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Biomedical subjects

B Heilig

Publications and source records attributed to B Heilig.

30 records · Page 2Linked to original sources
PubMed1990

Activation of lymphocytes induced by recombinant human granulocyte-macrophage colony-stimulating factor in patients with malignant lymphoma.

To investigate effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high-dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation.

Antigens, CD↗
PubMed1989

Evidence for immunological differences between circulating and thyroid tissue-derived thyroglobulin in men.

The expression of six antigenic epitopes on plasma Tg and tissue-derived Tg was investigated using mouse mabs in immunoradiometric assays. The sensitivity of the assays ranged between 0.5 and 1.5 micrograms l-1. Plasma thyroglobulin of 15 normal individuals and 18 patients with metastatic, differentiated thyroid cancer was analysed. Whereas five monoclonals produced values comparable to the conventional RIA system, the monoclonal antibody Tg 158 did not detect any Tg in the normal individuals and only low levels in two of the cancer patients with the highest Tg levels. In contrast, dilutions of extracts of three different euthyroid goitre samples and three different samples of differentiated thyroid cancer revealed no difference in the antigenic expression of all six epitopes, including the Tg 158 epitope. Papain digestion of purified Tg resulted in a 76 kD fragment which showed immunoreactivity for Tg 158 as well as for Tg 11. No interference of the binding of Tg 158 by T3, T4 or DIT could be detected. We conclude that the monoclonal antibody Tg 158 detects an epitope which is present in thyroid tissue-derived Tg but not in circulating thyroglobulin. This antibody might be useful for the investigation of the secretory process of thyroglobulin from the thyrocytes into the circulation.

Antibodies, Monoclonal↗
PubMed1988

Surveillance of diagnostic and treatment measures in Bavaria, 1974-1976. Results 2 and 5 years after the start of chemotherapy.

A central surveillance register for all bacillary pulmonary tuberculosis cases reported in Bavaria (population in excess of 10 million) was established from 1974 to 1976. The aim of the study was to discover the quality and efficiency of health services delivery to the population in the field of tuberculosis under routine conditions, and to find out the relapse rate after cessation of chemotherapy in expatients who were found to be negative 2 years after starting chemotherapy. A total of 7850 German patients with bacillary pulmonary tuberculosis were diagnosed in Bavaria from 1974 to 1976 corresponding to an average annual rate of 25.7 per 100,000 population: 71% of them were smear-positive and 29% were positive by culture only. Reactivations formed 25% of all bacteriologically confirmed cases. Most (71%) smear-positive new cases were discovered because of symptoms. Of the 5157 cases of bacteriologically confirmed pulmonary tuberculosis reported during 1975 and 1976, 4% died from tuberculosis, 1% from sequelae of tuberculosis and 9% from causes other than tuberculosis. A further 3% of patients had drug side-effects, 3% were uncooperative, 2% emigrated or had no permanent address and 1% had no chemotherapy or no information on treatment. The overall results of treatment were very satisfactory: sputum conversion among 3991 patients in the group with complete treatment was achieved in 97.4% at 2 years, and in those with incomplete treatment in 96.2%. The duration of chemotherapy was long, i.e. 19 months or more in two thirds of the patients. The average reactivation rate during the 3rd, 4th and 5th follow-up years was 0.8% annually; it was higher among males than females and the rate increased with age. Of the 157 patients found to be bacteriologically positive at 2 years after the start of chemotherapy 46 died during the 3-year observation period and 109 were alive at 5 years, 23 of whom were harbouring tubercle bacilli.

Adult↗
PubMed1988

Development of immunoradiometric assays for human thyroglobulin using monoclonal antibodies and the biotin/avidin system.

Monoclonal antibodies against human thyroglobulin were produced by the hybridoma technique. Using three non-crossreactive monoclonal antibodies, an IRMA system was developed, with a polyclonal rabbit antibody fixed on microtiter plates as first extracting antibody. The monoclonal antibodies were used as second antibody, while anti-mouse IgG-biotin from goat and [125I]streptavidin served as the indicator system. The source of the monoclonal antibodies was diluted culture medium without purification. Sensitivities of 3-4 micrograms/l were obtained with all 3 monoclonal antibodies; interassay variation was about 5%. This test system will be used for further immunological characterization of circulating thyroglobulin in different thyroid diseases.

