked to original sources
PubMed1994

Soluble CD8 and CD25 in serum of patients after heart transplantation.

To evaluate the diagnostic value of serum cytokine levels and cytokine receptor levels in the diagnosis of acute rejection after heart transplantation, we measured soluble CD8 and soluble CD25 in the serum of heart transplant recipients. The results were compared with endomyocardial biopsy (EMB) histopathology, lymphocyte activation by morphologic inspection of peripheral blood cells (cytoimmunologic monitoring), clinically manifested infections, and the maintenance immunosuppressive therapy. Significantly increased levels were observed in cases of lymphocyte activation in cytoimmunologic monitoring indicative of either rejection or infection. In clinically documented cytomegalovirus (CMV), bacterial, and Pneumocystis carinii infections, increased levels of soluble CD25 were observed. Soluble CD8 was only increased in a single case of P. carinii infection. A statistically significant correlation was calculated between the levels of soluble CD8 and whole blood cyclosporin A level. Considering chemotherapy, the levels of soluble CD8 showed an inverse correlation with the daily dosage of azathioprine. In conclusion, the levels of soluble CD8 and CD25 are associated with lymphocyte activation in peripheral blood, but do not differentiate between lymphocyte activation indicative of rejection or infection. No relationship was observed between levels of soluble CD8 and CD25, and EMB histopathology. Therefore, the assessment of these two cell products has no diagnostic potential for monitoring acute rejection after heart transplantation.

CD8 Antigens↗
PubMed1993

Endomyocardial biopsies after heart transplantation. The presence of markers indicative of activation.

A series of 104 endomyocardial biopsies (EMB) from patients after heart transplantation was evaluated for the presence of immunological markers on graft component and infiltrating cells. This included markers for cells expressing alpha beta-T-cell receptors and gamma delta-T-cell receptors, and cytotoxic T cells with granules bearing the serine esterase Granzyme B; the presence of activation markers identified by CD25 (interleukin 2 receptor), CD30, CD69 (activation inducer molecule), CDw70; macrophages using antibody CD14 (WT14), and cells with Fc gamma-receptors type III (CD16). Almost all cells in T-cell infiltrates expressed the alpha beta-T cell receptor. Cells bearing the gamma delta-T cell receptor were scarcely found. The analysis with respect to the histopathologic diagnosis for rejection showed an absence of significance for T cell subsets, Granzyme B-positive cells, and activation markers except CD25. The numbers of macrophages labeled by CD14 and cells expressing Fc gamma RIII showed a significant relation to histopathology of rejection. Apart from leukocytes, also endothelium in EMB with rejection was labeled by the two anti-Fc gamma RIII antibodies used. In addition, in a small series of biopsies investigated, Fc gamma RI- and Fc gamma RII-positive cells were increased in EMB with rejection, and endothelium was labeled by Fc gamma RII antibodies. A cluster analysis on the basis of scores for CD25, CD14, and anti-Fc gamma RIII revealed three main clusters, one cluster comprising biopsies without abnormalities, one cluster containing EMB with the histopathology of rejection and high scores in immunophenotyping for lymphocytes and macrophages, and one cluster in between. The present data emphasize the importance of macrophage assessment in evaluating pathologic processes during rejection of heart allografts and diagnosing rejection.

Antibodies↗
PubMed1991

Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus.

The processes that govern the generation of pathogenic anti-DNA autoantibodies in human systemic lupus erythematosus (SLE) are largely unknown. Autoantibodies may arise as a consequence of polyclonal B cell activation and/or antigen-driven B cell activation and selection. The role of these processes in humoral autoimmunity may be studied by molecular genetic analysis of immunoglobulin (Ig) variable (V) regions of antibodies that are characteristic of SLE. We have analyzed the gene elements that encode a high affinity, IgG anti-double-stranded DNA autoantibody secreted by a monoclonal Epstein-Barr virus (EBV)-transformed cell line derived from a patient with active SLE. In addition, we have identified, cloned, and sequenced the germline counterparts of the VH and VL genes expressed in this autoantibody. The comparison of both sets of gene elements shows that the autoantibody VH and VL regions harbor numerous somatic mutations characteristic of an antigen-driven immune response. The light chain expressed in this autoantibody is a somatically mutated variant of the kv325 germline gene that is frequently associated with paraproteins having autoantibody activity and with Ig molecules produced by malignant B cells that express the CD5 antigen. Furthermore, the utilized DH segment has been repeatedly found in multireactive, low affinity IgM anti-DNA autoantibodies from SLE patients and healthy individuals. These results suggest that pathogenic IgG anti-DNA autoantibodies in human SLE may arise through antigen-driven selection of somatic mutations in the gene elements that frequently encode multireactive IgM autoantibodies.

