Biomedical subjects

K Weber

Publications and source records attributed to K Weber.

At least 73 records · Page 4Linked to original sources

PubMed2001

Urine catecholamine concentrations and psychophysical stress in elite tennis under practice and tournament conditions.

BACKGROUND: The purpose of the study was to specify and define the differences of psychophysical stress in elite tennis players under practice and tournament conditions. METHODS: Basal, pre- and postcompetition urine samples of 26 nationally ranked players (NR) were analysed for concentrations of epinephrine (EPI) and norepinephrine (NE) under practice (P) and tournament conditions (T). Results were completed by the values obtained from two internationally ranked players (IR) competing in 6 (player A) and 5 (player B) Davis-Cup matches, respectively. RESULTS: In NR, pre- and postcompetition concentrations for EPI were significantly higher under tournament conditions (T: 1.33+/-0.65 and 3.66+/-2.51 microg/100 mg creatinine vs P: 0.61+/-0.39 and 0.97+/-0.59 microg/100 mg creatinine). The NE/EPI ratio showed significantly inverse results (T: 3.53+/-1.87 and 3.58+/-1.59 vs P: 8.08+/-6.99 and 10.03+/-6.58), whereas the concentration of NE did not differ between the two conditions. Significant correlations were found between the level of perceived nervousness (ten-point-likert scale) and the postcompetition concentration of EPI (r=0.491, p<0.05) and the NE/EPI ratio (r=-0.595, p<0.01). Players who felt affected by nervousness in their performance outcome showed significantly lower NE/EPI ratios (2.73+/-1.44 vs 4.49+/-2.54, p<0.05). The Davis-Cup-Players showed intra-individually constant but inter-individually different concentrations of EPI (A= 2.2+/-0.5 vs B= 7.0+/-0.8 microg/100 mg creatinine), NE (A= 7.4+/-2.2 vs B= 15.5+/-3.2 microg/100 mg creatinine) and the ratio of NE/EPI (A= 3.7+/-2.2 vs B= 2.2+/-0.7). CONCLUSIONS: In tennis tournaments, sympathetic activity is increased due to a higher psychological stress which may impair performance. Practical efforts should focus on psycho-regulative methods and psychophysical regeneration for players dealing with a chronic sympathetic hyper-activation.

Adult↗

PubMed2001

[Cost-effectiveness of PET in the management algorithms of lung tumors: comparison of health economic data].

Modelling is an accepted, valid and often necessary method for assessing economic effectiveness in terms of cost per life year gained. Comparing an alternative strategy (a) with a baseline strategy (bl), the incremental cost (COSTa-COSTbl) divided by the incremental life expectancy (LEa-LEbl) defines the incremental cost-effectiveness ratio (ICER). Taking watchful waiting as the low-cost baseline strategy for the management of solitary pulmonary nodules, the ICER of positron emission tomography (PET) [3218 euros (EUR) per life year saved (LYS)] was more favourable than that of exploratory surgery (4210 EUR/LYS) or that of transthoracic needle biopsy (6120 EUR/LYS). Changing the baseline strategy to exploratory surgery, the use of PET led to cost savings and additional life expectancy in case of an intermediate pretest probability of malignancy. For management of potentially operable non-small cell lung cancer the use of PET in patients with normalisized mediastinal lymph nodes on CT was most cost-effective (143 EUR/LYS), and the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. Using PET in patients with enlarged lymph nodes on CT, the ICER raised to 36,667 EUR/LYS. When PET or CT were positive for mediastinal lymph nodes, the exclusion from biopsy confirmation led to cost savings that did not justify the expected reduction in life expectancy. Economic data from the USA and Japan also demonstrated the cost-effectiveness of PET-based algorithms for the management of lung tumours.

Algorithms↗

PubMed2001

Crash protection for children in ambulances.