Antibodies, Monoclonal↗
PubMed1988

Comparative plasma thyroglobulin measurements with three non-cross-reactive monoclonal antibodies in metastatic thyroid cancer patients.

In 12 normal individuals and 25 patients with metastases of differentiated thyroid cancer, plasma thyroglobulin (Tg) concentrations were measured simultaneously with three immunoradiometric assays. Each of the three systems used a different, non-cross-reactive monoclonal Tg antibody as second antibody. In general, there was a very close correlation between the results of the three different systems in the cross-sectional study of the 25 cancer patients as well as in longitudinal follow-up studies in selected patients. The monoclonal antibody Tg 40 produced values about 30% higher than the two other systems. The difference was, however, not statistically significant owing to the large scatter. The monoclonal antibody Tg 13 appeared to be very sensitive to interference with thyroglobulin autoantibodies. In conclusion, the monoclonal antibodies against the three epitopes tested produced very similar Tg values in normal individuals and 25 patients with metastatic thyroid cancer; however, before more is known about epitope specificity of Tg autoantibodies and heterogeneity of tumour Tg, monoclonal antibodies should be used for routine measurements only with caution.

Antibodies, Monoclonal↗
PubMed1986

Increased heterogeneity of serum thyroglobulin in thyroid cancer patients as determined by monoclonal antibodies.

We investigated the immunological heterogeneity of plasma Tg in thyroid cancer patients using monoclonal antibodies in an immunoradiometric assay and a conventional RIA system with a polyclonal rabbit antibody. The results were compared with measurements of plasma Tg in patients with nonmalignant disease. We can demonstrate an increased immunological heterogeneity in tumor patients compared with patients with non-malignant thyroid diseases. In one case the Tg value measured by a monoclonal test system exceeded the value obtained by a polyclonal RIA system in the same sample by a factor of 25. It has to be further investigated whether this increase in heterogeneity is of diagnostic value in the follow-up of thyroid cancer patients.

Adenocarcinoma↗
PubMedDate not supplied

[Plasma GM-CSF concentrations in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy].

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent hematopoietic growth factor, which is mainly produced by T-cells and stromal cells. Beside the stimulating effects on mature granulocytes, it induces the expression of HLA class II-antigen on synovial tissue-cells in patients with rheumatoid arthritis. The concentrations of GM-CSF in the plasma of 87 patients with rheumatoid arthritis, 48 patients with spondyloarthropathy, 17 patients with systemic lupus erythematosus (SLE), and 43 healthy control persons were investigated. We used an immunoradiometric assay (IR-MA) with a detection limit of 30 pg/ml to measure the GM-CSF concentrations in plasma. The GM-CSF levels of 29 patients with severe rheumatoid arthritis (366 +/- 61 pg/ml, p less than 0.05), 58 patients with moderate rheumatoid arthritis (376 +/- 44 pg/ml, p less than 0.0001), and of 17 patients with SLE (256 +/- 41 pg/ml, p less than 0.05) were elevated compared to the control group (174 +/- 18 pg/ml). No significant differences in the mean GM-CSF plasma levels between the patients with spondyloarthropathy (190 +/- 32 pg/ml) and the control group were found. GM-CSF concentrations as high as 1300 pg/ml were detected in the synovial fluids of patients with rheumatoid arthritis. GM-CSF concentrations in the plasma of patients with severe rheumatoid arthritis were correlated with the plasma concentrations of the soluble interleukin-2-receptor (sCD25) (R = +0.53).

Arthritis, Rheumatoid↗
PubMedDate not supplied

[Expression of TNF receptors in rheumatoid arthritis and ankylosing spondylitis].

Tumor necrosis factor is an important mediator of the pathophysiologic events in synovitis. The expression of the p75 and p55-TNF-receptors in rheumatic diseases was investigated. Synovial mononuclear cells (SMNC) of patients with rheumatoid arthritis and spondylarthropathies express p75 TNF receptors in all cases, whereas SMNC of patients with traumatic synovitis do not. In 4/9 patients with rheumatoid arthritis and in 6/11 patients with spondylarthropathies SMNC also expressed the p55 TNF receptor. Differential analysis of lymphocytes and monocytes/macrophages revealed that both predominantly expressed the p75 TNF receptor. The highest concentrations of both soluble TNF receptors which may act as TNF antagonists were found in synovial fluids of rheumatoid arthritis patients.

Arthritis, Psoriatic↗