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Biomedical subjects

S Müller

Publications and source records attributed to S Müller.

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

Different internal metabolites trigger the induction of glycolytic gene expression in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the sugar-induced expression of various genes coding for glycolytic enzymes is triggered by increases in the concentrations of different internal metabolites. Here, we show that the induction of the glycolytic isoenzyme enolase 2 is strictly dependent on the abilities of different mutant strains to increase the level of glucose-6-phosphate after the addition of sugars. In contrast, the induction of alcohol dehydrogenase I is dependent on increasing concentrations of metabolites in the late stages of glycolysis.

Alcohol Dehydrogenase↗
PubMed1995

Intestinal cytomegalovirus disease in immunocompromised patients may be ruled out by search for cytomegalovirus DNA in stool samples.

Cytomegalovirus (CMV) PCR from stool specimens was adopted as a diagnostic tool for patients with suspected CMV colitis. After being established, the method was evaluated in 17 AIDS patients and 19 other immunocompromised patients by comparison of PCR results with clinical, histological, and microbiological or virological data. CMV PCR was positive in 4 symptomatic patients with proven CMV colitis and negative in 15 of 16 patients without characteristic histopathology. Neither CMV immunoglobulin G seropositivity nor intestinal symptoms alone were significantly associated with positive PCR results, but severe active systemic CMV infection may lead to a positive PCR. Absence of CMV DNA in stool samples may prove useful in ruling out CMV related colitis.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Soluble interleukin-4 receptor in atopic children.

The levels of natural soluble interleukin-4 receptor (shuIL-4R) were determined in the peripheral blood of 29 children with stable asthma, 10 children with asthma and acute respiratory infection, 11 healthy children with acute airway infection and 31 healthy controls. Healthy controls revealed the highest levels (median 1,082 pg/ml, range 524-1,900 pg/ml); which differed significantly from levels obtained with the blood of stable asthmatics (p < 0.01, median 658 pg/ml, range 329-1288 pg/ml), patients with asthma and acute respiratory infection (p < 0.01, median 663 pg/ml, range 0-1,250 pg/ml) and patients with respiratory infection alone (p < 0.01, median 674 pg/ml, range 466-1,110 pg/ml). In contrast, there was no significant difference in shuIL-4R content of cord blood obtained from newborns with a high or low risk of atopy. Additional analysis of interleukin-4 receptor (huIL-4R) on cultured lymphocytes from 13 stable asthmatic children and 14 healthy children indicated higher expression on CD4 cells (p < 0.05, median 2.2%, range 0.8-7.8%) compared to healthy controls (median 1.3%, range 0.7-3.3%). Therefore, diminished shuIL-4R concentrations in plasma may be related to inflammatory states but not specifically to atopy. The results support the notion that huIL-4R expressed on the cell surface may be regulated differently from the soluble form.

Acute Disease↗
PubMed1995

Identification of an idiotypic peptide recognized by autoantibodies in human immunodeficiency virus-1-infected individuals.

Antibodies against HIV-1 proteins in HIV-1-infected individuals share a cross-reactive idiotype defined by the monoclonal antiidiotypic antibody 1F7 (5). Using a computer algorithm based on the molecular recognition theory, regions of inverse hydropathy between the variable sequence of 1F7 and human monoclonal anti-HIV-1 antibodies were identified, which are assumed to be involved in idiotype-antiidiotype contacts. A peptide was designed from the proposed contact in the variable heavy chain framework 3-complementarity determining region 3 (FR3-CDR3) of human antibodies and was synthesized. This peptide is recognized by the antiidiotype 1F7 and inhibits the binding of 1F7 to human anti-HIV-1 antibodies which express the 1F7 idiotype. A survey of normal and HIV-1-infected sera revealed the presence of antibodies in infected sera which bind to the FR3-CDR3 peptide. The biological relevance of autoantibodies against a self idiotope associated with HIV-1 infection is discussed in the context of the regulation of the antibody response to HIV-1.

Algorithms↗
PubMed1995

Corrected transposition of the great arteries: dynamic three-dimensional echocardiography and volumetry. A new diagnostic tool in intensive care management.

Today, an increasing incidence of severe complications of cardiac malformations in adult patients must be expected since the life expectancy of such individuals is prolonged due to improved management. A 32-year-old woman with corrected transposition of the great arteries (CTGA) was admitted to the intensive care unit because of cardiac decompensation. Information provided by multiplane two-dimensional transesophageal echocardiography was not sufficient for an unequivocal explanation of the cardiac decompensation. In CTGA uncommon complications may cause pulmonary edema. Using dynamic three-dimensional echocardiography to reveal function, volume parameters and the morphology of both ventricles and to exclude additional complications may be considered an adequate diagnostic tool for responding to this challenge.

Adult↗
PubMed1995

[Retrograde intravenous perfusion as ultima ratio in potential amputation patients with peripheral arterial occlusive disease].