The objectives of the study were to determine the most effective and reliable means of restraining children on an ambulance cot and to develop recommended field procedures for emergency medical service providers. A series of crash tests at 48 km/h were conducted using convertible child restraints, car beds, and harness systems tested with 3-year, infant, and 6-year size dummies. Belt configuration and backrest position were varied. A new cot and fastener system significantly improved restraint performance over older systems previously tested. A two-belt attachment with elevated cot backrest was found to be the method with the least performance variability for securing either a convertible child restraint or a car bed. It was concluded that children who weight up to 18 kg, fit in a convertible child restraint, and can tolerate a semi-upright seated position can be restrained in a convertible child restraint secured with two belts to an ambulance cot. Infants who must lie flat can be restrained in a car bed modified for two seatbelt paths and secured to a cot. In each case, the cot backrest must be elevated, and the cot and anchor system must be crashworthy. None of the harness configurations tested proved to be satisfactory, but an effective system could be developed by following accepted restraint design principles.

Accidents, Traffic↗

PubMed2000

Enantiopure 4- and 5-aminopiperidin-2-ones: regiocontrolled synthesis and conformational characterization as bioactive beta-turn mimetics.

Starting from aspartic acid, we synthesized lactam-bridged beta- and gamma-amino acid equivalents. Using the 1,4-bis-electrophile 1b as a central intermediate, the 4- and 5-aminopiperidin-2-ones 4 and 8, respectively, were approached by regioselective functionalization and subsequent lactamization. Diastereoselective C-alkylation was performed after N-protection of the lactam functionality when exclusive trans configuration resulting in the formation of 5a-f was observed in the 4-amino series. On the other hand, cis selectivity was typical for the alkylations of the 5-amino lactams 5a,b. To investigate the ability of the lactam building blocks to induce reverse-turn structures by intramolecular hydrogen bonding, the model peptidomimetics 12 and 14 representing Homo-Freidinger lactams of type II and III were prepared from 4a and 8a, respectively. Conformational analyses in dilute solution (1 mM) by IR and NMR spectroscopy at room temperature clearly indicated that the 4-aminopiperidin-2-one derivative 12 predominantly adopts a reverse-turn structure stabilized by a CO-HN hydrogen bond in an 11-membered ring. VT NMR experiments showed a substantial temperature dependency of the terminal NH when Deltadelta(NH)/DeltaT = -6.5 indicated that the amount of intramolecular hydrogen bonding is higher at low temperature. An application in the field of medicinal chemistry was demonstrated. Thus, starting from the Homo-Freidinger lactam 11c and the enantiomer ent-11c, we synthesized the peptidomimetics 15c and 16c and investigated them as lactam-bridged analogues of the dopamine receptor modulating peptide Pro-Leu-Gly-NH(2) (PLG). Both test compounds turned out to enhance significantly the agonist binding of dopamine D2 receptors, when the isomer 15c revealed a potency comparable to the genuine ligand PLG.

Animals↗

PubMed2000

GAS41, a highly conserved protein in eukaryotic nuclei, binds to NuMA.

The yeast two-hybrid system was used to identify binding partners of NuMA, a component of the nuclear matrix in interphase cells. By using the C-terminal half of NuMA as bait, a human cDNA sequence coding for a 223-amino acid protein with a non-helical N-terminal domain and a C-terminal alpha-helical portion was identified and fully sequenced. It was identical to GAS41, a sequence amplified in human gliomas. The sequence of the homologous Drosophila protein was established, and the alignment for GAS41 from nine different species showed that GAS41 is a general eukaryotic protein found in species as diverse as Arabidopsis, Drosophila, Caenorhabditis elegans, yeast, and man. Northern blot analysis showed a single transcript in eight human tissues. A polyclonal antibody to GAS41 showed a dotted staining pattern in interphase nuclei and a uniform distribution in mitotic cells. A GFP-GAS41 fusion protein displayed equivalent patterns. In vitro GAS41 bound to the C-terminal part of the rod region of NuMA, as shown by dot overlay and by surface plasmon resonance measurements. The K(d) of the complex was 2 x 10(-)(7) m. GAS41 is related to the AF-9 and ENL proteins, which are putative transcription factors found as fusion proteins in some acute leukemias. The NuMA/GAS41 interaction may provide a link between nuclear structure and gene expression.

