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Biomedical subjects

A Ziegler

Publications and source records attributed to A Ziegler.

At least 307 records · Page 17Linked to original sources

Do monoclonal antibodies Tü15 and Tü67 detect heterogeneity of human transferrin receptor molecules?

The possible molecular heterogeneity of human transferrin receptors was analyzed using two murine monoclonal antibodies, Tü15 and Tü67. Both reagents precipitated from lysates of 125I-labeled HL-60 cells a major component of 88 kDa which could be identified as the transferrin receptor by comparison with the proteins detected by monoclonal antibody OKT9. Although sequential immunoprecipitations appeared to demonstrate molecular heterogeneity of transferrin receptors, since the Tü15-reactive species were fully included in the Tü67-positive population, but not vice versa, the possible association of Tü15-reactive molecules with transferrin receptor is also discussed.

Antibodies, Monoclonal↗

[Interval therapy of migraine. Pharmacological bases].

A quite heterogenous variety of drugs is used for the prophylactic treatment of patients with severe migraine. These drugs may prove effective in preventing migraine attacks due to two different pharmacological effects: a reduction of platelets' aggregability and/or an effect on blood vessels tone. The latter effect may be characterized by a decrease in reactivity, i.e. vasoconstriction as well as an overshooting vasodilation is prevented. The vascular tone is stabilized.

Adrenergic beta-Antagonists↗

Cardiac glycosides with different effects in the heart.

Remarkable differences exist between the effects of different cardiac glycosides (native and semi-synthetic) with respect to the affinity and to the magnitude of inotropic responses and their time courses. At glycoside concentrations which lead to identical Na-K-ATPase inhibitions, the inotropic responses vary widely. This finding contradicts the hypothesis that the increase of contractile force is the consequence of an ATPase inhibition and causally related to it. We propose the hypothesis that the inhibition of ATPase and the inotropic stimulation provoked by cardiac glycosides are two parallel events, not causally related but both mediated by the same receptor. The inhibition of the Na-K-ATPase is the consequence of the occupation and thus proportional to the concentration of the glycoside-ATPase complexes. In contrast, the inotropic response is determined by the frequency of glycoside-ATPase-interactions. Glycosides which possess high association and dissociation rate constants will interact with the ATPase with high frequencies and thus will evoke larger inotropic responses at a given ATPase inhibition than glycosides with low turnover rates.

Animals↗

Psychomental stress in tetraplegic man: dissociation in autonomic variables and emotional responsiveness.

Tetraplegic patients with physiologically complete cervical spinal cord transsection are classic ablation models of sympathetic denervation. Therefore this study was conducted to investigate the hemodynamic response (blood pressure, cardiac rate) and the plasma catecholamine (adrenaline, noradrenaline) release induced by a standardized psychomental stress model (sonic confuser). Attention was focussed on subjective evaluation of stress experience in spinal man. During psychomental stress, typical pressure reaction was not observed, cardiac rate was elevated insignificantly, and catecholamine release was diminished. The subjective estimates of stress experience, however, did not differ from those of the control group. It appears that psychomental stress in sympathectomized man is not extinguished despite abolished peripheral autonomic feedback modifying the state of the central nervous system. Cognitive processes and cortical arousal seem to be the initial and important steps of emotional experience and they are independent from peripheral autonomic processes. These results lend support to the centralistic view of emotions and the importance of cognitive factors in emotional responsiveness.

Adult↗

The effect of gallamine, gallopamil and nifedipine on responses to acetylcholine and carbachol in the taenia of the guinea-pig caecum.

The effects of gallamine, gallopamil and nifedipine on isotonic contractions of the isolated taenia of the guinea-pig caecum produced by acetylcholine (ACh) or carbachol (CCh) were investigated. Gallamine (0.1 to 0.3 mM) inhibited contractions produced by CCh more than those produced by ACh. The difference was still present after pretreatment of the tissue with paraoxon (10 microM for 20 min) to inhibit cholinesterases or in experiments carried out in the presence of tetrodotoxin (0.3 microM) to exclude possible ganglionic stimulation by the agonists. Gallopamil or nifedipine selectively inhibited the tonic response to ACh in the absence or presence of paraoxon. The phasic response to ACh or the tonic response to CCh (0.1 or 1 microM) was much less affected. Reduction of the Ca2+ content of the bath medium reduced phasic and tonic responses to ACh more than the tonic response to CCh. These results suggest that there are differences in the interaction of ACh and CCh with muscarinic receptors in this muscle.

