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Biomedical subjects

M Wunderlich

Publications and source records attributed to M Wunderlich.

At least 19 recordsLinked to original sources
PubMed2006

Hand-grip strength of young men, women and highly trained female athletes.

Hand-grip strength has been identified as one limiting factor for manual lifting and carrying loads. To obtain epidemiologically relevant hand-grip strength data for pre-employment screening, we determined maximal isometric hand-grip strength in 1,654 healthy men and 533 healthy women aged 20-25 years. Moreover, to assess the potential margins for improvement in hand-grip strength of women by training, we studied 60 highly trained elite female athletes from sports known to require high hand-grip forces (judo, handball). Maximal isometric hand-grip force was recorded over 15 s using a handheld hand-grip ergometer. Biometric parameters included lean body mass (LBM) and hand dimensions. Mean maximal hand-grip strength showed the expected clear difference between men (541 N) and women (329 N). Less expected was the gender related distribution of hand-grip strength: 90% of females produced less force than 95% of males. Though female athletes were significantly stronger (444 N) than their untrained female counterparts, this value corresponded to only the 25th percentile of the male subjects. Hand-grip strength was linearly correlated with LBM. Furthermore, both relative hand-grip strength parameters (F (max)/body weight and F (max)/LBM) did not show any correlation to hand dimensions. The present findings show that the differences in hand-grip strength of men and women are larger than previously reported. An appreciable difference still remains when using lean body mass as reference. The results of female national elite athletes even indicate that the strength level attainable by extremely high training will rarely surpass the 50th percentile of untrained or not specifically trained men.

Adult↗
PubMed2006

Recovery of hand grip strength and hand steadiness after exhausting manual stretcher carriage.

Rescue activities frequently require not only substantial and sustained hand-grip forces but also a subtle coordination of hand and finger muscles, e.g. when manipulating injection syringes after manual stretcher carriage. We investigated the recovery kinetics of manual coordination and muscle strength after exhausting stretcher carriage (4.5 km/h, load at each handle bar: 25 kg). Hand steadiness (frequency and duration of wall contacts when holding a metal pin into a small bore) and parameters of hand-grip strength were determined in 15 male volunteers before and immediately after the stretcher carriage. Measurements were repeated after 0.5, 1, 4 and 24 h of recovery. Mean carrying time was 215+/-87 s (SD), mean transport distance amounted to 264+/-104 m. During the carriage test, forces at the stretcher handles oscillated in the order of +/-50 N within each gait cycle. Immediately after exhaustion, hand steadiness was significantly deteriorated (threefold increase in frequency and duration of wall contacts), maximum and mean hand-grip force over 15 s were reduced by almost 20%. While the recovery of hand steadiness was complete by minute 30 after stretcher carriage, a significant reduction in maximum and mean hand-grip force by 12% could still be observed after 24 h. The present findings demonstrate that hand steadiness recovers much faster than maximum hand-grip strength after exhaustive manual stretcher carriage (less than 30 min vs. more than 24 h). Probably, muscle damage induced in particular by the eccentric components during stretcher transport seems to affect only the generation of large forces. By contrast, the generation and coordination of the much lower forces required for hand-steadiness appears to be impaired only during the short transient of metabolic recovery.

Adult↗
PubMed2006

Physical performance, body weight and BMI of young adults in Germany 2000 - 2004: results of the physical-fitness-test study.

In westernized countries the sedentary lifestyle in conjunction with a hypercaloric diet has caused an increase in the number of obese adults. Moreover, recent studies suggest that the prevalence of overweight in children increased during the last decade. However, the literature has to be interpreted with some caution since the majority of epidemiological studies examining health, fitness, and obesity rely on self-reported data rather than measurements. A further limitation is that most studies examine either physical activity or nutrition, only few deal with both aspects simultaneously. In the present study we analyzed both aspects in more than 58,000 persons aged between 17 and 26 years. All of them were applicants for the German Bundeswehr, which accepts only volunteers with school leaving certificates and a body mass index (BMI) below 30 kg . m (-2). The admitted subjects performed a Physical-Fitness-Test (PFT) consisting of 5 simple sport tests (shuttle run, sit-ups, push-ups, standing jump, Cooper test). For 23 000 subjects additional measurements of body height and body weight as well as information about their education level were available. These data were combined with the PFT results. We found large deficits in the physical fitness of young adults: More than 37 % of the participants failed to pass the PFT, with failure rates of the male volunteers increasing significantly since 2001. While the female volunteers showed virtually constant body weight and BMI, the corresponding values of men increased monotonously between the age of 17 and 26 years. Physical fitness was positively, BMI negatively correlated with education level. The present findings suggest that body weight increases and fitness decreases in non-obese young adults in Germany. Despite the correlations between BMI and physical fitness the terms "overweight" and "physically unfit" should not be regarded as synonyms.