Amino Acid Sequence↗

PubMed2000

Tunicates have unusual nuclear lamins with a large deletion in the carboxyterminal tail domain.

Lamins are essential proteins of metazoa. They give rise to the nuclear lamina lining the nucleoplasmic face of the inner nuclear membrane. Here we report the isolation of complete lamin cDNA clones from three urochordate (tunicate) libraries - adult Ciona intestinalis, the tailbud stage of Styela clava and the gastrula stage of Molgula oculata. Lamins L1 and L2 of adult Ciona are derived from two distinct genes. The sequence of the 3' part of the Ciona lamin L1 gene shows that the alpha and beta variants of lamin L1 in Ciona and Styela arise by alternative choice of the 5' splice site at the last intron. Strikingly, all urochordate sequences reveal a 90 residue deletion which removes nearly the entire 105-box. This region is the only long sequence homology segment in the carboxyterminal tail domain of lamins from animals as diverse as Hydra, Drosophila, Priapulus, Caenorhabditis elegans, several echinoderms, the cephalochordate Branchiostoma and various vertebrates. We discuss this unexpected plasticity of lamin sequences as a urochordate specific marker. To increase the database for the chordates we completed the partial sequence of the Branchiostoma lamin by the N-terminal head and central rod domains. The molecular phylogenetic analysis of the metazoan lamin sequences emphasises the monophyletic nature of the chordates in line with the morphological evidence.

Alternative Splicing↗

PubMed2000

Alendronate for the treatment of osteoporosis in men.

BACKGROUND: Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study. There have been no large, controlled trials of treatment in men. METHODS: In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis. Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations. Men with other secondary causes of osteoporosis were excluded. All the men received calcium and vitamin D supplements. The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density. RESULTS: The men who received alendronate had a mean (+/-SE) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine, 2.5+/-0.4 percent at the femoral neck, and 2.0+/-0.2 percent for the total body (P<0.001 for all comparisons with base line). In contrast, men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent (P<0.001 for the comparison with base line) and no significant changes in femoral-neck or total-body bone mineral density. The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001). The incidence of vertebral fractures was lower in the alendronate group than in the placebo group (0.8 percent vs. 7.1 percent, P=0.02). Men in the placebo group had a 2.4-mm decrease in height, as compared with a decrease of 0.6 mm in the alendronate group (P=0.02). Alendronate was generally well tolerated. CONCLUSIONS: In men with osteoporosis, alendronate significantly increases spine, hip, and total-body bone mineral density and helps prevent vertebral fractures and decreases in height.

Adult↗

PubMed2000

Cloning and recombinant expression of the La RNA-binding protein from Trypanosoma brucei.

We report the isolation, cloning and recombinant expression of a Trypanosoma brucei homolog of the La RNA-binding protein. Based on peptide sequence information we have isolated a cDNA clone which encodes a protein of 335 amino acids with a predicted molecular weight of 37.7 kDa. The amino acid sequence fits the domain structure of known La proteins and contains a putative ATP-binding site located in the COOH-terminal domain. The cDNA was expressed as a glutathione S-transferase fusion protein in Escherichia coli, and the recombinant protein displayed RNA-binding activity in an electrophoretic mobility shift assay.

Amino Acid Sequence↗

PubMed2000

Variable bone mass recovery in hyperthyroid bone disease after radioiodine therapy in postmenopausal patients.