In 21 patients with critical ischemia and/or inflammation of the leg facing possible amputation, retrograde intravenous perfusion (RVP) was used to administer fibrinolytics, vasodilators and antibiotics. Amputation was avoided in 15 patients. In 4 patients, RVP was interrupted due to unsuitable veins for putting in cannulas. After introducing a 3-in-1-Block (Winnie) for analgesia, 7 courses of treatment at least were reached before unbearable pain became a reason for stopping therapy. RVP should, therefore, be considered as the last resort in the treatment of critical ischemia and/or inflammation of the leg of patients facing possible amputation.

Aged↗
PubMed1995

[Uptake of DL-3-123I-iodo-alpha-methyltyrosine in recurrent brain tumors].

DL-3-123I-iodo-alpha-methyltyrosine (123I-IMT) is a radiopharmacon which concentrates in brain tumors and can be employed in SPECT. We performed 20 studies in 16 patients after neurosurgery for malignant brain tumors (localization of the primary tumor by CT/MRI). Tumor/non-tumor ratios (T/NT) were calculated in ROI-technique. In 17 cases there was a recurrence or tumor remnant. 14/17 were detectable by increased uptake (T/NT 1.43-2.25). The scans were correlated with CT/MRI studies and validated by biopsy (6/14) or follow-up. All 3 patients without recurrence (neuroradiological follow-up over 6-24 months) had a negative scan. 123I-IMT scintigraphy provides complementary information to CT and MRI. In equivocal neuroradiological or clinical cases it may be valuable in the detection of tumor recurrences and allows an earlier onset of therapy.

Astrocytoma↗
PubMed1995

[The Mannheim long-term study of schizophrenia. Initial results of follow-up of the illness over 14 years after initial inpatient treatment].

A 14-year follow-up was accomplished on 56 out of a total of 70 patients first admitted to hospital with Schneiderian first-rank symptoms. Data collected during 5 years after index admission were also at our disposal. Three quarters of the probands are living alone, and barely one third are in regular employment. At the time of the 14-year follow-up about one third showed delusions or hallucinations. Almost the same number had psychological impairments and 64% were socially disabled. Comparison with the data collected at 1 year and 5 years reveals no difference in the rates of impairments and symptomatology, but a significant increase of social disability.

Adult↗
PubMed1995

[Segregation of pigment cell anomalies in Munich miniature swine (MMS) Troll crossed with German Landrace].

In order to study the inheritance of melanocytic lesions in the Munich Miniature Swine (MMS) Troll, we established the F1-, F2- and R1-generations, starting with one melanoma-bearing MMS-Troll boar and four German Landrace sows as founder animals. A total of 168 animals were born, 24 in the F1-, 111 in the F2-, 19 in the B1DL-, and 14 in the B1Troll-generation. Benign lesions with lentigoid melanocytic hyperplasia or nests of hyperplastic melanocytes like in human junctional nevus were seen in 10 (41.7%) F1-, 17 (15.3%) F2-, 2 (10.5%) B1DL-, and 6 B1Troll-animals. Malignant melanomas occurred only in the F2-(4 animals; 3.6%) and in the B1Troll-(1 animal; 7.1%) generation. The observed segreation suggests different modes of inheritance for nevi and melanomas. The segregation of nevi can be explained by a major gene model with additional modification by a polygenic component. For melanoma, a major gene model does not fit the data sufficiently. Therefore, a two-or-three-locus model with doubled or tripled recessive affected animals has to be supposed for the inheritance of melanoma. Influence of SLA-haplotypes could not be observed.

Animals↗
PubMed1994

Complete DNA sequence of yeast chromosome II.

In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity.

Base Composition↗
PubMed1994

Interaction of tryptophan residues of cytochrome P450scc with a highly specific fluorescence quencher, a substrate analogue, compared to acrylamide and iodide.

The cytochrome P450scc tryptophan fluorescence was studied by the use of the three quenchers acrylamide, 25-doxyl-27-nor-cholesterol (CNO) and potassium iodide (KI). All the nine tryptophan residues were accessible to acrylamide. Whereas a strong interaction (static quenching) between acrylamide and tryptophan in the active site had been found previously for cytochrome P450c21 [Narasimhulu, S. (1988) Biochemistry 27, 1147-1153], in the case of P450scc the temperature dependence of the slope of the linear Stern-Volmer plots indicated a dynamic quenching mechanism. This mechanism was confirmed by fluorescence lifetime measurements. Of the three observed life-times tau 1 = 3.1 +/- 0.5 ns, tau 2 = 0.7 +/- 0.25 ns and tau 3 = 20 +/- 10 ps, tau 1 decreased noticeably as a function of the acrylamide concentration. CNO, a spin-labeled substrate which is known to bind tightly to the substrate-binding site of P450scc, quenched 15.5% of the total fluorescence. The Lehrer plot of this compound indicated a static quenching process with a reciprocal quenching constant of 1/Ks = 4 microM, a value which is in accord with the dissociation constant. Our data indicate that CNO quenches selectively one or two tryptophan residue(s) in the active site. The fluorescence spectrum of the residue(s) accessible to CNO was characterized by a red-shifted emission maximum (from 332 nm to 336 nm). The same residue(s) appeared to be quenched by potassium iodide, although much less effectively (1/Ks = 0.12 M). The most probable candidate for a complex formation with CNO is Trp417, which is rather close to Cys422 (the fifth heme ligand). Four arginine residues (Arg411, Arg420, Arg425 and Arg426) in the heme peptide may constitute the iodide-binding site.