Adolescent↗
PubMed2003

Two different heat shock transcription factors regulate immediate early expression of stress genes in Arabidopsis.

In order to assess the specific functional roles of different plant heat shock transcription factors (HSFs) we have isolated T-DNA insertion mutants in the AtHsf1 and AtHsf3 genes of Arabidopsis thaliana. Complete and selective loss of the promoter binding activities of AtHSF1 or AtHSF3, verified by immunoprecipitation assays, had no obvious effects on the heat shock (HS) response in the individual mutant lines. Only hsf1(-) /hsf3(-)double mutants were significantly impaired in HS gene expression. In these plants the inability to form high-molecular-weight HSE-binding complexes correlates with a dramatic change in the kinetics of mRNA accumulation from all HSF target genes tested, including members of the Hsp100, Hsp90, Hsp70 and small Hsp families, and genes for two heat-inducible class B-HSFs. After prolonged HS, the amounts of most heat shock mRNAs expressed, except transcripts of Hsp18.2, reached approximately the same levels as in wild type plants. Our data indicate that AtHSF1 and AtHSF3 are key regulators of the immediate stress-induced activation of HS gene transcription, and consequently determine the kinetics of the negative feed back loop that is responsible for the transience of HS gene expression in wild type.

Arabidopsis↗
PubMed2003

MEDIANOVO - a media database for medical education, research and health care.

MEDIANOVO provides a high quality, scientifically indexed multi-media database with comfortable authoring and download functions through a web-based frontend. Currently, MEDIANOVO is used by medical teachers as a repository for storing and sharing media for educational purposes. However a database was created which could also serve with training and further education, in computer based learning systems as well as medical publishers and for individual patient information. Through the web-frontend the content is available worldwide.

Databases as Topic↗
PubMed2001

Evaluation of perianal sepsis: comparison of anal endosonography and magnetic resonance imaging.

The purpose of this study was to compare prospectively the diagnostic yield of anal endosonography (AES) and magnetic resonance imaging (MRI) in the assessment of perianal fistulae and abscesses. There were 39 patients (14 men, 25 women; mean age, 40 years) who underwent AES, performed with a 10-MHz rotating endoanal probe and MRI at 1.0 T (axial and coronal T2-weighted turbo spin-echo (TSE) and turbo-STIR sequences). Fistulae were classified as subcutaneous, intersphincteric, transsphincteric, high (i.e., high extrasphincteric or suprasphincteric), rectovaginal, and horseshoe and were compared with the surgical findings in all patients. Overall, 58 fistulae (subcutaneous, N = 7; intersphincteric, N = 9; transsphincteric, N = 16; high, N = 17; rectovaginal, N = 5; and horseshoe, N = 4) were detected at surgery. MRI showed a sensitivity of 84% and AES of 60% (P <.05). False-positive diagnoses were made in 6 patients (15%) with MRI and in 15 patients (26%) with AES, for a specificity of 68% and 21%, respectively (P <.05). Our findings show that MRI is superior to AES in the assessment of fistula-in-ano before major surgery. AES should be used only for orientation before minor procedures, such as incision or drainage of subcutaneous fistulae.

Adult↗
PubMed2001

Bronchial artery perfusion during cardiopulmonary bypass does not prevent ischemia of the lung in piglets: assessment of bronchial artery blood flow with fluorescent microspheres.

OBJECTIVE: Blood supply of the lungs during total cardiopulmonary bypass (CPB) is limited to flow through the bronchial arteries. This study was undertaken to assess the bronchial artery blood flow during CPB with fluorescent microspheres in a piglet model. METHODS: We subjected ten piglets (mean weight 5.0+/-0.5 kg) to 120 min of normothermic, total CPB without aortic cross-clamping, followed by 60 min of post-bypass perfusion. Fluorescent microspheres were injected into the left atrium or the aortic cannula or distal to the cannula to assess bronchial artery blood flow before, during and after CPB. The reference samples were taken from the descending aorta. We compared the different sites of injection. Tissue samples of the lungs were taken before and 60 min after CPB. RESULTS: Before CPB, total bronchial artery perfusion was 43.6+/-14.1 ml/min (4.8+/-1.3% of cardiac output) as by injection distal to the aortic cannula. These values were not different when microspheres were injected into the left atrium or the aortic cannula. There was no difference in scatter or in the amount of microspheres in the reference samples among the three injections sites. During CPB, bronchial artery perfusion was significantly decreased (4.4+/-2.4 ml/min vs. 40.0+/-5.0 ml/min before CPB) and returned to baseline values 60 min after CPB. Light microscopy of the tissue samples revealed alveolar septal thickening and a decrease in alveolar surface area after 60 min of reperfusion which was associated with a decreased capacity to oxygenate blood. CONCLUSIONS: (1) Bronchial artery blood flow can quantitatively be assessed during CPB when microspheres are injected into the ascending aorta and the reference samples are taken from the descending aorta. (2) Despite adequate perfusion pressure bronchial artery blood flow is decreased substantially during CPB. (3) The decrease in blood flow and the ultrastructural changes present at the end of CPB suggest the presence of low-flow ischemia of the lung during total CPB.

