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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 343 records · Page 19Linked to original sources
PubMed1995

Antibodies to heat shock proteins in patients with pulmonary sarcoidosis.

Serum concentrations of IgG, IgA, and IgM antibodies to three heat shock proteins (HSPs)--ubiquitin, HSP70, and HSP90--were measured using ELISA in 37 patients with pulmonary sarcoidosis. When compared to healthy controls (n = 44), increased concentrations of IgA and IgG antibodies to ubiquitin were found in 13 (35.1%, p < 0.002) and 7 (18.9%, p < 0.05) patients, respectively. In 10 patients (27.0%) elevated concentrations of IgG antibodies to HSP70 were detected (p < 0.02), whereas IgA antibodies to this protein were found in 7 cases (18.9%, p < 0.05). IgM antibodies to ubiquitin and HSP70, and antibodies to HSP90 were not detected in patients' sera. The levels of antibodies to ubiquitin and HSP70 correlated well with each other within the given immunoglobulin class (r = 0.7391, p < 1E-5 and r = 0.9854, p < 1E-5 for IgG and IgA class, respectively). There was also a weak correlation between the level of IgG antibodies to HSP70 and both serum activity of angiotensin converting enzyme (SACE; r = 0.4668, p < 0.005) and serum level of soluble receptor for interleukin 2 (sIL-2-R; r = 0.4142), p < 0.02). A similar tendency was seen with IgG antibodies to ubiquitin. Furthermore, there was an association between the increased concentration of C-reactive protein (CRP) and increased levels of IgG antibodies to ubiquitin and HSP70 (p < 0.005 and p < 0.05, respectively). Our results suggest that antibodies to various HSPs are present in a subset of patients with sarcoidosis. The humoral immune response to HSPs relates probably to the immune activation and/or infection.

Adult↗
PubMed1995

"In vitro" effect of Egyptian tannin-containing plants and their extracts on the survival of pathogenic bacteria.

This study was conducted on leaves from tannin containing plants which are widely spread in Upper Egypt. From two plants also fruits were investigated (A. nilotica and A. farnesiana). One of the objectives was to determine the total soluble polyphenols and the soluble condensed tannins of these plants. Furthermore the assumed antimicrobial effect of A. nilotica and A. farnesiana leaves and their extracts on C. perfringens, E. coli and S. typhimurium was studied "in-vitro" at dilutions of 0.5% and 0.05%. The tests were carried out in physiological saline solution and in rumen fluid medium (RFM). The results revealed that the total soluble polyphenols ranged from 10.27% to 35.46% and the condensed tannins from 0.5% to 8.28% on dry matter base. The antimicrobial effect of the plant material was only observed on C. perfringens but not on E. coli and S. typhimurium. A. nilotica leaves destroyed the suspension of C. perfringens immediately after being added. Leaves from A. farnesiana showed a delayed affect. Plant extracts were less effective than the raw plant material. In RFM A. nilotica leaves destroyed the bacterial suspension after 10 minutes only at the concentration of 0.5%, but not at 0.05%. With A. farnesiana at a concentration of 0.5% only a reduction was observed. The concentration of 0.05% had no influence. The presence of other proteins than bacterial suspension in rumen fluid (rumen bacteria, protozoa and plant proteins) inhibits the antimicrobial effect of the plant material in a concentration of 0.05%, but not at 0.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acacia↗
PubMed1995

High-frequency oscillatory ventilation and nitric oxide: alternative or complementary to ECMO.

One hundred and seventy-seven term or near-term neonates were referred to an ECMO center for severe PPHN-associated diseases. In 2 time periods from 1987 to 1991 and from 1992 to April 1995 alternative treatment modes were tried in an attempt to obviate ECMO. During the first time period patients underwent trial high-frequency oscillatory ventilation before ECMO. In the second time period patients first received inhaled NO followed by HFOV in a non-responders. If this also failed HFOV was combined with INO. In both time periods about 40% of the patients were spared ECMO treatment by these alternative treatment modalities. INO only benefited 15% of the ECMO candidates who apparently had fared just as well on HFOV alone in the preceding time period. While patients who were improved by INO were spared HFOV with its potential severe complications, i.e. air leaks and cardiocirculatory instability, more extended long-term studies will have to show which of these 2 treatment modalities (INO or HFOV) should be given first priority in an attempt to avoid ECMO in neonates with severe respiratory failure.