Acetylcholine↗

Immature sinus histiocytes. Their identification as a novel B-cell population.

The true nature of cells of "immature sinus histiocytosis" (ISH) is uncertain because they lack the typical features of normal histiocytes when analyzed by enzyme cytochemistry or electron microscopy. In the present study the antigenic profile of ISH cells has been analyzed by immunohistologic techniques in six cases of Piringer's lymphadenitis with the use of a large panel of monoclonal and polyclonal antibodies reactive with the major cell types of the hematolymphoid system. The results obtained indicate that ISH cells consistently lack markers found on cells of the monocyte/macrophage series, myeloid cells, interdigitating reticulum cells, follicular dendritic reticulum cells, T cells, or Ki-1-positive cells. They constantly express B-cell antigens and HLA-DR and (on a variable proportion of cells) surface immunoglobulin. The application of antibodies reactive with different B-cell subsets showed that the cells of ISH do not correspond to any previously described B-cell population, eg, pre-B cells, germinal center cells, follicular mantle lymphocytes, or marginal zone cells. Furthermore, ISH cells and germinal center cells are found in association with clearly different cell types. These findings indicate that ISH cells represent a B-cell population at a previously undescribed differentiation stage, occurring only under certain circumstances (eg, in toxoplasmosis or AIDS). It is proposed that the term "immature sinus histiocytosis" be replaced by "B-cell sinus reaction."

Antibodies, Monoclonal↗

[Properties of Hodgkin cell lines. Possible significance for pathophysiology and clinical medicine].

In the last three years, five permanently in-vitro growing cell cultures with malignant properties were established from tumour material of patients with histologically confirmed Hodgkin's disease. Four cell lines have been maintained in culture. L 428 had identical characteristics in every respect with Hodgkin and Sternberg-Reed cells, tested in-vivo on biopsy tissue. The other lines--L 538, L 540 and L 591 - had certain characteristics of Hodgkin and Sternberg-Reed cells with a number of markers, but were not fully congruent. All lines reacted with a heterologous antiserum against L 428, which selectively cross-reacted with Hodgkin and Sternberg-Reed cells in fresh biopsies. Two sublines, L 428 KS and L 428 KSA, were established from L 428 by modifying the culture medium. Tests on L 428 KS cells with conventional methods and with monoclonal antibodies demonstrated that this line carried antigens of myeloid cells; however, it could not be definitely placed into any haematopoetic line. Conditioned medium of L 428 and its sublines showed CSF activity (colony-stimulating factor) and suppression of cell-mediated cytolysis.

Acid Phosphatase↗

Quantitative and qualitative differences in the distribution of HLA class I antigenic determinants in the human thymic compartments.

The topographical distribution of HLA class I antigens has been investigated by the immunoperoxidase technique on normal frozen thymic tissue sections with a panel of mono- and polymorphic monoclonal anti-HLA antibodies. HLA class I framework determinants detected by the monoclonal antibody W6/32.HL were present on 80-90% of cortical thymocytes, as well as on all cortical epithelial and medullary cells. However the staining intensity of cortical thymocytes with this reagent was about threefold weaker than that of the medullary thymocytes. Labelling patterns of selected monoclonal antibodies against matching HLA-A/B allospecificities revealed striking variations in the quantitative expression of certain HLA-A vs. HLA-B locus alloantigenic determinants on cortical thymocytes compared to a consistent staining on almost all medullary cells.

Antibodies↗

Hodgkin's disease cell lines: characteristics and biological activities.

In the last 4 years we have established five long-term cultures from tumor material of Hodgkin's disease. The in vitro cells have malignant characteristics and represent the in vivo Hodgkin- and Sternberg-Reed-cells as shown by the identity of multiple properties. Common immunological, functional, and morphological assays did not characterize the in vitro cells as a known cell type of lymphoid, myeloid, or monocytoid tissue. The in vitro Hodgkin's disease cells are biologically active by producing factors involved in regulation and promotion of immunological response and granulopoiesis. The relevance of the findings for pathogenesis and clinical appearance of Hodgkin's disease is discussed.

Antibodies, Monoclonal↗

Phenotypic heterogeneity of leukemic Sézary cells.