Analysis of Variance↗
PubMed1998

Regulated expression of the homeobox gene, rPtx2, in the developing rat.

Using degenerate primers designed to amplify genes containing homeodomains, we have used reverse transcription and polymerase chain reaction to amplify and clone a rat homeobox gene. Based on the nucleotide and predicted amino acid sequences, the rat cDNA clone contains a high degree of sequence similarity to murine genes which are members of the paired-like class of homeobox genes (Ptx2, Otlx2, solurshin and Ptx1). Considering the high degree of sequence similarity and similar restricted expression patterns, we have named the cloned rat gene rPtx2 (rat Ptx2 homolog). Northern analysis revealed two rPtx2 transcripts expressed in the developing rat brain. Yet, only a single gene was detected by Southern blot hybridization, suggesting that multiple messages are the result of alternative transcriptional initiation, splicing or processing of a common message. The expression pattern of rPtx2 was further delineated by in situ hybridization to rat embryos. Within the brain, tissue specific expression was observed in the differentiating neural cells of the posterior hypothalamus, tegmentum, and rhombomere r1. Expression was also observed in the developing pituitary, maxilla, mandible, tongue and umbilical cord. To further study the control of Ptx2 gene expression, we used an in vitro model for neural differentiation by treating mouse embryonic stem cells with retinoic acid. Within 24 h and prior to detection of a neural phenotype in the culture, murine Ptx transcripts were induced and remained elevated for at least 6 days. This suggests that retinoic acid may be an important inductive signal which regulates the developmental and tissue-specific expression of Ptx2.

Aging↗
PubMed1998

Embryonic stem cells as a model for studying regulation of cellular differentiation.

Mouse embryonic stem (ES) cells can be differentiated in vitro into near homogeneous populations of both neurons and skeletal muscle as well as other cell types. We previously showed that treatment of pluripotent ES cells with retinoic acid (RA) induced differentiation into highly enriched populations of gamma-aminobutyric acid (GABA) expressing neurons. The reasons for generation of only GABA neurons as opposed to other neuronal cell types were not known. We have extended our previous work and now show that with RA induction of ES cells we not only obtain GABA neurons, but also dopaminergic neurons. Critical for the production of dopaminergic neurons after RA induction was the post-induction plating conditions used. No dopaminergic neurons were detected if cells were plated in serum-free media optimized for neuronal survival. However, significant numbers of dopamine neurons could be detected when cells were plated in media containing fetal calf serum. These observations support the conclusion that RA acts as a general neural inducing agent and that conditions post-induction either selectively support survival of a particular class of neuronal cells or that the conditions post-induction actually further instruct cells to differentiate into different types of neurons.

Animals↗
PubMed1998

[Prolapse of the small intestine through a surgically closed introitus vaginae after vaginal hysterectomy followed by subsequent colpectomy].

We report on an unusual case of small bowel prolapse through a hiatus in the closed introitus vaginae after previous total colpectomy. The interval between colpectomy and present prolapse was nearly 4 years. The intestinum was reponated by abdominal approach, but a partial resection of the small bowel was not to avoid. The possible complications after vaginal hysterectomy resp. colpectomy are discussed. According to literature we didn't find a similar case.

Aged↗
PubMed1997

Fetal pig neural cells as a restorative therapy for neurodegenerative disease.

With proper immunosuppression, interspecies transplantation of porcine as well as other species of neural cells survive, mature, and integrate into the host in a manner which reconstructs much of the appropriate neural circuitry. These transplants have been shown to alleviate many of the symptoms of various disorders of the central nervous system. In this study, we addressed immunological and maturation issues with regards to intracerebral transplantation of fetal porcine neural cells. First, we compared fetal neural xenograft survival in athymic nude rats versus rats immunosuppressed with cyclosporin A and found that there is little discernible difference between porcine grafts in the 2 recipients. We also found that ectopic transplantation of cells isolated from the porcine striatal primordium can survive and develop into grafts composed of both neuronal and glial phenotypes within the rat hippocampus. This fact raises the possibility that cells of a particular neurotransmitter type (e.g., GABAergic cells) developing from the striatal precursor cells can be transplanted outside the striatum of the adult brain and have physiological effects.

