Search PubMed⌕ Search

Biomedical subjects

G Baumann

Publications and source records attributed to G Baumann.

At least 199 records · Page 11Linked to original sources
PubMed1995

[Differentiation of arousal in sleep before and after CPAP therapy in patients with pronounced sleep apnea syndrome].

The sleep apnea syndrome is often associated with the syndromes of daytime exhaustion and involuntary daytime sleeping fits. The cause is assumed to be fragmentary sleep resulting from night-time arousal. The central nervous activation reactions caused by apnea or hypopnea, respectively, and not the movement arousal determine the sleep structure. We have examined 10 male patients in the age range 40-55 years (48 +/- 6 SD) before and during the first 3 nights of CPAP therapy. Cardiorespiratory polysomnography was performed in all four nights. Sleep way analyzed visually and differentiation was made between respiratory (RA) and movement arousal (MA). All 10 patients had a pronounced sleep apnea syndrome. Deep and dream sleep were reduced, significantly more respiratory arousals occurred than movement arousals. The SWS latency was shortened in the first therapy night, the deep and dream sleep proportions increased and the RA decreased significantly. No further significant changes in the sleep parameters occurred during the second and third nights. We found that the number of apnea/hypopnea was not equal to the number of RA. When less arousal was recognized it was suggestive of a deficit of the diversion function while more RA was indicative of additional respiratory events, e.g. pharyngeal obstructions and hyperventilations which were not recognized as apnea or hypopnea. In addition to its role in the differential diagnosis of sleeping disorders, in particular sleep apnea, arousal differentiation is also an important criterion for estimating the efficiency of CPAP therapy.

Adult↗
PubMed1995

[Obstructive snoring--diagnosis and therapy].

Obstructive snoring belongs to the sleep-related breathing disorders. The characteristics of this disorder is described, following the case report about two young snorers, complaining of excessive day-time sleepiness, involuntary falling asleep in monotoneous situations. Ambulatory monitoring using the four-channel system MESAM-IV showed a Respiratory Disturbance Index of < 5 during a predominantly continuous snoring episode without significant drops in oxygen saturation. Clinical cardio-respiratoric polysomnographic monitoring showed a normal architecture of sleep interrupted by respiratory arousals. Under nasal CPAP treatment these arousals, as well as the complained excessive daytime sleepiness disappeared. The latter fact becomes evident, when comparing the sleep latencies before therapy to those under CPAP-treatment, estimated by the Multiple Sleep Latency Test (MSLT). Thus, this therapy proved to be very effective in patients suffering from obstructive snoring.

Adult↗
PubMed1995

Characteristics of the somatotropic axis in insulin dependent diabetes mellitus.

Growth hormone (GH) plays an important role in glucose homeostasis in both healthy subjects and patients with diabetes. Patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) have high basal and integrated serum GH concentrations, as well as an enhanced GH response to several secretagogues. Yet, these patients have impaired generation of insulin-like growth factor-I (IGF-I). These abnormalities tend to return to normal as an adequate metabolic control is achieved. In view of this hormonal profile, IDDM has been considered a state of relative GH resistance. Studies in experimental animals with streptozotocin-induced diabetes have shown a decreased binding of radiolabeled GH to liver membranes. More recently, adults and children with IDDM have been found to have low levels of the high affinity growth hormone binding protein (GHBP), which represents the extracellular portion of the GH receptor, and is thought to reflect GH receptor tissue concentrations. The abnormalities in the GH/IGF-I axis have been implicated in the worsening of metabolic control that occurs in some patients, as well as in the development of microvascular complications, particularly retinopathy.

Adult↗
PubMed1994

The beta D-sheet residues of the Lck-derived SH2 domain determine specificity of the interaction with tyrosine-phosphorylated ligands in Ramos B cells.

