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B Müller

Publications and source records attributed to B Müller.

At least 289 records · Page 16Linked to original sources
PubMed1992

[Evaluation of TSH suppression using a 3d-generation TSH assay: diagnostic and therapeutic consequences].

UNLABELLED: We measured basal and TRH-stimulated TSH values with a 3rd generation assay in patients under suppressive thyroxine (T4) therapy for thyroid carcinoma or goiter and in patients with overt hyperthyroidism. All hyperthyroid patients had undetectable basal TSH levels (< 0.01 mU/l). In patients on suppressive T4 treatment basal TSH values were undetectable in 37.5% (= group A) and measurable in the intermediate range of 0.01-0.05 mU/l in 62.5% (= group B). After TRH administration there was no TSH increase in the hyperthyroid patients (< 0.01 mU/l in 100%). T4-treated patients of group A showed no relevant TSH stimulation in 58% (peak < or = 0.05 mU/l = total TSH suppression). An increase of > 0.05 mU/l could be measured in 42% of group A and 100% of group B (= subtotal TSH suppression). Many of these TSH values measured by a 3rd generation assay are in the undetectable range for most of the commercially available 2nd generation assays (< 0.10 mU/l). CONCLUSION: TSH assay of the 3rd generation decisively improves the diagnosis of hyperthyroidism and probably also borderline hyperthyroidism. Against the background of increased risk of osteoporosis and cardiac function disorders as a result of suppressive T4 treatment, our results suggest the following practical therapeutic guidelines: total TSH suppression with the risk of iatrogenic hyperthyroidism should be confined to high risk patients (eg with metastatic thyroid cancer). Where the risk is low, however (thyroid cancer with favourable prognosis, goiter, goiter prophylaxis), only subtotal TSH suppression is indicated.

Adult↗
PubMed1992

Template. Phosphorothioate oligonucleotides duplexes as inhibitors of HIV-1 reverse transcriptase.

We have investigated the interaction between a number of 14 mers phosphorothioate oligonucleotides and HIV-1 reverse transcriptase. Two methods were used to measure the affinity of the analogs for the enzyme. In the first, the oligonucleotide or its duplex with Poly(rl) were used as inhibitors of the enzyme using Poly(rA).(dT)14 as template primer. In the second, the oligonucleotides or their duplexes were used to displace a fluorescent template primer complex of known affinity from its binding site on reverse transcriptase. The two methods gave the same relative order of affinity. Phosphorothioate oligodeoxyribonucleotides had a much higher affinity than oligo(dC)14 and it was increased on hybridization. Quantitatively similar results were obtained for S(dC)14 or its analog with bases in the alpha-configuration. Of the analogs tested, only S(dC)14 showed priming activity.

Antiviral Agents↗
PubMed1992

Structure-function relationships of HIV-1 reverse transcriptase determined using monoclonal antibodies.

The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is one of the main targets in approaches to the chemotherapy of AIDS. A detailed knowledge of structure-function relationships of this enzyme is a prerequisite for rational drug design. We have used monoclonal antibodies as tools to identify functionally important regions of the protein. The preparation of 23 murine monoclonal antibodies (mAb) against HIV-1 reverse transcriptase and their different effects on the enzyme are described. The interaction of purified mAbs with HIV-1 RT was demonstrated by enzyme-linked immunosorbent assay (ELISA), Western blots, and high performance liquid chromatography size exclusion chromatography. One of the antibodies also recognized recombinant HIV-2 RT. Antibody binding epitopes on HIV-1 RT were analyzed by immunoblotting using cyanogen bromide fragmented RT, C-terminally truncated mutants, and a peptide ELISA employing 15-mer synthetic overlapping peptides spanning nearly the complete polypeptide chain. The epitopes were mapped within three domains corresponding to amino acids 200-230, 300-428, and 528-560. Two mAbs show neutralizing properties on enzymatic functions of RT. One affects the polymerase activity and to a certain degree the RNase H activity of the enzyme, whereas the other inhibits the latter activity exclusively. mAb 28, which blocks the polymerase activity, interferes with the nucleotide binding region of RT, as shown by fluorescence spectroscopy using a labeled template/primer complex. By investigating the antibody effects on dimer formation of the heterodimeric enzyme, three domains corresponding to amino acids 230-300, 350-428, and residues around amino acid 540 involved in protein-protein interactions were localized.

Antibodies, Monoclonal↗
PubMed1992

ATP-dependent branch migration of Holliday junctions promoted by the RuvA and RuvB proteins of E. coli.