OBJECTIVES: Long-term follow-up of postmenopausal hyperthyroid females after radioiodine therapy, since hyperthyroidism is known to cause impressive bone loss which may increase the risk of bone fractures. METHODS: Bone mineral density (BMD) and biochemical parameters of bone metabolism in hyperthyroid postmenopausal patients were investigated before and 2 years after radioiodine therapy and compared with euthyroid age-matched controls. RESULTS: At baseline, the incidence of low BMD with t-scores more than 2.5 S.D. below normal was significantly higher in hyperthyroid patients (54%) than in controls (20%, P<0.001). Regardless of initial BMD values, osteocalcin (OC) was also higher in all hyperthyroid patients (P<0.0001). After 2 years, all treated patients were euthyroid and OC levels were in the upper normal range. In hyperthyroid patients with initially low BMD, bone density values had increased significantly by +6.5% (P<0.008) as compared with baseline values. In contrast, hyperthyroid patients with initially normal BMD showed a further decrease in lumbar BMD values of -4.3% despite radioiodine treatment. BMD in euthyroid controls decreased by -6.5% within 2 years. CONCLUSIONS: We conclude that hyperthyroid postmenopausal patients with generally increased bone turnover may show individual differences in bone loss and BMD recovery after radioiodine treatment. The mechanisms for this variable manifestation of osteoporosis have still to be elucidated, since this has implications for prophylactic and therapeutic strategies in these elderly patients.

Aged↗

PubMed2000

Treatment of N,N-dibenzylamino alcohols with sulfonyl chloride leads to rearranged beta-chloro amines, precursors to beta-amino acids, and not to tetrahydroisoquinolines.

[reaction: see text] Very recently, the unexpected formation of 3-substituted 1,2,3,4-tetrahydroisoquinolines starting from N,N-dibenzyl-protected beta-amino alcohols was reported. The authors claimed that treatment with tosyl chlorides induced intramolecular Friedel-Crafts alkylation. Reexamination of the reactions in our laboratory clearly proved rearranged chloro amines instead of the initially assumed tetrahydoisoquinoline structures. The chloro amines investigated can be employed as highly useful intermediates for an EPC synthesis of beta-amino nitriles and beta-amino acids.

Amines↗

PubMed2000

Characterization of muscle filamin isoforms suggests a possible role of gamma-filamin/ABP-L in sarcomeric Z-disc formation.

Filamin, also called actin binding protein-280, is a dimeric protein that cross-links actin filaments in the cortical cytoplasm. In addition to this ubiquitously expressed isoform (FLN1), a second isoform (ABP-L/gamma-filamin) was recently identified that is highly expressed in mammalian striated muscles. A monoclonal antibody was developed, that enabled us to identify filamin as a Z-disc protein in mammalian striated muscles by immunocytochemistry and immunoelectron microscopy. In addition, filamin was identified as a component of intercalated discs in mammalian cardiac muscle and of myotendinous junctions in skeletal muscle. Northern and Western blots showed that both, ABP-L/gamma-filamin mRNA and protein, are absent from proliferating cultured human skeletal muscle cells. This muscle specific filamin isoform is, however, up-regulated immediately after the induction of differentiation. In cultured myotubes, ABP-L/gamma-filamin localises in Z-discs already at the first stages of Z-disc formation, suggesting that ABP-L/gamma-filamin might play a role in Z-disc assembly.

3T3 Cells↗

PubMed2000

[Patellar tendon rupture after anterior cruciate ligament reconstruction with autologous patellar tendon-bone transplant. A case report].

Patellar ligament ruptures due to a complication after usage of bone-tendon autograft for an anterior cruciate ligament reconstruction happens seldom. During surgeries to restore continuity a fascia-lata-strip may be wrapped in and fixated to secure the primary tendon suture. This may be done in addition to the usually employed patella-tibial wiring cerclage. Whether a matrix for the scarred healing tendon will be created in addition to the construction of a support for the primary tendon seam without a foreign body reaction has to be left to further histological clarifications that cannot be implemented in the present casuistry.

Adult↗

PubMed2000

Influence of body composition on quantitative ultrasound parameters of the os calcis in a population-based sample of pre- and postmenopausal women.