Src homology 2 (SH2) domains are noncatalytic regions that are conserved among a group of cellular signaling proteins. SH2 domains share the common property of binding phosphotyrosine-containing peptides. Previously, we showed that SH2 domains expressed as recombinant glutathione S-transferase-fusion proteins (GST-SH2) from GTPase-activating protein, Shc, zeta-chain-associated protein tyrosine kinase Zap-70, and Src-like tyrosine kinases precipitated distinct sets of phospho-proteins from activated B cells. To determine the intrinsic structural motifs responsible for the binding specificity within the different SH2 domains, we created chimeric SH2 domains especially focusing on crystal structure-defined contact residues. Recombinant SH2 domains of Lck, Zap-70, and Shc were tested in Ramos B cell lysates for phosphotyrosine-dependent protein binding. Biomolecular interaction analysis (BIAcore) was used to characterize the interaction between the various recombinant SH2 molecules and defined phosphorylated peptides. In agreement with the crystal structure data from the Src and the Lck SH2 domains, our results show that most of the "specificity information" of the Lck SH2 domain is provided by the beta D-sheet, located downstream of the SH2 conserved consensus motif GTFLVRES. In addition, the overall affinity is critically influenced by residues located at the N terminus of the SH2 domain.

Amino Acid Sequence↗
PubMed1994

A transcription factor with AP3-like binding specificity mediates gene regulation after an allergic triggering with IgE and Ag in mouse mast cells.

Mast cells are an important source of a number of lymphokines and chemokines primarily those released after challenge with the allergic trigger IgE and Ag. However, the mechanisms of lymphokine and chemokine gene activation in this cell type, as opposed to the mechanisms of activation in T cells, are poorly understood. As a model system, we addressed this issue in mast cells by using the recently cloned chemokine MARC gene, which belongs to the RANTES/sis gene family. After allergic stimulation, MARC induction is pronounced and mast cell specific. Northern blot analysis, in combination with two inhibitors, actinomycin D and cycloheximide, resulted in the formation of our initial hypothesis, which was that both transcriptional and post-transcriptional regulation are involved after stimulation through the Fc epsilon R. We performed a detailed promoter analysis of the cloned MARC gene by using transient assays of transfected reporter gene constructs. Thereby, two potential promoter regions were identified as being crucial for transcriptional stimulation. Additional fine mapping of the proximal element and subsequent electrophoretic mobility shift assays, combined with competitions of known transcription factor binding sites, identified one of the transcription factors in stimulated mast cells as an AP3 or AP3-like binding activity.

Amino Acid Sequence↗
PubMed1994

In vitro characterization of major ligands for Src homology 2 domains derived from protein tyrosine kinases, from the adaptor protein SHC and from GTPase-activating protein in Ramos B cells.

Antigen receptors of B lymphocytes transmit their activation signal to the cell interior by associating with and activation of specific non-receptor tyrosine kinases. Most of these kinases as well as other cytoplasmic effectors contain at least one Src homology 2 (SH2) domain, known to bind tyrosine-phosphorylated proteins. We examined the binding specificity of SH2 domains from different signaling molecules in B cells and found that each of the SH2 domains tested bound distinct subsets of stimulation-dependent phosphoproteins in vitro. SH2 domains from Src-like tyrosine kinases bound predominantly to the HS1 phosphoprotein. The tandem SH2 domains of the ZAP-70 tyrosine kinase bound to phosphorylated Ig-beta but only weakly to Ig-alpha. Also the SHC-derived SH2 domain formed complexes with the tyrosine-phosphorylated Ig-alpha/beta heterodimer, while the C- and N-terminal SH2 domains of GTPase-activating protein displayed completely different binding preferences. These results suggest that cytoplasmic effector molecules can be recruited to the activated B cell receptor in an SH2-phosphotyrosine-mediated manner. The data also provide a possible explanation for the notion that Ig-alpha and Ig-beta might couple to different biochemical pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Left and right heart Doppler stress echo in congestive heart failure.