Amino Acid Sequence↗
PubMed1990

A prospective study on antiribosomal P proteins in two cases of familial lupus and recurrent psychosis.

In two siblings with systemic lupus erythematosus (SLE), who experienced two episodes of psychosis each, a longitudinal study of autoantibodies, including antibodies to ribosomal P proteins, is described. In two of three evaluable periods of 15 weeks antedating psychosis a rise followed by a spontaneous drop in anti-P levels was recorded. In the third period antibodies to ribosomal protein P were absent. It is concluded that results with single samples are not informative, and that frequent measurement of antibodies to ribosomal protein P in patients with SLE may have limited predictive value for psychosis.

Adult↗
PubMed1990

Monitoring rejection after heart transplantation: cytoimmunological monitoring on blood cells and quantitative birefringence measurements on endomyocardial biopsy specimens.

Cytoimmunological monitoring and quantitative birefringence measurements were used as potential aids in diagnosing acute rejection after heart transplantation instead of histopathological assessment of the endomyocardial biopsy specimen alone. Cytoimmunological monitoring was based on morphological inspection and quantitation of mononuclear cells, particularly activated lymphoid cells. Quantitative birefringence measurements comprise a variable for myocyte contractile function. Its read out is the ratio of the degree of birefringence before contraction to that after. Cytoimmunological monitoring indicated significantly higher concentrations of activated lymphocytes in moderate or severe acute rejection, and quantitative birefringence measurements indicated decreased myocyte function during severe and resolved or resolving rejection. Cytoimmunological monitoring and quantitative birefringence measurements were diagnostically most useful in terms of sensitivity, specificity, and predictive value, when only data gathered before the first episode of acute rejection were considered. For cytoimmunological monitoring, diagnostic relevance was optimal when the data were expressed as relative proportions of activated lymphocytes. The quantitative birefringence measurements correlated best with analysis of the endomyocardial biopsy specimen when a cut off value of 1.25 was used. When both methods for diagnosing acute rejection were analysed together, no improvement in sensitivity (value 0.44) was found, but the specificity increased to 0.98 and the predictive value to about 0.80. It is concluded that cytoimmunological monitoring is a useful, non-invasive additional method for diagnosing the first period of acute rejection after heart transplantation and that quantitative birefringence measurements give valuable information on the extent of myocyte damage.

Birefringence↗
PubMed1989

Lymphocyte status in endomyocardial biopsies and blood after heart transplantation.

We performed immunological phenotyping of mononuclear cells in tissue sections of 84 endomyocardial biopsies (EMB) showing infiltrates, which were taken from 21 patients after heart transplantation. Data were correlated with histology (grading following Billingham) and cyto-immunologic monitoring (CIM) on blood samples (grading into negative, rejection, or infection, based on leukocyte morphology and T-cell phenotype). Few T lymphocytes were observed in 35 biopsies, and many in 49 biopsies. The semi-quantitative estimate of T cells and CD4/CD8 ratio did not correlate with EMB histology but was related to CIM data. For example, 31 out of 42 cases with a CIM indicative of infection (14 of which showing no rejection on histology) manifested large numbers of T cells. In most cases, the CD4/CD8 ratio was less than 1. The presence of activated cells (bearing interleukin-2 receptors or the CD30 antigen) was not related to EMB histology or to CIM data. The number of T cells (subsets) in EMB was not related to relative or absolute numbers in the blood.