Animals↗
PubMed1996

Competition between DsbA-mediated oxidation and conformational folding of RTEM1 beta-lactamase.

Similar to other proteins of the periplasm of Escherichia coli, TEM 1 beta-lactamase contains only a single disulfide bond. It can fold to its native conformation in both the presence and the absence of this disulfide bond. The GdmC1-dependent equilibrium unfolding of beta-lactamase in vitro is well described by a N reversible I reversible U three-state model in which the native protein (N) first reacts to an intermediate of the molten globule type (I) and then to the unfolded state (U). We find that the disulfide bond of beta-lactamase stabilizes I relative to U, but does not change the stability of N relative to I. The I reversible U transition is an extremely rapid reaction for both reduced and oxidized beta-lactamase, but the N reversible I folding kinetics are slow and identical in the presence and the absence of the disulfide bond. This insensitivity of the N reversible I equilibrium and kinetics suggests that the region around the disulfide bond is already native-like folded and is presumably buried in the intermediate I, prior to the slow and rate-limiting events of folding. This was confirmed by measuring the stability of the disulfide bond, which, to a first approximation, is identical in N and I. In native, reduced beta-lactamase, the thiol groups are inaccessible for oxidation by DsbA, but at the stage of the molten globule intermediate I oxidation is still possible, because I is in fast exchange with the unfolded protein U. The introduction of the disulfide bond into beta-lactamase by DsbA competes with conformational folding at the stage of the final slow steps in the folding of the reduced protein. The major problem in the oxidation of proteins with one or two disulfide bonds (such as beta-lactamase) is not the formation of incorrect disulfide bonds, but the premature burial of the thiol groups by the rapid conformational folding of the reduced protein. DsbA, the major thiol/ disulfide isomerase of the bacterial periplasm, meets this problem. It is a very strong oxidant, and its reaction with cysteine residues in unfolded proteins is extremely fast.

Disulfides↗
PubMed1996

Preferential binding of an unfolded protein to DsbA.

The oxidoreductase DsbA from the periplasm of escherichia coli introduces disulfide bonds into proteins at an extremely high rate. During oxidation, a mixed disulfide is formed between DsbA and the folding protein chain, and this covalent intermediate reacts very rapidly either to form the oxidized protein or to revert back to oxidized DsbA. To investigate its properties, a stable form of the intermediate was produced by reacting the C33A variant of DsbA with a variant of RNase T1. We find that in this stable mixed disulfide the conformational stability of the substrate protein is decreased by 5 kJ/mol, whereas the conformational stability of DsbA is increased by 5 kJ/mol. This reciprocal effect suggests strongly that DsbA interacts with the unfolded substrate protein not only by the covalent disulfide bond, but also by preferential non-covalent interactions. The existence of a polypeptide binding site explains why DsbA oxidizes protein substrates much more rapidly than small thiol compounds. Such a very fast reaction is probably important for protein folding in the periplasm, because the accessibility of the thiol groups for DsbA can decrease rapidly when newly exported polypeptide chains begin to fold.

Disulfides↗
PubMed1996

Don't ask, they won't tell: the quality of adolescent health screening in five practice settings.

OBJECTIVES: This study examined the extent to which comprehensive, age-appropriate adolescent health screening is undertaken in the clinical setting and whether the extent of such screening varies by setting. METHODS: Charts of adolescents 13 to 17 years old (n = 788) were randomly selected from five practice settings in Minneapolis, Minn. Each was assessed for the number of biomedical and sociobehavioral health risks screened. RESULTS: In no practice setting was there screening to the level recommended. The two teen clinics screened more extensively for behavioral, psychosocial, substance use and sexual behavior risks than the community family practice setting, which, in turn, screened more extensively than either the private family practice or private pediatric practice settings, which did not differ from each other. Age differences and gender accounted for only small amounts of variance in total number of health risks screened, whereas differences among practice settings accounted for a larger amount. CONCLUSIONS: Results suggest substantive deficiencies in private practice settings' implementation of preventive care screening protocols for adolescents.

Adolescent↗
PubMed1995

A bacterial thioredoxin-like protein that is exposed to the periplasm has redox properties comparable with those of cytoplasmic thioredoxins.