Doppler echocardiographic assessment of the left and right ventricular function at rest, during and 6 minutes after submaximal exercise was performed in 60 patients with a mean age of 43 +/- 11 years suffering from heart failure classified stage I-III according to the NYHA-criteria and 10 volunteers with a mean age of 36 +/- 9 years who served as a control group. At mitral (m) and tricuspid (t) valve early diastolic peak-flow velocity (VEm, VEt), atrial peak-flow velocity (VAm, VAt), speed-time integrals (Em, Et, Am, At) and the ratios (VE/VAm, VE/VAt, E/Am, E/At) were determined. The left ventricular end-diastolic diameter (LVEDD) and the right ventricular outflow tract (RVOT) were measured in addition. The left ventricular ejection fraction (LVEF) was decreased to < 36% in 9 patients (group 1). In 51 individuals LVEF was found to be > 35% but < 50% or LVEF was shown to be > 50% but VE/VAm-ratio was found to be < 1 (group 2). Out of all the determined parameters, VE/VAt, VEt and VAm during exercise were found to be the most sensitive parameters for the detection of early to advanced grade left heart failure.

Adult↗
PubMed1994

Digital image analysis of self-similar cell profiles.

Many biological objects appear to have self-similar structures which can be characterized by their fractal dimension D. However, applications of the concept of fractal geometry are rather scarce in cell and tissue biology. Here we adapt and analyse critically 3 methods of digital image analysis to measure D of cellular profiles. As prototype examples we investigate in detail 2 samples of cells: (i) human T-lymphocytes from normal donors, and (ii) hairy leukemic cells. It is shown that D correlates to the structural complexity of the individual cell contour. The calculated D values for cells out of the same cell line scatter around a mean value D = 1.15 for T-lymphocytes (S.D. = 0.03) and D = 1.34 for hairy leukemic cells (S.D. = 0.04). Consequently, we interprete D as a statistical measure for the sample's fractal dimension.

Flow Cytometry↗
PubMed1994

Heterogeneity of circulating growth hormone.

Human growth hormone (GH) represents a family of related proteins arising from two genes, alternative mRNA splicing, and several post-translational modifications. In addition, post-secretory events occur when GH enters the circulation. The full scale of GH heterogeneity is only beginning to be appreciated, and new GH forms or related proteins may be discovered in the future. GH measurements are affected by GH heterogeneity. Immunoassays are influenced by the mixture of GH variants, but are not sensitive to GH binding proteins (GHBPs). In contrast, radioreceptor assays are sensitive to both GH variant mixtures and to the high affinity GHBP. It is hoped that in the future, these problems can be minimized by rigorous characterization of existing antibodies with respect to epitope recognition on various GH forms, and ultimately, by production of GH variant-specific antibodies that permit direct and individual assessment of the circulating members of the GH family.

Alternative Splicing↗
PubMed1994

E-selectin polymorphism and atherosclerosis: an association study.

Adhesion molecules like the members of the selectin family participate in the interaction between leukocytes and the endothelium. They are also involved in the pathogenesis of atherosclerotic processes. To contribute to the analysis of the genetic background of atherosclerosis we searched for DNA polymorphisms in the genes encoding adhesion molecules especially E-selectin which seems to be expressed only in activated endothelium. An adenine to cytosine substitution for cDNA position 561 resulting in an amino acid exchange from serine to arginine (position 128) was detected in the epidermal growth factor like domain. A significantly higher mutation frequency (P = 0.02) was observed in 97 patients aged 50 years or less with angiographically proven severe atherosclerosis (allele frequency of arginine 0.155) compared with an unselected population (allele frequency of arginine 0.088) as well as in 40 patients aged 40 years or less (allele frequency of arginine 0.21, P = 0.0025). These data suggest that the 128-serine/arginine polymorphism is associated with a higher risk for early severe atherosclerosis.

Adult↗
PubMed1994

IL-2 promoter-driven lacZ expression as a monitoring tool for IL-2 expression in primary T cells of transgenic mice.