Biopsy↗
PubMed1989

Membranoproliferative glomerulonephritis in a patient with congenital deficiency of the third component of complement: effect of treatment with plasma.

A 21-year-old woman with a known congenital complement component 3 (C3) deficiency developed membranoproliferative glomerulonephritis. The kidney biopsy exhibited deposits of immunoglobulins and complement components despite the C3 deficiency. The administration of fresh frozen plasma was without therapeutic benefit. Corticosteroid treatment was followed by an improvement in kidney function.

Adult↗
PubMed1988

Coagulation screen is more specific than the anticardiolipin antibody ELISA in defining a thrombotic subset of lupus patients.

In 111 lupus patients we compared the potential of the IgG and IgM anticardiolipin antibody (ACA) enzyme linked immunosorbent assay (ELISA) and four different lupus anticoagulant (LAC) assays (partial thromboplastin time (PTT) of a 1:1 mixture of patient and control plasma with phospholipids from animal (PTT-st) or human brain (PTT-HB); PTT with dilutions of human brain phospholipids (PL dilution); and kaolin clotting time of mixtures of patient and control plasma (KCT] to identify patients with thrombosis (26/111), fetal loss (19/46), and/or thrombocytopenia (11/106). The highest specificity for thrombosis (87%) was found with PTT-HB and PL dilution (sensitivity 65%, detection rate 61%); for fetal loss (93%) with PL dilution (sensitivity 47%; detection rate 82%), and for thrombocytopenia (83%) with KCT (sensitivity 82%; detection rate 36%). Compared with LAC assays, the sensitivity of ACA-ELISA was high (greater than or equal to 77%), but specificity (less than or equal to 51%) and detection rate (less than or equal to 52%) were low. So, a panel of three LAC assays (PTT-HB, PL dilution, and KCT) can identify lupus patients apparently at risk for thrombosis, fetal loss, and/or thrombocytopenia, whereas the ACA-ELISA is insufficiently specific.

Adolescent↗
PubMed1987

Putative role of antireticulin antibody in antiacetylcholine-receptor-antibody-negative myasthenia gravis.

It has recently been demonstrated that pathogenic immunoglobulins circulate in the blood of patients with acetylcholine-receptor-antibody (A-AChR)-negative myasthenia gravis (MG). Evidence has been presented that in this form of MG the neuromuscular transmission is impaired by antibodies that bind to endplate determinants other than the AChR. We describe three patients with clinical manifestations of A-AChR-negative MG in whom antibody directed to reticulin (A-Ret) was detected. Antibody directed to reticulin is usually associated with celiac disease; however, none of the patients had symptoms or signs of celiac disease. To our knowledge, the association of A-Ret with A-AChR-negative MG has not been reported before. We postulate that A-Ret might help to differentiate between A-AChR-negative MG and congenital myasthenia. Further studies are needed to determine whether A-Ret plays a pathogenic role in A-AChR-negative MG or should instead be considered as an epiphenomenon.

Adult↗
PubMed1987

Influence of cytomegalovirus infection on the recovery of humoral immunity after autologous bone marrow transplantation.

Recovery of B-cell number and function was studied in 23 patients with hematological malignancies treated with high-dose chemoradiotherapy followed by autologous bone marrow transplantation (auto-BMT) in relation to the presence or absence of cytomegalovirus (CMV) infection. B cells recovered rapidly after auto-BMT and specific antibodies to herpes viruses remained nearly unchanged. Both were independent of the CMV status of the patients. However, the capacity of peripheral blood B cells to differentiate in vitro into cytoplasmic immunoglobulin (Ig)-positive cells (plasma cells) on pokeweed mitogen stimulation in the presence of normal T-cell help was significantly better in CMV-negative patients than in CMV-positive patients after auto-BMT, but was decreased in both groups. Serum Ig levels were, in contrast, higher in CMV-positive patients than in CMV-negative patients after auto-BMT.

Antibodies, Antinuclear↗
PubMed1986

Inhibition of adenovirus DNA replication in vitro by autoimmune sera.