The RuvA and RuvB proteins of E. coli, which are induced as part of the cellular response to DNA damage, act together to promote the branch migration of Holliday junctions. Addition of purified RuvA and RuvB to a RecA-mediated recombination reaction stimulates the rate of strand exchange and the formation of hetero-duplex DNA. Stimulation does not occur via interaction with RecA; instead, RuvA and RuvB act directly upon recombination intermediates (Holliday junctions) made by RecA. We show that RuvAB-mediated branch migration requires ATP and can bypass UV-induced DNA lesions. At high RuvB concentrations, the requirement for RuvA is overcome, indicating that the RuvB ATPase provides the motor force for branch migration. RuvA protein provides specificity by binding to the Holliday junction, thereby reducing the requirement for RuvB by 50-fold. The newly discovered biochemical properties of RuvA, RuvB, and RuvC are incorporated into a model for the postreplicational repair of DNA following UV irradiation.

Adenosine Triphosphate↗
PubMed1992

RNase H activity of HIV reverse transcriptases is confined exclusively to the dimeric forms.

A method for the rapid preparation of a defined substrate to monitor RNase H activity has been developed. Using this substrate, we have investigated the RNase H activities of the different forms of recombinant HIV-1 and HIV-2 reverse transcriptase (RT) in detail. As we report here, RNase H activity is associated only with the dimeric forms (p51/p66 or p66/p66) of the enzymes.

Amino Acid Sequence↗
PubMed1992

Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin-associated protein B29.

Membrane-bound immunoglobulins (Ig) on the surface of murine B cells are noncovalently associated with a heterodimeric protein complex of MB-1 and B29 (also called Ig-alpha and Ig-beta). The Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. We have isolated and sequenced a full-length cDNA clone encoding the human homologue of the B29 protein. The predicted amino acid sequence was compared to its murine counterpart, to MB-1 and to the human T cell receptor (TcR)-associated CD3 proteins. The alignment of the human B29 protein with its murine counterpart revealed 90% homology in the C-terminal portion comprising the cytoplasmic tails, the transmembrane regions and the adjacent 26 amino acids of the extracellular regions. Only 59% homology was found in the rest of the Ig-like extracellular domains. The high degree of conservation observed for the C-terminal amino acids suggested that these domains of the proteins play important functional roles for the Ig complex. Indicative of this was the conservation of the antigen receptor tail motif D-(X)7-E/D-(X)2-Y-(X)2-L-(X)7-Y-(X)2-L/I which is thought to be a component of signal transduction pathways. This motif is also found in the human and murine MB-1 proteins as well as in the TcR-associated CD3 molecules. Further regions of homology between B29, MB-1 and the CD3 proteins included extracellular residues which were predicted to maintain the Ig-like structure, and hydrophilic residues within the transmembrane regions which may be utilized during the intracellular assembly and transport of the oligomeric Ig/MB-1/B29 or TcR/CD3 complexes. Thus the similarities found between B29, MB-1 and the CD3 proteins suggest conserved functions for both the Ig- and TcR-associated proteins.

Amino Acid Sequence↗
PubMed1992

Unusual stability of recombination intermediates made by Escherichia coli RecA protein.

The structure and stability of recombination intermediates made by RecA protein have been investigated following deproteinization. The intermediates consist of two duplex DNA molecules connected by a junction, as visualized by electron microscopy. Although we expected the structures to be highly unstable due to branch migration of the junction, this was not the case. Instead, we found that the intermediates were stable at 37 degrees C. At 56 degrees C, greater than 60% of the intermediates remained after 6 h of incubation. Only at higher temperatures was significant branch migration observed. This unexpected stability suggests that the formation of extensive lengths of heteroduplex DNA in Escherichia coli is likely to require the continued action of proteins, and does not occur via spontaneous branch migration. We show that heteroduplex DNA may be formed in vitro by ATP-dependent strand exchange catalysed by RecA protein or by the RuvA and RuvB proteins of E. coli.

Bacterial Proteins↗
PubMed1992

Iloprost preserves endothelial function against cyclosporin A and sensitises microvessels towards endothelium-dependent and -independent vasodilatation.

The effects of iloprost have been investigated on the endothelial damage produced by cyclosporin-A (Cy-A) and on the microvascular reactivity to sodium nitroprusside (SNP), acetylcholine (ACh) and isoprenaline (ISO) following iloprost treatment i.e. in the absence of effective plasma levels, using the hamster cheek pouch. It has been shown that iloprost protects the microvascular arteriolar endothelium from functional damage by Cy-A and that iloprost infusion for 12-14 hr sensitizes the arterioles to ACh, SNP and ISO, an effect which is evident 5 hr but not 24 hr following treatment and in the case of ACh is abolished by indomethacin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

The radiation dose to surgical personnel during intraoperative radioimmunoscintimetry.

To estimate the radiation exposure to surgical personnel caused by intraoperative radioimmunoscintimetry, we measured dose rates at different distances from patients who had been injected with 950 MBq technetium-99m-labelled intact carcinoembryonic antigen (CEA)-specific antibodies (Szintimun CEA, Behring AG Marburg, FRG) for immunoscintigraphy 24 h earlier. At 0.05 m (corresponding to working positions during surgery) we found 2.0-16.0 microSv h-1 (average 6.4), which is similar to results for nuclear medicine staff. Thus, if radioimmunoscintimetry is to become a routine procedure, according to national regulations in some countries of the European Communities surgical personnel might be regarded as professionally exposed to radiation.