A transgenic mouse system has been established to follow the pattern of IL-2 expression at the level of single T cells. This was achieved by introducing a human IL-2 promoter-driven reporter gene (Escherichia coli lacZ) into the germline of mice and monitoring its product, beta-galactosidase (beta-gal), by FACS analysis. Ex vivo experiments confirmed that the regulated expression of the transgene is comparable with that of the endogenous IL-2 gene. Transgene expression is inducible by mitogens, restricted to T cells, and diminished by immunosuppressive agents, such as cyclosporin A, at concentrations known to suppress IL-2 transcription. Depending on the mitogens used, 30-50% of peripheral T cells produced IL-2 with an asynchronous induction pattern, as measured by transgenic beta-gal activity. Both helper (CD4+CD8-) and cytotoxic T cells (CD4-CD8+) respond with comparable heterogenous expression levels but they show different frequencies of beta-gal production. Transgenic beta-gal-producing T cells were detectable as early as 2 h after mitogen stimulation. These cells represent a transitional IL-2 secreting, IL-2 receptor alpha-chain negative T cell population, which occurs in the autocrine process of T cell activation. Administration of staphylococcal enterotoxin A (SEA), a bacterial superantigen, resulted in a T cell specific (Thy-1.2) increase (2.5-fold) of reporter gene expression in vivo. In summary, we could demonstrate that IL-2 promoter-driven reporter gene expression in transgenic mice is a sensitive tool to characterize IL-2 expressing cells phenotypically.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Long-term efficacy and safety of pimobendan in moderate heart failure. A double-blind parallel 6-month comparison with enalapril. The Pimobendan-Enalapril Study Group.

In view of growing scepticism as to the efficacy and safety of agents with predominant phosphodiesterase inhibiting properties in heart failure, the clinical efficacy and safety of pimobendan, a calcium-sensitizing and partially phosphodiesterase-inhibiting compound, was compared with enalapril in 242 patients with mild to moderate heart failure (NYHA classification II-III) despite diuretics and digitalis, and abnormal haemodynamics at baseline. Patients were randomly assigned to either pimobendan (average 10.3 mg.day-1, n = 119), or enalapril (average 10.7 mg.day-1, n = 123) in a double-blind fashion for 6 months. Forty-two pimobendan and 37 enalapril patients stopped the treatment, five pimobendan and six enalapril due to worsening of failure without death, whereas 13 and eight patients, respectively, died from cardiac disorders (ns). Other reasons for discontinuation and adverse events not leading to discontinuation were also comparable. Although Holter analysis at 14 days, but not at 6 months, indicated increased ventricular extrasystoles in pimobendan patients, these did not lead to serious clinical events. NYHA classification improved similarly in both groups, from 2.51 to 2.16 (pimobendan) and from 2.40 to 2.06 (enalapril). The number of patients needing a change in background therapy or hospitalization did not differ between the two groups. Haemodynamic variables at rest were improved by both compounds after 6 months. In contrast, only enalapril improved haemodynamics during exercise, and reduced the cardiothoracic ratio. The primary endpoint, exercise capacity, increased significantly during the first 3 months by 45 and 53 s, under pimobendan and enalapril, respectively, but, although unchanged thereafter, the improvement was no longer statistically significant at 6 months in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗
PubMed1994

Quantitative polymerase chain reaction (PCR) to analyze messenger-RNA expression in tissue obtained by directional atherectomy.

There is a widely recognized need to evaluate gene expression in human vascular plaque tissue. Directional atherectomy made it possible to sample plaque tissue from primary stenoses and subsequently from restenoses from one individual. Conventional approaches to analyze mRNA content of lesions, such as Northern blot analysis, and slot blot analysis are not sensitive enough to evaluate mRNA levels in atherectomy specimens limited by low cell number or low copy number per cell. The purpose of this study was to investigate whether gene expression, as reflected in mRNA copy number, in atherectomy biopsies, could be sufficiently analyzed by quantitative polymerase chain reaction (PCR). The authors applied PCR to detect platelet-derived growth factor-A mRNA expression in 12 human lesions sampled percutaneously by directional atherectomy. After reverse transcription, specific amplification of the resulting cDNA was performed. This was successful with cDNA from less than 0.5 microgram of total cellular RNA. To quantitate mRNA content of specimens, the authors coamplified cDNA copies of mRNA from lesions and from a synthetic reference RNA in the same reaction vessel. Quantitative PCR is best applied if tissue is more than 45 mg in weight and of high cellularity with low calcification. This method allows quantitation of mRNA in human primary and restenotic lesions, and it complements histochemical approaches and in situ hybridization of coronary and peripheral atherectomy specimens.