The membrane-anchored thioredoxin-like protein (TlpA) from the Gram-negative soil bacterium Bradyrhizobium japonicum was initially discovered due to its essential role in the maturation of cytochrome aa3. A soluble form of TlpA lacking the N-terminal membrane anchor acts as a protein thiol:disulfide oxidoreductase. TlpA possesses an active-site disulfide bond common to all members of the thiol:disulfide oxidoreductase family. In addition, it contains two non-active-site cysteines that form a structural disulfide bond (Loferer, H., Bott, M., and Hennecke, H. (1993) EMBO J. 12, 3373-3383; Loferer, H., and Hennecke, H. (1994) Eur. J. Biochem. 223, 339-344). Here, we compare the far- and near-UV CD spectra of TlpA before and after reduction of both disulfides by dithiothreitol and show that the non-active-site disulfide bond is not required for the integrity of TlpA's native conformation. In contrast to dithiothreitol, reduced glutathione (GSH) selectively reduces the active-site disulfide and leaves the non-active-site disulfide bond intact, even at high molar excess over TlpA. The selective reduction of the active-site disulfide bond leads to a 10-fold increase of the intrinsic tryptophan fluorescence of TlpA at 355 nm, which may be interpreted as a quenching of tryptophan fluorescence by the active-site disulfide bond. Using the specific fluorescence of TlpA as a measure of its redox state, a value of 1.9 +/- 0.2 M was determined for the TlpA:glutathione equilibrium constant at pH 7.0, demonstrating that TlpA is a reductant, like cytoplasmic thioredoxins. The DsbA protein, which acts as the final oxidant of periplasmic secretory proteins in Escherichia coli, is not capable of oxidizing the active-site cysteines of TlpA. This suggests that TlpA's primary role in vivo is keeping the thiols of certain proteins reduced and that TlpA's active, reduced state may be maintained owing to its kinetically restricted oxidation by other periplasmic disulfide oxidoreductases such as DsbA.

Bacterial Proteins↗
PubMed1995

Determination of the three-dimensional structure of the bifunctional alpha-amylase/trypsin inhibitor from ragi seeds by NMR spectroscopy.

The three-dimensional structure of the bifunctional alpha-amylase/trypsin inhibitor (RBI) from seeds of ragi (Eleusine coracana Gaertneri) has been determined in solution using multidimensional 1H and 15N NMR spectroscopy. The inhibitor consists of 122 amino acids, with 5 disulfide bridges, and belongs to the plant alpha-amylase/trypsin inhibitor family for which no three-dimensional structures have yet been available. The structure of the inhibitor was determined on the basis of 1131 interresidue interproton distance constraints derived from nuclear Overhauser enhancement measurements and 52 phi angles, supplemented by 9 psi and 51 chi 1 angles. RBI consists of a globular four-helix motif with a simple "up-and-down" topology. The helices are between residues 18-29, 37-51, 58-65, and 87-94. A fragment from Val 67 to Ser 69 and Gln 73 to Glu 75 forms an antiparallel beta-sheet. The fold of RBI represents a new motif among the serine proteinase inhibitors. The trypsin binding loop of RBI adopts the "canonical", substrate-like conformation which is highly conserved among serine proteinase inhibitors. The binding loop is stabilized by the two adjacent alpha-helices 1 and 2. This motif is also novel and not found in known structures of serine proteinase inhibitors. The three-dimensional structure of RBI together with biochemical data suggests the location of the alpha-amylase binding site on the face of the molecule opposite to the site of the trypsin binding loop. The RBI fold should be general for all members of the RBI family because conserved residues among the members of the family from the core of the structure.

Amino Acid Sequence↗
PubMed1995

Efficient catalysis of disulfide formation during protein folding with a single active-site cysteine.

Protein disulfide isomerases (PDIs) catalyze disulfide bond formation during protein folding in vivo and are essential for viability in eukaryotic cells. They share the active-site sequence C-X-X-C that forms a catalytic disulfide. The recent finding that the EUG1 protein, a PDI-related yeast protein, with C-X-X-S sequence at its active sites can complement PDI-deficiency raised the general question of whether disulfide-isomerase activity is essential for cell viability or whether PDI variants with single active-site thiol groups can be catalytically active as disulfide isomerases. We investigated the function of the catalytic cysteine residues in DsbA, a PDI-related protein required for disulfide formation in the periplasmic space of Escherichia coli, by replacing C30 and C33 with alanine. While the mutant C30A and the double mutant CC30/33AA are inactive, C33A catalyzes disulfide-interchange reactions and oxidative renaturation of the reduced, unfolded thrombin inhibitor hirudin with close to wild-type efficiency. Thus, the single active-site thiol group of C30 is sufficient for disulfide-isomerase activity of the DsbA protein.

Base Sequence↗