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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 649 records · Page 36Linked to original sources

[Value of long-term ECG in patients with syncope].

In a prospective study 24 hour long-term ECG (LT-ECG) recordings under ambulatory conditions were performed in 126 patients with syncopes (SY) of unknown origin. LT-ECG revealed arrhythmias (AR) in 57%, whereas 43% had inconspicuous findings. One patient developed a SY during LT-ECG without any evidence for arrhythmias. In 40% of these patients AR not detected previously by other methods were discovered. In 36% AR detected by LT-ECG had to be considered as precursors of syncopes (i.e. bradycardia less than 40 b.p.m., tachycardia greater than 160 b.p.m., AV-block II/II and III, or ventricular arrhythmias Lown IV). LT-ECG increased the information about the cause of syncope in 35%, whereas in 65% LT-ECG did not produce any further information. Consequently LT-ECG led in 56% to drug therapy, in 8% to PM-implantation. During a mean follow-up of 22 months 22% of patients developed again a syncopal attack and 4% died suddenly. Despite LT-ECG recording an ECG-registration during a typical syncopal attack for the confirmation or exclusion of an arrhythmogenic genesis of the SY is achieved only by chance. Nevertheless further informations with regard to precursing AR can be obtained, which may lead to therapeutic consequences in some patients. Therefore, LT-ECG has to be recommended as an essential, non-invasive procedure in patients with SY of unknown origin.

Adolescent↗

Hexachlorobenzene content in human whole blood and adipose tissue: experiences in environmental specimen banking.

By making use of material held in the Environmental Specimen Bank for Human Tissue Muenster (University of Münster, FRG), up to 11 organochlorine pesticides were analysed in organs (whole blood and adipose tissue) of living people, using real-time monitoring, and in autopsy material (up to 35 organs). The hexachlorobenzene (HCB) contents in whole blood samples of two comparable 'normal' populations (age 20-30 years, n = 118 and 125) were: median 2.30 micrograms/l, range 0.05-13.5 micrograms/l in 1977 and median 3.55 micrograms/l, range 0.94-16.3 micrograms/l in 1982. Females showed a slightly higher range than males. A pesticide-exposed group of wine growers (n = 122) showed a range of 0.86-29.6 micrograms/l with a median of 7.34 micrograms/l. In autopsy material, age-dependent HCB concentrations were found in adipose tissue, increasing with age (total range 0.14-45.4 micrograms/g extractable lipids, n = 80). No age dependence was evident in other organs. In starving people there seems to be only a slight elimination, if any, of the stored organochlorinated compounds. Persistent pesticides remain in a smaller portion of lipids and simulate higher values. Investigations of long-term storage of liver, fatty tissue and whole blood in the Environmental Specimen Bank (-85 degrees C and -170 degrees C) showed sufficient stability of HCB and other xenobiotics.

Adipose Tissue↗

HLA-DR-, MB- and novel DC-related determinants restrict purified protein derivative of tuberculin (PPD)-stimulated human T cell proliferation.

Class II major histocompatibility complex determinants restricting recognition of tuberculin antigens (purified protein derivative; PPD) were studied by using monoclonal antibodies (mAb) to block lymphoproliferative responses. Anti-class II mAb were shown to exert inhibitory effects at the level of the antigen-presenting cells, without inducing suppressive lymphocytes or macrophages. Using panels of HLA-typed antigen-presenting cells and nonalloreactive proliferative T cell lines, derived by limiting dilution, restriction elements for PPD responses appeared to correlate with the donor's HLA-DRw6 specificity (one clone), MB1 (one clone), MB3 (one clone), or no established class II (or class I) specificity (three clones). mAb TU22, reacting with nonpolymorphic DC-like determinants, strongly inhibited stimulation of all clones except that restricted by DR antigens, suggesting the DC-like character not only of the MB1- and MB3-associated, but also of the unassigned, restriction elements of these cloned lines. In contrast, stimulation of the DR-restricted line was strongly inhibited by DR/SB-specific mAb which only weakly inhibited the stimulation of clones restricted by DC-like determinants. These results suggest that clonally distributed PPD-reactive proliferative lymphocytes from a single donor may be restricted by at least three different class II determinants (HLA-DR, MB, or a second, novel, DC-related molecule).

Antibodies, Monoclonal↗

Refinement of HLA gene mapping with induced B-cell line mutants.

The lymphoma cell line BJAB.B95.8.6 was gamma-irradiated to induce mutations of major histocompatibility complex (MHC) encoded genes. Cloned "wild-type" cells were phenotyped HLA-A1, A2, B13, B35, Bw4, Bw6, Cw4, DR5, DRw52, DQw1, DQw3, DPw2, DPw4, GLO1 1, PGM3 2-1, and ME1 0 and possessed two apparently normal chromosome 6s prior to mutagenesis. Loss mutants were selected 5 days after 3 Gy gamma-irradiation employing three complement-fixing monoclonal antibodies specific for HLA-A2 (TU101) and Bw4 (TU48, TU109). Fifteen independently arising mutants were isolated and cloned. Typing with monospecific alloantisera and cell-mediated lympholysis revealed the presence of HLA-A1, B35, Bw6, Cw4, DR5, DRw52, DQw3, and DPw4 specificities on all mutant clones. HLA-A2, B13, and Bw4 were absent. Mutants differed in their expression of class II antigens. One group retained DQw1 and DPw2, another was DQw1-, DPw2+, and a third was DQw1-, DPw2-. Karyotyping of the "wild-type" line and selected mutant clones showed that the loss of HLA specificities correlated with deletions which map the HLA-A and -B loci directly to the distal part of the 6p21.33 region and the class II genes to the region 6p21.33 (proximal) to 6p21.31 (distal) on the short arm of chromosome 6.

