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Biomedical subjects

H Bär

Publications and source records attributed to H Bär.

At least 19 recordsLinked to original sources
PubMed2005

Exploring the mechanical behavior of single intermediate filaments.

Intermediate filaments (IFs) are structural elements of eukaryotic cells with distinct mechanical properties. Tissue integrity is severely impaired, in particular in skin and muscle, when IFs are either absent or malfunctioning due to mutations. Our knowledge on the mechanical properties of IFs is mainly based on tensile testing of macroscopic fibers and on the rheology of IF networks. At the single filament level, the only piece of data available is a measure of the persistence length of vimentin IFs. Here, we have employed an atomic force microscopy (AFM) based protocol to directly probe the mechanical properties of single cytoplasmic IFs when adsorbed to a solid support in physiological buffer environment. Three IF types were studied in vitro: recombinant murine desmin, recombinant human keratin K5/K14 and neurofilaments isolated from rat brains, which are composed of the neurofilament triplet proteins NF-L, NF-M and NF-H. Depending on the experimental conditions, the AFM tip was used to laterally displace or to stretch single IFs on the support they had been adsorbed to. Upon applying force, IFs were stretched on average 2.6-fold. The maximum stretching that we encountered was 3.6-fold. A large reduction of the apparent filament diameter was observed concomitantly. The observed mechanical properties therefore suggest that IFs may indeed function as mechanical shock absorbers in vivo.

Animals↗
PubMed2002

[Occlusion of the arteries of the fingers after hyperextension trauma].

Acute occlusion of digital arteries due to a sport injury A 33 year old female patient with acute ischaemia of the fingers I-II of the right hand was admitted to our emergency unit. She reported that this complete ischaemia had shortly occurred after a sport injury due to an extreme hyperflexion of the right hand in a volleyball match. Four days after this trauma she felt pain and paraesthesia in the right hand. Circular areas of ischaemia were developed with skin colour change to grey and dark blue. The primary measure of the blood pressure by doppler analysis showed no signals in the first and second finger. Initially she received 500 mg Aspirin by intravenous injection. The full therapeutic dose of LMWH related to the weight of the patient was given. On the basis of the short time interval between the occurrence of the symptoms and admission of the patient we decided to perform a so called retrograde intravenous injection. The aim of this therapy was the intraarterial lysis and reperfusion. The blood pressure in all fingers were nearly normal after three days. Daily intravenous transfusion of prostaglandin were given additionally. Necrosis could be prevented as a result of our treatment over seven days. At the end of our therapy only the skin epithelium of the second finger was slightly raised and showed a tendency to desquamation. All other fingers occurred in a normal colour.

Adult↗
PubMed2001

Phosphorylation of cytokeratin 8 and 18 in human vascular smooth muscle cells of atherosclerotic lesions and umbilical cord vessels.

Expression of cytokeratins (CK) is considered a hallmark of the state of epithelial differentiation. CK also occur in certain vascular smooth muscle cells (VSMC), inferring an association with a less differentiated phenotype. Recently, CK posttranslational modification was shown to occur in epithelial cells in stress, mitosis or apoptosis. The aim of this study was to determine potential CK phosphorylation patterns in human VSMC. Tissue samples of normal peripheral and coronary arteries, atherosclerotic lesions and umbilical cord vessels were evaluated by immunofluorescence microscopy applying antibodies specific for cytokeratins 8 and 18, specific cytokeratin phosphorylation sites, Ki-67-antigen as a proliferation marker and nick end labeling (TUNEL) to detect apoptosis. All samples contained cytokeratin-positive VSMC but diverse phosphorylation patterns. The C-terminal serine 431 of cytokeratin 8 (CK8Ser-431) was phosphorylated in the vast majority of CK-expressing VSMC of coronary artery lesions. Only a subset of these cells demonstrated phosphorylation of CK18Ser-33 or, to an even lesser extent, CK8Ser-73. DNA fragmentation occurred predominantly in samples containing cells with phosphorylated CK8Ser-431 domains. In contrast, occluded peripheral lesions exhibited little or no phosphorylation. Neonatal VSMC in umbilical cord vessels contain abundant phosphorylated CK domains, again predominantly CK8Ser-431, but also CK18Ser-33. Again, only single cells were found to be proliferating or to contain DNA fragmentation. Thus, abundant CK phosphorylation in VSMC of atherosclerotic lesions suggests a specific functional response to cell stress and a possible relation to apoptosis.

Aorta↗
PubMed2000

Cardiac alpha-actin in smooth muscle cells: detection in umbilical cord vessels and in atherosclerotic lesions.

