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Biomedical subjects

M Pfreundschuh

Publications and source records attributed to M Pfreundschuh.

209 records · Page 12Linked to original sources
PubMed1977

Sensitive radioimmunoassay for thyrotropin by use of commercially available tracer and antibody.

The time course of the association and dissociation of radiolabeled thyrotropin with its antibody was studied. The binding is maximal after five days of incubation. The dissociation is much slower. Highest sensitivity is obtained by a total incubation time of five days with addition of the labeled ligand after three days of preincubation with the unlabeled thyrotropin. An improvement in the sensitivity from 0.4 mU/l to 0.08 mU/l is obtained by that method compared with equilibrium technique thus significantly diminishing the percentage of undetectable serum levels of euthyroid and hyperthyroid subjects. Average sensitivity is 0.14 mU/l, intraassay variance is 2%, interassay variance is about 13% in the normal range. Normal values for euthyroid subjects averaged 1.53 mU/l, for hyperthyroid subjects 0.19 mU/l.

Dose-Response Relationship, Immunologic↗
PubMedDate not supplied

Increased levels of circulating interleukin-6 in patients with Hodgkin's disease.

Expression of interleukin-6 (IL-6) and IL-6 receptors has been demonstrated in Hodgkin and Reed-Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL-6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL-6 was only rarely detectable in healthy controls or patients with non-Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL-6 levels (range 12-32 pg/ml). The rates of detectable IL-6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B-symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL-6-negative and IL-6-positive patients. Except in one of 23 follow-up sera taken after therapy, IL-6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL-6.

Adolescent↗
PubMedDate not supplied

Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody.

A group of 15 patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural-killer (NK)-cell-activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's associated CD30 antigen. The antibody was given four times every 3-4 days, starting with 1 mg/m2. The treatment was well tolerated and the maximum tolerated dose was not reached at 64 mg/m2. Side-effects were rare and consisted of fever, pain in involved lymph nodes and a maculopapulous rash. Nine patients developed human anti-(mouse immunoglobulin) antibodies. One complete and one partial remission (lasting 5 and 3 months, respectively), three minor responses (1 to 11+ months), and one mixed response were achieved. There was no clear-cut dose side-effect or dose/response correlation. NK cell activity increased in most of the patients treated with 4 mg/m2 or higher doses but lasted no longer than 6 weeks after therapy. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the antibody to allow retreatment of responding patients.

Adult↗
PubMedDate not supplied

Binding of monoclonal anti-interleukin 2 antibody to nucleoli in acute leukemia blast cells.

Neutralizing anti-IL-2, anti-IL-3, and anti-IL-6 monoclonal antibodies (MAbs) were used for the immunoenzymatic detection of the respective cytokines in blast cells of 38 patients with acute myeloid (AML) and lymphoid (ALL) leukemias by the APAAP-technique. In 20/24 AML-cases (83%) blast cells showed intranuclear staining with MAb anti-IL-2 (DMS-1). In 17 cases reaction was restricted to the nucleoli, in 4 cases additional cytoplasmic staining was observed. Only 2/13 (15%) of the ALL cases showed anti-IL-2 staining. In contrast to IL-2, neither IL-3, IL-6 nor IL-2R alpha-chains were detected in any of the acute leukemias tested. The anti-IL-2 staining of nucleoli in AML cells is distinct from the cytoplasmic staining which is observed in PHA-activated normal lymphocytes and in a minority of AML cells.

Antibodies, Monoclonal↗
PubMedDate not supplied

Idiotype vaccine against Hodgkin's lymphoma: generation and characterization of an anti-idiotypic monoclonal antibody against the Hodgkin-associated (anti-CD 30) monoclonal antibody HRS-3.

The murine monoclonal antibody HRS-3 (Ab1; isotype IgG1-Kappa), that defines the CD30 antigen (m.w. 120,000) expressed by Hodgkin-Reed Sternberg cells was used to generate monoclonal anti-idiotype antibodies (Ab2) in syngeneic BALB/c mice. Ab2 were selected on the basis of their binding to HRS-3 immunoglobulin and F(ab')2 fragments and lack of reactivity with the whole immunoglobulin or F(ab')2 fragments of unrelated monoclonal antibodies of the same isotype and allotype. Such a putative anti-idiotypic Ab2, was designated antibody 12D3 and further characterized. 12D3 bound to the paratope of HRS-3, as determined by a 85% inhibition of binding of biotinylated HRS-3 to the cell surface of the CD30 positive Hodgkin cell line L450, and to semipurified CD30 positive cell lysates thereof at a concentration as low as 50 ng/well. These results demonstrate that 12D3 binds at or near the binding site of HRS-3 to the CD30 antigen. Purified 12D3 was coupled to keyhole limpet hemocyanine and used to immunize BALB/c mice and rabbits in order to obtain an Ab3 which binds to the CD30 antigen. These immune sera inhibited the binding of biotinylated 12D3 with HRS-3. Moreover, they showed binding activity with the CD30 positive L540 Hodgkin cell line as well as with the L540 cell lysates, indicating that an anti-anti-idiotopic antibody (Ab3) shares idiotopes with Ab1 (HRS-3). These data suggest that antibody 12D3 may be useful in the generation of an anti-idiotype vaccine against Hodgkin's lymphomas.