Aorta↗
PubMed1994

Distribution of growth hormone receptor messenger ribonucleic acid containing and lacking exon 3 in human tissues.

The extent of expression of the GH receptor (GHR) in human tissues is largely unknown. In some cell lines and placenta, the GHR gene generates two different mRNAs by alternative splicing of exon 3, one coding for a full-length receptor (GHR + 3) and the other for a receptor isoform that lacks exon 3 (GHR-3), with deletion of amino acid residues 7-28. To determine the distribution of the GHR and the relative abundance of its two isoforms in man, we studied a variety of tissues obtained at autopsy by reverse transcription and polymerase chain reaction (PCR) amplification, using isoform-specific primers. The nature of the PCR products was verified by restriction analysis and DNA sequencing. The relative proportions of the two GHR isoforms were determined by competitive PCR using a 32P-labeled anti-sense primer and a mixture of both isoform-specific sense primers in equimolar amounts. Electrophoretic bands corresponding to the amplification products were excised and counted, or quantitated by laser densitometry. Restriction analysis and sequencing of the amplified products were consistent with their predicted sequence. Both GHR transcripts were found in all 19 tissues tested, but their relative proportions varied depending on the tissue and, to a lesser extent, between subjects. They ranged from a preponderance of GHR-3 (kidney, bladder, adrenal, and brain stem) to a predominance of GHR + 3 (skeletal muscle and liver). We conclude that the GHR gene is widely expressed in human tissues. Both GHR + 3 and GHR-3 transcripts are present, but their relative proportions depend on the tissue and, possibly, the metabolic status. The physiological significance of the existence of two human GHR forms remains to be elucidated.

Base Sequence↗
PubMed1994

The stoichiometry of growth hormone-binding protein complexes in human plasma: comparison with cell surface receptors.

The recent demonstration of two independent receptor-binding sites (sites 1 and 2) on human GH (hGH) raises the question of the stoichiometry of circulating GH-binding protein (GH-BP) complexes in human plasma (i.e. is it one hGH per one GHBP or one hGH per two GHBPs?). Previous studies have all assumed 1:1 binding in plasma, based on gel exclusion chromatography and cross-linking data. To address this issue, human plasma was incubated with radioiodinated hGH as well as hGH mutants that had either a Tyr103-->Ala or a Gly120-->Arg substitution in the region of binding site 2. The former mutant retains normal site 2 binding activity even when iodinated; the latter has binding site 2 inactivated. Bound and free hGH were then separated on a Sephadex G-100 column according to a standard protocol for measuring GHBP. In all three cases, more than 90% of the high affinity GH-BP complex eluting from the column was consistent with 1:1 binding. Similar results were obtained when a physiological amount of recombinant or purified natural GHBP was substituted for plasma. However, at supraphysiological concentrations of GHBP, an additional component corresponding to the 2:1 complex eluted from the column; the relative proportions of the 2:1 and 1:1 complexes were dependent on the GHBP concentration. These data suggest that at physiological GHBP levels in plasma, the 1:1 complex predominates, and that small amounts of the 2:1 complex may be difficult to detect because of partial peak overlap with the 1:1 complex, dissociation, and, in whole plasma, coelution with the low affinity GHBP complex. Calculation of the theoretical partition of hGH between 1:1 and 2:1 complexes indicated that at concentrations of GHBP prevailing in plasma (approximately 1 nmol/L), the 1:1 complex predominates, but that at the high receptor concentrations prevailing at the cell surface (60 nmol/L to 6.7 mumol/L, depending on the cell type), virtually all hGH is captured in a 2:1 complex. These findings are consistent with the present and previous experimental data on the size of the circulating high affinity GH-BP complex, as well as with those indicating the importance of GH-induced receptor dimerization for GH action. A functional consequence of the large concentration difference between GHBP in plasma and GH receptors at the cell surface is that the circulating GHBP can serve as a dynamic buffer, modulating bound and free GH and prolonging its half-life, whereas the receptor acts as a dominant force in unidirectional capture of GH.(ABSTRACT TRUNCATED AT 400 WORDS)

Carrier Proteins↗