Antibodies, Monoclonal↗

Characterization of a monoclonal anti-Bw4 antibody (Tü109): evidence for similar epitopes on the Bw4 and Bw6 antigens.

The production and serologic, as well as immunochemical properties of a cytotoxic murine IgG monoclonal antibody (Tü109) that precipitates HLA-class I molecules, are described. In the microcytotoxicity assay Tü109 supernatant was demonstrated on a panel of 424 HLA-ABC, -DR, -DQ, -MT typed normal Caucasian blood donors to define an epitope on HLA-B locus molecules in great association with the supertypic specificity Bw4. Reactivity of supernatant showed MHC linked inheritance of the Tü109 determinant and discriminated the HLA-Bw4/Bw6 associated HLA-B locus split antigens. Weak or lack of binding on lymphocytes from some HLA-Bw4 heterozygous individuals, particularly typing for HLA-Bw44, appeared to be due to qualitative and/or quantitative variations of HLA-B locus molecules on the cell surface. With Tü109 ascites fluid, however, extra-reactivity on all HLA-Bw6+ cells was demonstrated. Preferential binding of supernatant to HLA-Bw4, but reactivity of ascites fluid with HLA-Bw6+ molecules in addition, was furthermore confirmed by IEF analysis of antigens immunoprecipitated with Tü109 from cell lysates. Thus the antibody may help to analyze the evolutionary relationship of the diallelic specificities Bw4 and Bw6.

Antibodies, Monoclonal↗

Monosomy 6 in a human lymphoma line induced by selection with a monoclonal antibody.

The human Epstein Barr Virus-superinfected B lymphoma cell line BJAB-B95.8.6 was mutagenized by gamma irradiation, and HLA mutants were selected with the HLA-Bw6-specific monoclonal antibody SFR8-B6. One of the mutants obtained, BM19, had lost one of the chromosomes 6 present in the wild type cells. Electrophoretic analysis of phosphoglucomutase isozyme PGM3 and erythrocyte glyoxalase 1 from both cells supports this conclusion. The HLA antigens expressed on BM19 were HLA-A2, B13, Bw4, C-, DR2 (questionable), DRw52 (weak) and DQw1. This constitutes one of the haplotypes of the wild type cells, the other (lost from BM19 cells) being HLA-A1, B35, Bw6, Cw4, DR5, DRw52 (strong) and DQw3. Possibilities to employ BM19 cells for the analysis of the major histocompatibility complex and other chromosome 6-encoded genes as well as their products are discussed.

Antibodies, Monoclonal↗

Divergent expression of HLA-DC/MB, -DR, and -SB region products on normal and pathological tissues as detected by monoclonal antibodies.

A group of eight monoclonal antibodies directed against different monomorphic determinants of HLA-class II molecules was used to investigate the distribution of HLA-DC/DS/MB, -DR and -SB-like antigens on normal and pathological lymphoid and nonlymphoid tissues of human adult and fetal donors. HLA-MB/DC/DS-like molecules, as defined by the antibody TU 22, showed the most limited distribution as they were detected on B-lymphocytes, monocyte/macrophage subpopulations and distinct interstitial cells of various organs. HLA-DR and -SB-like antigens characterized by the other anti-HLA-class II reagents (TU34, TU35, TU37, TU39, TU43, TU58) were also present on these cell types. However, selective expression of HLA-DR and/or -SB like molecules was demonstrated with these antibodies on certain vascular endothelia, as well as different B-cell lymphomas and distinct epithelial cells in adults. Exclusive reactivity of the antibody TU39 shown on endothelial cells of fetal liver and kidney suggested specific functions of HLA-SB antigens during ontogeny. Furthermore, HLA-DR and/or -SB like molecules but not TU22+ HLA-DC/MB antigens were found to be inducible on normally Ia-like antigen negative epithelial cells of various diseased organs. Implications of this differential tissue distribution of HLA-DC/MB/DS, -DR and -SB like products in relation to organ transplantation, regulation of immune responses and cell differentiation are discussed.

Adult↗

Expression of HLA-A and -B antigens on differentiating U-937 cells.

Cells from the human immature monocytoid cell line U-937 were induced with 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) to differentiate towards macrophage-like cells. The expression of HLA-antigens during differentiation was examined with a panel of monoclonal antibodies directed against monomorphic and polymorphic determinants. Class II antigens could be detected neither on uninduced nor on TPA-induced U-937 cells. While the expression of HLA-A3 did not change significantly during differentiation, the "supertypic" specificities HLA-Bw4 and Bw6 as well as the "private" specificity HLA-B18 could be detected only on a drastically decreased number of cells after 4 days of exposure to TPA. This may imply a selective loss of HLA-B molecules from the cell membrane and therefore a separate regulatory control of HLA-A and -B antigens.

Cell Differentiation↗