Animals↗
PubMedDate not supplied

Hodgkin and Reed-Sternberg cell associated monoclonal antibodies HRS-1 and HRS-2 react with activated cells of lymphoid and monocytoid origin.

The two monoclonal antibodies HRS-1 and HRS-2, which were obtained after immunization with the Hodgkin's derived cell line L428, detect different epitopes on a 120 kd antigen. This antigen is present on Hodgkin- and Reed-Sternberg (H&RS) cells in all subtypes of Hodgkin's lymphoma and on large cell anaplastic non-Hodgkin's lymphomas. The H&RS- associated 120 kd antigen appears to be a non-lineage specific activation antigen, as it is not present on normal B and T lymphocytes or monocytes, but appears on these cells after activation. Because of their restricted reactivity with H&RS cells, HRS-1 and HRS-2 alone or in combination may be helpful for immunoimaging and immunotherapy of Hodgkin's lymphomas.

Animals↗
PubMedDate not supplied

The influence of chrysotherapy on T-lymphocyte subpopulations in rheumatoid arthritis.

We studied the influence of chrysotherapy on lymphocytes, B-cells, T-cells, and T-lymphocyte subpopulations in 9 rheumatoid-factor-positive female patients with rheumatoid arthritis (RA). After chrysotherapy, the white blood cell count decreased within 1 month; the percentage of lymphocytes, T-cells, and B-cells did not change significantly, nor did the proportion of helper cells as determined by reactivity with monoclonal antibody OKT4. In contrast, the percentage of suppressor T-cells reactive with OKT8 was significantly decreased (p less than 0.05) after 6 months. As a consequence, the helper/suppressor ratio, which was significantly higher than in age- and sex-matched controls (p less than 0.02), showed an even more pronounced deviation from normal values than before therapy. The implications of these findings in regard to a possible immunological mechanism of action of gold and the significance of the disturbance of the "immunoregulatory balance" between helper and suppressor mechanisms for the pathogenesis of RA are discussed.

Adult↗
PubMedDate not supplied

T-lymphocyte subpopulations in rheumatoid arthritis. II. Definition by monoclonal antibodies.

Samples of peripheral blood of 27 patients with seropositive rheumatoid arthritis (RA) and 27 healthy age- and sex-matched controls were coded and studied for lymphocyte subpopulations. Monoclonal antibodies and indirect immunofluorescence were used to analyse subpopulations of purified T cells: OKT3 reacts selectively with all peripheral human T cells, OKT4 defines the helper/inducer subpopulation and OKT8 the suppressor/cytotoxic T cells. RA patients had a significantly lower relative lymphocyte count (p less than 0.001). whereas the percentage of all T cells was similar in patients and controls, RA patients had a significantly higher proportion of helper/inducer cells (62 +/- 1.3 vs. 56 +/- 1.0, p less than 0.005) and significantly decreased suppressors/cytotoxic cells (25 +/- 1.5 vs. 32 +/- 1.0; p less than 0.001). This resulted in an increased "immunoregulatory ratio" of helper to suppressor cells in RA patients (2.68 +/- 0.17) compared to their normal controls (1.83 +/- 0.10; p less than 0.001). The proportions of T cells expressing HLA-D-like antigens (defined by a monoclonal antibody to human Ia) was not different in patients and controls. These findings confirm conclusions derived from our previous study of T cell subsets defined by the expression of Fe-receptors (Tm and Tg), that in the peripheral blood of patients with RA, helper mechanisms predominate over suppressor mechanisms. This derangement of the immunoregulatory balance may have an important role in the pathogenesis of seropositive RA.

Adult↗
PubMedDate not supplied

T-lymphocyte subpopulations in rheumatoid arthritis.

We studied 24 patients with rheumatoid arthritis and 24 age- and sex-matched controls for lymphocyte subpopulations in the peripheral blood. Patients with rheumatoid arthritis had a significantly lower relative lymphocyte count (p < 0.005) and a higher percentage of T lymphocytes bearing Fc-receptor for IgM (TM) (p < 0.05). The proportion of B lymphocytes, total T lymphocytes and T lymphocytes with Fc-receptors for IgG (TG) in patients with rheumatoid arthritis was not different from that in controls. In 1 of 5 cases tested incubation of T lymphocytes in autologous rheumatoid factor positive serum instead of FCS resulted in significant reduction of TM and increase in TG cells. These results are discussed in relation to possible immunological factors involved in the etiology of rheumatoid arthritis.

Adult↗