Phenotypic modulation of smooth muscle cells (SMC) is a key event during the development of atherosclerotic and restenotic lesions. During this process, the composition of the cytoskeleton is substantially altered, with changes predominantly in actin expression reflecting a shift from smooth muscle alpha-actin to the non-muscle beta-isoform. We now demonstrate that yet another actin isoform, cardiac alpha-actin, is synthesized, de novo, in SMC of various atherosclerotic lesions. Using a highly specific monoclonal antibody against cardiac alpha-actin, we analyzed and compared the accumulation of this actin isoform in diverse SMC by immunofluorescence microscopy and immunoblotting. As expected, cardiac alpha-actin was present in human myocardium but not in healthy SMC of adult aorta, coronary arteries, trabeculae of the spleen, colon, stomach or skeletal muscle. Interestingly, the presence of cardiac alpha-actin was detected in umbilical cord vessels, human myometrium, in atherosclerotic coronary lesions and atherosclerotic lesions from peripheral vascular disease. The distribution of cardiac alpha-actin often paralleled that of cytokeratins 8 and 18, intermediate filament proteins typically found in dedifferentiated SMC. Taken together, the data presented here illustrate the expression of cardiac alpha-actin to be limited to either fetal vessels or those vessels or tissue having suffered damage or atrophy, outside its 'native' environment in the heart. The demonstration of cardiac alpha-actin in SMC of umbilical cord vessels and in atherosclerotic lesions but not in apparently healthy vessels supports the notion that SMC in atherosclerotic lesions exhibit a dedifferentiated phenotype.

Actins↗
PubMed2000

[Acute acral ischemia in all fingers possibly due to a Borrelia infection].

Acute interruption of circulation in the distal fingers can be both expression of an embolic event as well as the first manifestation of a vasculitis or collagenosis. The search for its cause is frequently difficult. In many cases a specialized analysis of the coagulation system as well as diagnostics such as ultrasound scan of the heart or a systematic antibody scanning do not reveal the origin of an embolus or the underlying disorder. On the basis of a case-report we would like to focus on a possible context between an infection of Borrelias stage III and consecutive deterioration of peripheral arterial perfusion in the fingers. Besides Jo-1- and positive sceleton-muscle-antibodies there were no serological and clinical indications for an autoimmune disease. It was possible to avoid acral necrosis by means of an antibiotic, immunosuppressive and rheological therapeutic concept. We recommend to control the borellia-antibody-level in cases of obscure threatening peripheral necrosis caused by arterial perfusion stop.

Acute Disease↗
PubMed1999

[Effect of common head gear on horses].

The functions of the most common head-gears for horses are analysed from a biomechanical point of view. With the exception of the stable halter are all of them designed to enlarge the tensile forces transmitted through the reins or the longe, and to concentrate the enlarged forces on sensitive parts of the horse's head: the nose, or the lips, mandible and tongue. Since the direction, duration and size of these tensile forces are the essential factors to modulate signals for controlling the horse, a device has been developed to measure, or at least roughly quantify these forces. The mechanical characteristics of bosal, caveçon, serreta, kappzaum and hackamore are demonstrated and compared with those of the two major types of bits: those with and without levers.

Animals↗
PubMed1994

[Sore throat patients as the topic of a general practice quality circle. Determination and development of a practice guideline. Quality Assurance Study group for General Medicine].

UNLABELLED: The present paper describes the institutionalization of a general practitioners' quality circle and the development of management guidelines for the treatment of patients with sore throat. Doctors participating: An invitation to attend an "information meeting" on the subject quality control and a quality circle sent to 200 general practitioners and internists, evoked a response by 18 physicians, ten of whom participated in the first meeting of the quality circle. Practical procedure: Stocktaking of the procedure in the doctor's office on the basis of a documentation questionnaire, the discussion of a video of the counselling of a patient with a sore throat, interviews with patients and the personal experience of the participating physicians was compared with a current analysis of the literature. The results of the comparison were taken as a basis for the development of management guidelines following the Dutch NHG Standard (Nederlands-Huisartsen-Genootschap-Standarden). RESULTS AND CONCLUSIONS: A wide variation was found in the treatment offered to patients with sore throats in the doctor's office. Deviation from text book information does not indicate a priori any quality deficit in the GP's practice. With respect to the management guideline worked out, it was agreed that in the individual case, a wellfounded deviation can be justified.

Family Practice↗
PubMed1994

Modulation of DNA supercoiling by interaction with netropsin and other minor groove binders.