Administration, Inhalation↗
PubMed1995

Therapeutic effect of hyperbaric oxygenation in acute acoustic trauma.

Retrospectively 78 patients with uni- or bilateral acute acoustic trauma (AAT) were evaluated to assess the therapeutic effect of hyperbaric oxygenation (HBO). All subjects received saline or dextran (Rheomacodrex) infusions with Ginkgo extracts (Tebonin) and prednisone. Thirty six patients underwent additional hyperbaric oxygenation at a pressure of 2 atmospheres absolute for 60 minutes once daily. Both treatment groups were comparable as far as age, gender, initial hearing loss and prednisone dose are concerned. The delay of therapy onset was 15 hours in both groups and treatment was started within 72 hours in all cases. Control audiometry was performed after 6.5 days, when the HBO group had had 5 exposures to hyperbaric oxygenation. The average hearing gain in the group without HBO was 74.3 dB and in the group treated additionally with HBO 121.3 dB (P < 0.004). It is concluded, that hyperbaric oxygenation significantly improves hearing recovery after AAT. Therefore acute acoustic trauma with significant hearing threshold depression remains an otological emergency. Minimal therapy involving waiting for spontaneous recovery, which is mostly incomplete leaving a residual C5 or C6 and handicapping tinnitus, is not the treatment of choice. Randomized prospective clinical trials with a larger patient series are needed and further experimental studies are required to understand the physiological mechanisms of HBO responsible for the clinical success in AAT.

Acute Disease↗
PubMed1995

Interleukin 10 inhibits interleukin 6 production and acute phase response in rheumatoid arthritis.

To evaluate the effect of interleukin 10 (IL-10) on acute phase response, we determined serum levels of IL-10, interleukin 6 (IL-6), C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), alpha-1-anti-chymotrypsin (ACT) in 34 rheumatoid arthritis (RA) patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). CRP, AGP and ACT levels were measured using rocket immunoelectrophoresis. The results showed that IL-10 serum level was increased in RA patients as compared to controls (60.0 +/- 17.5 pg/ml vs. 7.2 +/- 1.9 pg/ml). IL-6 level was significantly elevated (87.3 +/- 32.7 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (34 +/- 19 mg/1 vs. 3 +/- 2 mg/1, p < 0.05). AGP and ACT serum levels were increased in RA patients, but we did not find these changes to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.73, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.74, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. Moreover, a negative correlation between IL-10 and serum level of CRP (r = -0.76, p < 0.05), AGP (r = -0.60, p < 0.05) and ACT (r = -0.37, p < 0.05) was also shown. According to the data thus far obtained it seems that IL-10 decreases IL-6 production, and by that indirectly affects acute phase response, decreasing CRP, AGP and ACT synthesis.

Acute-Phase Reaction↗
PubMed1994

Cre-loxP-mediated gene replacement: a mouse strain producing humanized antibodies.

BACKGROUND: The bacteriophage-derived Cre-loxP recombination system operates efficiently in mammalian cells. This system is particularly useful in gene-targeting experiments in the mouse, and has already been used to generate 'clean' deletions of target genes in the germ line, as well as to inactivate target genes in a conditional manner (based on regulated expression of the Cre recombinase). In principle, Cre-loxP-mediated recombination should also allow gene replacement, and thus the introduction of virtually any kind of mutation into the genome. RESULTS: We used the Cre-loxP system, in mouse embryonic stem cells, to replace the mouse gene C gamma 1, which encodes the constant region of the heavy chain of IgG1 antibodies, with its human counterpart. The mutation was transmitted through the mouse germ line, and the resulting mutant mice were crossed with mice expressing kappa light chains with a human, instead of a mouse, constant region. Mice homozygous for both mutations produce humanized, kappa-chain-bearing IgG1 antibodies at the same level and efficiency as wild-type mice produce murine IgG1 antibodies. These animals should enable the ex vivo production of humanized, chimeric monoclonal antibodies specific for any antigen to which the mouse can respond. CONCLUSIONS: Cre-loxP-mediated gene replacement is a simple and efficient general method of targeted mutagenesis in the mouse.