Sera from patients suffering from autoimmune diseases were analyzed for the presence of antibodies that inhibit adenovirus DNA replication in vitro. DNA replication was studied in a reconstituted system containing purified viral proteins (DNA binding protein, DNA polymerase and the precursor to the terminal protein) and a crude nuclear extract from HeLa cells. About half the autoimmune sera analyzed inhibited DNA replication by more than 50% while only 2 out of 31 control sera showed strong inhibition. The inhibition was caused by the IgG fractions of the sera and was most frequently observed with sera from scleroderma patients. Several lines of evidence indicate that the inhibition is not due to anti-DNA antibodies. The mechanism of inhibition of two strongly inhibitory sera was further investigated. The IgG fractions from these sera blocked DNA chain elongation more than 80% but had no effect on the initiation step or the synthesis of the first 26 nucleotides. Using a dot blot assay and different incubation conditions, evidence was obtained that the inhibition is due to immunorecognition of a nuclear factor from HeLa cells. Two nuclear proteins are known to be required for adenovirus DNA replication, nuclear factors I and II. DNA replication in the presence of purified nuclear factor I instead of a crude nuclear extract was only slightly inhibited by the antisera. In agreement with this, immunorecognition of nuclear factor I could not be detected using a dot blot assay. Since nuclear factor II is not required in our assay system, these results suggest the existence of another nuclear component involved in adenovirus DNA replication which is neutralized by these antibodies.

Adenoviridae↗
PubMed1986

Implantation of cultured thymic fragments in patients with acquired immunodeficiency syndrome.

Cultured thymic fragments were implanted in one patient with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and in eight AIDS patients with opportunistic infections (OIs, four patients), Kaposi's sarcoma (KS, two patients), or both (two patients). Thereafter, objective clinical improvement was noted in one patient with OI, and a stable symptom-free condition was observed in the ARC patient and in two other patients with OIs. However, the ARC patient and two of the three patients with OIs developed infections three to six months after implantation. A fourth case of OI and the patients with KS showed progression of the disease. Peripheral blood investigations for counts of total leukocytes, lymphocytes, and T-lymphocyte subsets as well as for lymphocyte stimulation with mitogens showed no changes interpretable as an improvement of the cellular immune deficiency status. We conclude that cultured thymic fragments have no distinct in vivo effect on the course of AIDS, except for a temporary clinical improvement or a period of stable condition in some patients with OIs.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Cultured human thymus epithelial monolayer cells induce CD4 expression on mononuclear cells of AIDS patients in vitro.

We investigated the in vitro effect of cultured human thymic epithelial monolayer cells on mononuclear cells (MNC) from patients with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-related complex (ARC). Patients having undergone bone-marrow transplantation (BMT), who showed a similar deficiency of T-lymphocytes expressing CD4 (Leu-3, T4), and healthy blood donors served as controls. Most epithelial monolayer cells were of thymic medulla origin, as documented using a panel of monoclonal antibodies to thymic epithelial cells. In AIDS/ARC patients the CD4-positive cells (ranging between 4 and 30% of MNC) increased by a factor of 1.56 (s.e.m. 0.15, n = 12) during a 2 h incubation on the monolayer. Human fetal lung fibroblasts were inactive in this respect. There was no consistent change in cells expressing CD3 (Leu-4, T3), CD5 (Leu-1) or CD8 (Leu-2, T8). In BMT patients and healthy controls, neither thymus epithelium nor fibroblasts had any effect on T cell marker expression. Incorporation of tritiated thymidine by stimulated or unstimulated lymphocytes was increased after incubation for 3 days on either epithelium or fibroblasts. We conclude that CD4 expression is induced on MNC from AIDS/ARC patients during a 2 h incubation on epithelial monolayers.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Actinic reticuloid simulating Sézary syndrome. Report of two cases.

A report is given on two male patients who showed all the main characteristics of Sézary syndrome (SS). When phototested, however, they proved to be extremely photosensitive, which suggested a diagnosis of actinic reticuloid (AR). This was supported by the predominance in blood and skin specimens of lymphoid cells with a suppressor/cytotoxic phenotype, the absence of clonal cell proliferation and a benign clinical course. Differential diagnostic problems of SS and erythrodermic AR are discussed.

Aged↗