The assay of DNA unwinding by ethidium, followed by sedimentation velocity techniques, was applied to complexes of supercoiled plasmid DNA with different non-intercalating drugs which strongly and sequence-specifically bind to DNA. Compared with the behaviour of naked DNA, most of the complexes exhibit an increase in the critical EB/nucleotide binding ratio associated with the principal minimum in the sedimentation profile. Using netropsin (Nt) as the paradigm of the minor groove binders investigated, the drug-induced alterations in various structural parameters of both the relaxed and supercoiled form of DNA are described. Whereas winding number, helical repeat (both being defined with reference to a surface normal), and linking number of the superhelical DNA remain constant in our experiments, its twist number, surface twist, number of superhelical turns as well as the absolute values of linking number difference, superhelix density, and writhing number increase on binding of Nt. Correspondingly, compared with the naked relaxed DNA a higher linking number (or twist number, or winding number), a higher average duplex winding angle and a lower helical repeat have to be assigned to the relaxed Nt-DNA complex. The various minor groove binders investigated were found to differ considerably in their efficiency to alter the structure of supercoiled DNA.

Base Sequence↗
PubMed1989

Structural differences between histone H1 molecules from sea urchin (Strongylocentrotus intermedius) sperm and calf thymus: hydrodynamic and c.d. studies.

Comparative sedimentation, diffusion and circular dichroism (c.d.) measurements have been performed on two histones H1 from sperm of the sea urchin Strongylocentrotus intermedius (H1S) and from calf thymus (H1T), at a high salt concentration of M NaCl. Both the Stokes radius and the frictional ratio derived from the hydrodynamic parameters were found to be somewhat smaller for H1S than the corresponding values for H1T. In view of the considerably higher molar mass of H1S compared with that of H1T, this result indicates that H+S in 2 M NaCl has a more compact conformation than H1T, probably due to a higher degree of secondary structure in the flanking domains of H1S. The c.d. measurements likewise show that H1S has a higher content of ordered structures than H1T. Model considerations indicate that the C-terminal tail of H1S is the main candidate for accommodation of these additional secondary structure regions.

Animals↗
PubMed1989

DNA binding protein from Streptomyces hygroscopicus: detection of binding by gel retardation, sedimentation and effects on the transcriptional activity in vitro.

The binding to supercoiled plasmid DNA as well as to double-stranded short DNA fragments of the DNA binding protein. ASBIII, from S. hygroscopicus has been demonstrated by gel retardation asay. As further revealed by sedimentation analysis, the protein-DNA complex formation also involves condensation of DNA and an aggregation step at higher total protein-to-DNA ratio (w/w). In vitro studies of the transcriptional activity of DNA-protein complexes showed that the ASBIII protein inhibits the overall template activity in the RNA polymerase II system to nearly similar extents for various DNA's. Preincubation of ASBIII-DNA complexes of different GC content, however, suggested a selective inhibitory effect on GC-rich DNA due to the higher stability of this complex. The results also indicate that the initiation of transcription of the GC-rich DNA template is affected by the ASBIII protein. The present results on the DNA binding properties and inactivation of the transcription of the ASBIII protein suggest that this protein may be a potential candidate for the local compaction of chromosomal DNA in Streptomyces hygroscopicus.

Animals↗
PubMed1985

Interaction of histone H1 from sea urchin sperm with superhelical and relaxed DNA.

Complexes of histone H1 from sea urchin sperm (H1S) and calf thymus (H1T) with superhelical DNA I and relaxed circular DNA II have been analyzed by analytical sedimentation. Similar to H1T, the highly basic and relatively arginine-rich histone H1S preferentially interacts with DNA I compared to DNA II under competition conditions. However, H1S induces a stronger aggregation of both forms of DNA than H1T. Below 0.05 M NaCl, the soluble complexes formed by both histones have similar properties, but aggregation proceeds in a different manner: H1S induces a stronger aggregation of DNA II as compared to DNA I, whereas H1T fails to aggregate DNA I. The results are explained on the basis of differences in amino acid sequence and structure of the two histones and related to the special chromatin condensing ability of histone H1S.

Animals↗
PubMed1979

Structural changes of ultraviolet-irradiated DNA derived from hydrodynamic measurements.

The paper reports on sedimentation and viscosity measurements performed on ultraviolet-irradiated DNA from T7 phage and calf thymus. From the hydrodynamic data the relative changes in the mean molecular weight, radius of gyration, and effective Kuhn statistical segment length were calculated. The results show that ultraviolet irradiation (254 nm) leads to a significant decrease of the effective statistical segment length of DNA which may be due to small local helix kinks (produced by the generation of photodimers) and a local increase of chain flexibility. Alterations in the overall DNA conformation may be observed even at low fluences where the mean molecular weight almost stays constant. The locally distorted helix regions possibly may serve as recognition sites in the first step of excision repair.

Animals↗