Animals↗
PubMed1994

IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF-beta and IL-4, and is inhibited by IFN-gamma.

Dense CD4+ T cells isolated from naive mice produce only trace amounts of IL-9 when stimulated by immobilized anti-CD3 in combination with anti-CD28 Abs. In this situation, IL-9 production is significantly stimulated by TGF-beta and further enhanced by the addition of IL-4, which, by itself, has only a minimal influence. IFN-gamma was found to inhibit the enhancing effect of IL-4. However, increasing amounts of IL-4 in the presence of a constant concentration of IFN-gamma could overcome the inhibitory activity of IFN-gamma. The application of CD4+ T cells isolated from IL-2 knockout mice unequivocally revealed that IL-2 is essential for the production of IL-9 by T cells. In addition, the use of T cells from IL-4 knockout mice elucidated that the basic (IL-2 + TGF-beta) mediated IL-9 production is independent of IL-4. Therefore, our results demonstrate that optimal IL-9 production of naive dense CD4+ T cells is positively regulated at different levels: 1) by IL-2, which is essential for IL-9 secretion; 2) followed by TGF-beta, which promotes a considerable increase in IL-9 production above the level induced by IL-2; and 3) finally, by IL-4, which requires the presence of IL-2 and TGF-beta to strongly enhance the production of IL-9. IFN-gamma inhibits the production of IL-9 mainly at the level of IL-4 by neutralizing the effect of this cytokine.

Animals↗
PubMed1994

Modulation of fast excitatory synaptic transmission by cyclothiazide and GYKI 52466 in the rat hippocampus.

The effects of cyclothiazide, a drug which potentiates AMPA receptor-mediated responses and GYKI 52466, a non-competitive AMPA receptor antagonist, were studied on fast glutamatergic transmission in rat hippocampal slices. Cyclothiazide prolonged the decay of AMPA receptor-mediated EPSCs (AMPA-EPSCs) in a concentration-dependent manner. GYKI 52466 reduced the peak amplitude of AMPA-EPSCs and blocked the induction of LTP. When GYKI 52466 was applied in the presence of cyclothiazide it still reduced the peak amplitude of AMPA-EPSCs but was not able to reverse the cyclothiazide induced prolongation of AMPA-EPSC duration. These data suggest that GYKI 52466 and cyclothiazide probably mediate their effects on the AMPA receptor via different binding sites.

2-Amino-5-phosphonovalerate↗
PubMed1994

Analysis of the B-cell progenitor compartment at the level of single cells.

BACKGROUND: During B-cell development in the mouse, the VH, DH and JH elements of the immunoglobulin heavy chain (IgH) locus are rearranged, firstly by DH-JH joining, and then by VH-DHJH joining. In-frame ('productive') VHDHJH joints and DHJH joints in reading frame 2 (one of the three possible DH reading frames) allow the expression of mu and truncated mu chains (D mu proteins), respectively. The expression of such molecules from one of the two IgH loci of a cell is thought to interfere with VH-DHJH recombination on the other IgH locus, and to guide the cells through further development. RESULTS: We have developed a gene amplification assay that permits the examination of rearranged immunoglobulin genes in single cells. Using this assay, we monitored cells bearing DHJH and/or VHDHJH joints at early stages of development: in CD43+ B-cell progenitors, subdivided into fractions A, B, C and C' by flow cytometry, and in CD43- pre-B cells (fraction D). Fraction C was enriched for cells with two non-productive VHDHJH joints. Cells containing both a DHJH joint in DH reading frame 2 and a VHDHJH joint were not seen in any fraction. All fraction D cells harbored an in-frame VHDHJH joint. Cells with two productive VHDHJH joints appear to be selected against throughout development. CONCLUSIONS: Cells expressing D mu proteins appear to be arrested in development as a result of inhibited VH-DHJH joining. Expression of the mu chain is required for maturation into CD43- pre-B cells; accordingly, cells carrying two non-productive VHDHJH joints accumulate in the CD43+ compartment. Such a developmental arrest may also affect cells that express self-reactive VHDHJH antibody domains. Our results indicate further that allelic exclusion at the IgH locus is already established at the pre-B cell stage.