Body mass is known to be related to measures of bone mineral density (BMD) as well as to parameters of quantitative ultrasound (US). To examine the effect of the body compartment's fat mass and lean body mass on quantitative ultrasonic bone parameters, data from a sample of 3241 German women were analyzed. Anthropometric measures, including skinfold thickness, were obtained from standardized measurements, and fat and lean body mass were derived from classical regression formulas based on skinfold measurements. Ultrasonic bone measurements were performed on the right os calcis, and speed of sound (SOS) and broadband ultrasound attenuation (BUA) were determined. Women were grouped into pre- and postmenopausal status; postmenopausal women were further stratified into ever and never hormone-replacement user. Correlation analysis indicated lean body mass to be stronger correlated with BUA than fat mass in both pre- (r = 0.23; P = 0.0001) and postmenopausal women with (r = 0.19; P = 0.0001) and without hormone replacement therapy (HRT) (r = 0.26; p = 0.0001). SOS demonstrated very small or no associations with body mass or its components. Multiple linear regression models were used to describe the relationship among body weight, fat mass, and lean body mass on BUA after adjustment for confounding variables. Both in pre- and postmenopausal women lean body mass was more strongly related to BUA than fat mass. However, body mass measures explained only small amounts of the overall variance in BUA (R(2) = 1-3% in premenopausal women; R(2) = 1% postmenopausal with HRT; R(2) = 4-5% in postmenopausal women without HRT). In conclusion, the strong influence of body mass and its components previously reported for BMD was not observed for quantitative ultrasonic bone parameters.

Adult↗

PubMed2000

Cost-effectiveness of FDG-PET for the management of solitary pulmonary nodules: a decision analysis based on cost reimbursement in Germany.

Management of solitary pulmonary nodules (SPNs) of up to 3 cm was modelled on decision analysis comparing "wait and watch", transthoracic needle biopsy (TNB), exploratory surgery and full-ring dedicated positron emission tomography (PET) using fluorine-18 2-fluorodeoxyglucose (FDG). The incremental cost-effectiveness ratios (ICERs) were calculated for the main risk group, a cohort of 62-year-old men, using first "wait and watch" and second exploratory surgery as the baseline strategy. Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.95 and 0.80 for detecting malignancy in SPNs and at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes. The costs quoted correspond to reimbursement in 1999 by the public health provider in Germany. Decision analysis modelling indicates the potential cost-effectiveness of the FDG-PET strategy for management of SPNs. Taking watchful waiting as the low-cost baseline strategy, the ICER of PET [3218 euros (EUR) per life year saved] was more favourable than that of exploratory surgery (4210 EUR/year) or that of TNB (6120 EUR/year). Changing the baseline strategy to exploratory surgery, the use of PET led to cost savings and additional life expectancy. This constellation was described by a negative ICER of -6912 EUR/year. The PET algorithm was cost-effective for risk and non-risk patients. However, the ICER of PET as the preferred strategy was sensitive to a hypothetical deterioration of any PET parameters by more than 0.07. To transfer the diagnostic efficacy from controlled studies to the routine user and to maintain the cost-effectiveness of this technology, obligatory protocols for data acquisitions would need to be defined. If the prevalence of SPNs is estimated at the USA level (52 per 100,000 individuals) and assuming that multiple strategies without PET are the norm, the overall costs of a newly implemented PET algorithm would be limited to far less than one EUR per member of the public health provider in Germany.

Biopsy, Needle↗

PubMed2000

Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results.

Decision analysis is used here to establish the most cost-effective strategy for management of potentially operable non-small cell lung cancers (NSCLCs). The strategies compared were conventional staging (strategy A), dedicated systems of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) in patients with normal-sized (strategy B) or in patients with enlarged mediastinal lymph nodes (part of strategy C), and FDG-PET followed by exclusion from surgical procedures when both computed tomography (CT) and PET were positive for mediastinal lymph nodes (strategy D) or when PET alone was positive (strategy E). Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes, and at 0.95 and 0.76 when these lymph nodes were enlarged. The calculated probability of up-staging to M1 by using PET was 0.05. The costs quoted correspond to the cost reimbursed in 1999 by the public health provider in Germany. The incremental cost-effectiveness ratio (ICER) of strategy B was much more favourable (143 EUR/LYS; LYS = life year saved) than the ICER of strategy C (36,667 EUR/LYS). In strategy B, the use of PET did not raise the overall costs because the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. The exclusion from biopsy confirmation in strategies D and E led to cost savings that did not justify the expected reduction in life expectancy. In sensitivity analyses, the ICERs of strategy B were robust to the pretest likelihood of N2/N3, to penalized test parameters of PET and to reimbursement of PET. However, the ICER of strategy B would be raised to 28,000 EUR/LYS through use of thoracic PET without whole-body scanning. To conclude, the implementation of whole-body PET with a full ring of detectors in the preoperative staging of patients with NSCLC and normal-sized lymph nodes is clearly cost-effective. However, patients with nodal-positive PET results should not be excluded from biopsy.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Reconstitution of NK cell activity in HIV-1 infected individuals receiving antiretroviral therapy.