Acrylamide↗
PubMed1994

Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci.

Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Cloning of a cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase from rat liver and its regulation by thyroid hormones.

A full-length 2.4-kb cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) was cloned from rat liver using PCR techniques. The cloned gene encodes a protein of 727 amino acids. The calculated molecular mass of 80,898 Da is higher than the apparent molecular mass observed by SDS/PAGE (74,000 Da) of the purified enzyme. This result indicates that the enzyme is synthesized as a precursor with a putative mitochondrial signal sequence. mRNA for this gene was detected in liver, heart, muscle, brain, testes, and pancreas. With the exception of testes, basal expression levels were very low in all tissues examined. However, application of thyroid hormones led to a 10- to 15-fold increase in liver glycerol-3-phosphate dehydrogenase mRNA, whereas hypothyroidism further decreased the mRNA level.

Amino Acid Sequence↗
PubMed1994

Mechanisms of dichotomous action of IL-2-Pseudomonas exotoxin 40 (IL-2-PE40) on cell-mediated and humoral immune response.

IL-2-PE40 is a chimeric protein composed of human IL-2 genetically fused to the amino terminus of a modified form of Pseudomonas exotoxin lacking its cell recognition domain. The immunosuppressive efficacy of IL-2-PE40 was demonstrated in several experimental murine transplant and autoimmune models. However, some observations suggested that IL-2-PE40 could not inhibit the humoral response. In this report, we describe the dichotomous effects of IL-2-PE40 on humoral and cell-mediated immune response in a simple, well characterized in vivo model. Although IL-2-PE40 inhibited the cell-mediated delayed type hypersensitivity reaction to SRBC, it increased the humoral immune response to the same Ag. To understand the mechanism of dichotomous action of IL-2-PE40 on the immune response, IL-2R-bearing T cells were treated with IL-2-PE40 in vitro and the cytokine expression was studied at mRNA and protein level. Similar to IL-2, IL-2-PE40 promoted the expression of T helper 1-like (IFN-gamma) as well as T helper 2-like (IL-4, IL-10) cytokines. These in vitro studies show that IL-2-PE40 can induce signal transduction in activated T cells through the IL-2R before exerting its cytotoxic effect. In contrast to DTH reaction, humoral immune response requires T cell help only for a limited period. Therefore, the short-term stimulation of T helper cells by IL-2-PE40 may be sufficient in vivo to mediate a B cell response in the local environment, whereas the DTH reaction and other cell-mediated immune responses are inhibited by the toxin moiety of the chimeric protein.

Animals↗
PubMed1994

Sp1-mediated transcriptional activation is repressed by Sp3.

Sp1, Sp3 (SPR-2) and Sp4 (SPR-1) are human sequence-specific DNA binding proteins with very similar structural features. In this report, we have analyzed Sp3 in direct comparison with Sp1. We have raised antibodies against both Sp1 and Sp3, and show that Sp3 protein, like Sp1, is expressed in various cell lines. Co-transfection experiments in different mammalian cell lines reveal that in contrast to Sp1 and Sp4, Sp3 is not able to activate several Sp1 responsive promoters. In addition, Sp3 also fails to activate reporter constructs in Drosophila SL2 cells lacking endogenous Sp factors. Instead, we find that Sp3 represses Sp1-mediated activation in a linear dose-dependent manner. A mutant of Sp3 lacking the DNA binding domain does not affect activation by Sp1, suggesting that the inhibition is most likely due to the competition with Sp1 for their common binding sites. To determine if any structurally similar domain of Sp3 is able to replace partially homologous domains of Sp1, we have generated chimeric proteins and tested their activation characteristics in gene transfer experiments. It appears that neither the glutamine-rich domains A and B nor the D domain of Sp1 can be replaced by the homologous regions of Sp3. Our results suggest that Sp3 is an inhibitory member of the Sp family.

Animals↗
PubMed1994

Fusion proteins containing the cytochrome b2 presequence are sorted to the mitochondrial intermembrane space independently of hsp60.

hsp60 is a chaperonin located in the mitochondrial matrix. It has been suggested that hsp60 participates in two processes: protein folding in the matrix, and the sorting of imported proteins to the intermembrane space. We analyzed hsp60 function by allowing isolated mitochondria to import two model precursor proteins and then measuring the binding of these proteins to the chaperonin. Of the methods that we tested for monitoring the association of imported proteins with hsp60, only co-immunoprecipitation with specific anti-hsp60 antibodies proved to be reliable. A chimeric matrix-targeted precursor, consisting of a mitochondrial presequence fused to a chloroplast-encoded protein, bound stably to hsp60 after import. In contrast, there was no detectable binding to hsp60 with a fusion protein that was targeted to the intermembrane space by the bipartite cytochrome b2 presequence. Analysis of a translocation intermediate demonstrated that the cytochrome b2 presequence arrests import through the inner membrane, with the result that the attached passenger protein is never exposed to hsp60.

Biological Transport↗