Animals↗
PubMed1994

Nuclear transformation of Volvox carteri.

Stable nuclear transformation of Volvox carteri was achieved using the cloned V. carteri nitA+ gene (which encodes nitrate reductase) to complement a nitA- mutation. Following bombardment of mutant cells with plasmid-coated gold particles, putative transformants able to utilize nitrate as a nitrogen source were recovered with an efficiency of approximately 2.5 x 10(5). DNA analysis indicated that the plasmid integrated into the genome, often in multiple copies, at sites other than the nitA locus. Cotransformants were recovered with a frequency of 40-80% when cells were cobombarded with a selected and an unselected marker. Thus, V. carteri becomes one of the simplest multicellular organisms that is accessible to detailed molecular studies of genes regulating cellular differentiation and morphogenesis.

Blotting, Southern↗
PubMed1994

Investigation of specific binding of antifluorescyl antibody and Fab to fluorescein lipids in Langmuir-Blodgett deposited films using quartz crystal microbalance methodology.

Antifluorescyl IgG antibody and Fab binding to two fluorescein-conjugated lipids was measured using the quartz crystal microbalance methodology. By use of the Langmuir-Blodgett technique, the fluorescein lipids, which were diluted to 5% in a L-alpha-dipalmitoyl phosphatidylethanolamine (DPPE) matrix, were deposited directly onto one gold electrode of the quartz crystal. Binding to films containing the fluorescein hapten was significantly enhanced compared to films of the pure DPPE matrix lipid, indicating that binding occurred primarily through a specific interaction. Association constants were 40-300 times less than for binding to haptens free in solution. Binding of IgG to the lipid in which the hydrocarbon chains and the fluorescein hapten were linked via a hydrophilic spacer was approximately 7 times as great as to the lipid containing no spacer. IgG binding to the lipid containing the spacer was increased 1.5-4.4 times compared to Fab binding for the same lipid. Equilibrium binding curves and kinetic measurements are analyzed quantitatively and compared.

Animals↗
PubMed1994

Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not dependent on IL-4 from non-Th cells.

Interleukin 4 (IL-4) is essential for the induction of immunoglobulin E (IgE) responses in mice. Recent in vitro studies have suggested that IL-4 derived from non T helper (Th) cells, in particular from mast cells and basophils, may be essential for triggering of IL-4 expression in Th cells and may directly contribute to IgE isotype switch induction. Here, we have generated mice carrying a functional IL-4 gene only in Th cells or non-Th cells, respectively, by reconstitution of IL-4-deficient mice (IL-4T mice) with CD4+ or CD4- spleen cells from congenic wild-type animals. In mice in which only CD4+ cells are able to express IL-4, antigen-specific IgE is produced in a T cell-dependent immune response. Thus, induction of IL-4 expression in Th cells can occur in the absence of IL-4 from non-Th cells, which suggests that at least some Th cells can express IL-4 in response to another signal which has yet to be identified. No IgE is detectable, however, in mice in which only CD4- cells can express IL-4, suggesting that Th cells are the primary, if not the only source of IL-4 for initial induction of IgE synthesis.

Animals↗