Leukemic blood cells from eight patients with Sézary's syndrome were analyzed for enzyme cytochemical features, Fc receptors, and surface phenotype. Enzyme cytochemically the cases were heterogeneous in their activity of acid esterase, acid phosphatase and dipeptidylaminopeptidase IV (DAP IV). Only one case showed positive staining for DAP IV. The expression of Fc receptors for IgG and IgM also varied. The DAP IV-positive case exhibited Fc mu receptors. In contrast, four other cases showed only Fc gamma receptors. Analysis of the surface antigen pattern of Sézary cells with monoclonal antibodies revealed the phenotype of helper T lymphocytes (Leu-3 a/OKT4+) in all but one case. The Leu-3 a/OKT4-negative case showed a phenotypic feature of natural killer cells (Leu-7+). The results obtained with the antibodies TU14 and Anti-human Lyt-1 were more heterogeneous. The heterogeneity of Sézary cells may be interpreted as a sign of differences in functional differentiation or of proliferation of different T-cell subclones.

Acid Phosphatase↗

Human dendritic reticulum cells of lymphoid follicles: their antigenic profile and their identification as multinucleated giant cells.

The B-dependent areas of human lymphoid tissue contain non-lymphoid, non-phagocytic cells known as dendritic reticulum cells (DRC). These cells can be detected only very occasionally in routinely stained histologic sections. Recently we were able to overcome this limitation by preparing a monoclonal antibody, termed R 4/23, that reacts selectively with DRC. Thus by using an optimized immunoperoxidase method applied to frozen sections, it is possible to detect DRC in situ. To determine the antigenic profile of DRC, serial frozen sections of human tonsils were immunostained with R 4/23 and a large panel of other monoclonal antibodies or conventional antisera. In addition, touch imprints of tonsils and cytocentrifuge slides of cell suspensions with increased concentrations of DRC were immunostained with these reagents. DRC proved to be positive for mu, gamma, alpha, kappa and lambda chains, complement component C3b, C3b receptors, C3d receptors, HLA-A,B,C antigens, human Ia-like antigens, common ALL antigen (cALLa), and antigens that are characteristic of the monocyte/macrophage lineages. DRC did not express delta chains, T cell antigens, or antigens that are expressed on interdigitating reticulum cells (IDC) and Langerhans cells. DRC in touch imprints and suspensions prepared from hyperplastic tonsils were found to be giant cells often with 10 or more nuclei. In certain cases of follicular hyperplasia and of centroblastic-centrocytic lymphoma, DRC with several nuclei were also detectable in situ. These results show that (1) the phenotype of DRC differs from that of all other cell types in lymphoid tissue, (2) this phenotype most nearly resembles that of cells of the monocyte/macrophage series, thus suggesting that DRC are related to these cell lineages, and (3) DRC are multinucleated giant cells.

Antigens↗

A cytotoxic monoclonal antibody specific for the private alloantigenic determinant of the HLA-B 13 molecule.

A murine monoclonal antibody (TU 110) prepared against blast cells of a patient with acute "undifferentiated" leukemia was tested in the microcytotoxicity assay on peripheral blood lymphocytes of 122 normal Caucasian donors. The TU 110 reactivity was found to show a correlation coefficient of 1.0 in population analysis for the presence of the HLA-B locus specificity B 13 as defined by alloantisera. Family segregation studies confirmed MHC linked inheritance of the TU 110 antigenic determinant strictly on HLA-B 13 positive haplotypes. As the first monoclonal reagent against the private specificity of this HLA-B locus antigen, TU 110 provides the possibility to study the structural relationships of sub- and supertypic determinants on this allotype and may help to correlate antigenic domains of HLA-B 13 with definable functional properties.

Animals↗

A cytotoxic monoclonal IgM antibody (Tü 101) directed against an antigenic determinant shared between the HLA-A allospecificities A2 and A28.

A complement-fixing murine monoclonal IgM antibody (TU 101) strictly directed against a supertypic determinant present on the HLA-A locus antigens A2 and A28 was defined from a fusion experiment employing T cell blasts as immunizing cells. The specificity of this antibody was established in the microcytotoxicity assay on 91 normal Caucasian blood donors, as well as in the SpA-Ig assay on a panel of lympho- and hematopoietic cell lines. TU 101 segregates only with its defined HLA allotypes in families. This reagent may be of particular value as a probe for analyzing a molecular relationship of different antigenic determinants on the HLA-A2 and A28 specificities in comparison with two recently defined anti-HLA-A2/A28 monoclonal antibodies and may help to characterize structural variations of these HLA-molecules on a serological and immunochemical basis.

Animals↗