Colorectal Neoplasms↗
PubMed1992

Estimation of the male and female mutation rates in Duchenne muscular dystrophy (DMD).

We present the results of an international collaborative study aimed at estimating the ratio of male to female mutation rates in Duchenne muscular dystrophy based on the method of C. Müller and T. Grimm. With a sample size of 295, this ratio is found to be very close to 1, thus giving evidence for equal mutation rates in males and females in Duchenne muscular dystrophy.

Blotting, Southern↗
PubMed1992

Fragile site (16) (q22). III. Segregation analysis.

The rare autosomal fragile site, fra (16) (q22), is the most common of all rare autosomal fragile sites and has a heterozygote frequency of about 5%. Evidence for it was found following the segregation expected from a simple codominant trait with complete penetrance; this is in contrast to a variety of other rare autosomal fragile sites. Based on the analysis of 12 families in which fra (16) (q22) is segregating, we found that, whereas complete penetrance could be confirmed, the transmitting parent was significantly more likely to be of the female sex. On the other hand, there was no evidence for preferential transmission to offspring of either sex.

Chromosome Fragile Sites↗
PubMed1992

Role of prostanoids in the inflammatory reaction and their therapeutic potential in the skin.

Vasodilatory prostaglandins (PG), contributing to the inflammatory reaction, have gained considerable attention. It is becoming apparent that PG have pharmacological effects traceable to biological activities distinct from smooth muscle relaxation. The data from pharmacological experiments presented here indicate the diverse action of vasodilatory PG analogues in the skin of laboratory animals. Nocloprost, a stable PGE2 analogue, induced erythema in intact skin of rats when applied topically and inhibited in the same dose range an irritant-induced inflammatory reaction in the ears of mice. Iloprost, a stable PGI2 analogue, showed proinflammatory activity after local application by enhancing the leukotriene B4 induced cell infiltration in the skin of mice. The attenuation of the spreading of ear necrosis in mice, on the other hand, indicates an anti-ischemic therapeutic potential of iloprost. Research in the past has elucidated the influence of PG on the vascular component of inflammation, but the role of PG on the cellular component of inflammation is less clear. The diverse effects of PG in skin indicate the need for a better understanding of their local actions.

Animals↗
PubMed1992

Effects of amiodarone versus quinidine and verapamil in patients with chronic atrial fibrillation: results of a comparative study and a 2-year follow-up.

Rapid, reliable and safe reestablishment of sinus rhythm is the major aim of pharmacologic treatment in patients with chronic atrial fibrillation. The mainstay of therapy in this arrhythmia has been quinidine. More recently, amiodarone was shown in non-comparative studies to be superior to class IA agents under certain conditions. In 40 patients with atrial fibrillation persisting for 4 weeks up to 2 years, the efficacy and safety of either quinidine and verapamil (days 1 to 3, quinidine 1,500 mg/day; days 4 to 6, quinidine 1,500 mg + verapamil 240 mg/day) or amiodarone therapy (days 1 to 3, amiodarone 1,200 mg/day intravenously; days 4 to 14, amiodarone 800 mg/day orally) were randomly examined. Responders continued on their effective medication for 3 months. Thereafter, all patients were treated with a fixed regimen of quinidine (480 mg/day) plus verapamil (240 mg/day) for up to 2 years. During atrial fibrillation, quinidine reduced mean ventricular cycle length by 40 ms (-5%), quinidine and verapamil increased mean cycle length by 57 ms (8%) and amiodarone by 192 ms (28%, p less than 0.01). In addition, quinidine and verapamil had a characteristic "rate-smoothing" effect on atrioventricular conduction during atrial fibrillation. The rhythm was converted to sinus rhythm after quinidine in 5 (25%) of 20 patients and after the combination of quinidine and verapamil in 11 (55%) of 20 patients. Amiodarone restored sinus rhythm in 12 (60%) of 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1992

Isolation and characterization of bacteriophages specific for capsular antigens K3, K7, K12, and K13 of Escherichia coli.

Four bacteriophages recognizing the Escherichia coli capsular antigens K3, K7, K12, and K13, respectively, were isolated from pooled sewage samples. The nucleic acid of these phages was identified as double-stranded DNA of different size (phi K3, 71.3; phi K7, 32.8; phi K12, 42.9; phi K13, 43.4 kbp). Three of these phages belonged to Bradley's morphology group C and were specific for K3, K7, and K12 antigens, respectively. The phage phi K13 (Bradley's group A) attacked not only E. coli K13 strains but also E. coli producing the closely related K20 and K23 antigens. It is suggested that the common basic repeating units occurring in these capsular polysaccharides are the primary receptor of phi K13. It could be demonstrated that the four phages were able to depolymerize enzymatically the capsular polysaccharides isolated from the respective host strains.

Antigens, Bacterial↗