We studied natural immunity mediated by natural killer (NK) cells in 62 HIV-1 infected individuals, 54 HIV-1 infected individuals receiving highly active antiretroviral therapy (HAART) for more than one year and 8 HIV-1 infected individuals without antiretroviral therapy. 22 individuals had a complete suppression of viral replication characterized by viral load values <50 copies/ml, whereas 32 individuals presented with persistent viral replication. The 8 untreated patients had an indication to start antiretroviral treatment. Lytic activity of NK cells was measured in a 51chromium release assay. In patients with persistent viral replication under HAART NK cell activity was significantly decreased compared to patients with effective control of HIV viremia. Patients with complete suppression of HIV replication displayed a similar NK activity to healthy control persons. Differences in antibody-dependent cellular cytotoxicity (ADCC) were not observed. Further studies will investigate whether decreased NK cell activity is a reason for or the consequence of persistent viral replication.

Antibody-Dependent Cell Cytotoxicity↗

PubMed2000

Progressive reduction of CMV-specific CD4+ T cells in HIV-1 infected individuals during antiretroviral therapy.

Visualization of antigen-specific T cells has become an important tool in studying immune responses. The aim of this study was to analyze CMV-specific CD4+ T cells in healthy and HIV-infected individuals. Peripheral blood mononuclear cells (PBMC) were examined for antigen-induced intracellular cytokine responses. We found significant numbers of CMV-specific CD4+ T cells detectable in most CMV-IgG+ HIV-1 infected individuals, whereas CMV-specific CD4+ T cells could not be demonstrated in CMV-IgG- patients. Median frequency of CMV-specific CD4+ T cells were lower in HIV-infected subjects who had been treated with highly active antiretroviral therapy (HAART) for more than 1 year than in untreated HIV-infected individuals. In patients under therapy for less than 1 year median CMV-specific CD4+ T cell responder frequency was higher than in subjects treated for more than 1 year but lower than in untreated subjects. HIV suppression with HAART might lead to a progressive reduction of CMV-specific CD4+ T cells indicating an efficient elimination of an opportunistic pathogen.

Adult↗

PubMed2000

The epidermal intermediate filament proteins of tunicates are distant keratins; a polymerisation-competent hetero coiled coil of the Styela D protein and Xenopus keratin 8.

Two novel cytoplasmic intermediate filament (IF) proteins (C and D) from the tunicate (urochordate) Styela are characterised as putative keratin orthologs. The coexpression of C and D in all epidermal cells and the obligatory heteropolymeric IF assembly of the recombinant proteins argue for keratin orthologs, but the sequences do not directly reveal which protein behaves as a keratin I or II ortholog. This problem is solved by the finding that keratin 8, a type II keratin from man or Xenopus, forms chimeric IF when mixed with Styela D. Mutant proteins of Styela D and keratin 8 with a single cysteine in equivalent positions show that these chimeric IF are, like vertebrate keratin filaments, based on the hetero coiled coil. We propose that Styela D retains, in spite of its strong sequence drift, important molecular features of type I keratins. By inference Styela C reflects a type II ortholog. We discuss that type I to III IF proteins are expressed along the chordate branch of metazoa.

Amino Acid Sequence↗