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Biomedical subjects

U Weber

Publications and source records attributed to U Weber.

At least 55 records · Page 3Linked to original sources
PubMed2000

Sequence and expression of the kettin gene in Drosophila melanogaster and Caenorhabditis elegans.

Kettin is a large modular protein associated with thin filaments in the Z-disc region of insect muscles. The sequence of a 21.3 kb contig of the Drosophila gene has been determined. The corresponding protein sequence has 35 immunoglobulin-like (Ig) domains which are separated by shorter linker sequences, except near the N and C termini of the molecule where linker sequences are short or missing. This confirms a model in which each Ig domain binds to an actin protomer. The Drosophila kettin gene is at 62C 1-3 on the third chromosome. Two P-element insertions, l(3)j1D7 and l(3)rL182 are in the kettin gene, and complementation tests showed that existing l(3)dre8 mutations are in the same gene. The RNA was detected in wild-type Drosophila embryos at stage 11, first in the gut invagination region of the mesoderm, and by stage 13 in both visceral and somatic mesoderm. Somatic mesoderm expression became segmental at stage 13. RNA expression was greatly reduced in embryos of P-element homozygotes but normal in heterozygotes. The structure of the flight muscle in all the heterozygous mutants was normal, including the myofibril-cuticle connections, and they were able to fly. Kettin sequence homologous to the Drosophila protein, was identified in the Caenorhabditis elegans genome database. The RNA was detected in pharyngeal, body wall and anal depressor muscles of larvae and adult worms, as well as in the male gonad. Antibody to insect kettin labelled the pharyngeal, body wall, anal depressor and proximal gonadal muscles in adult worms. Body wall muscles were labelled in an obliquely striated pattern consistent with the Z-disc localisation in insect muscle. The relationship of kettin to D-titin, which has been assigned to the same chromosomal locus in Drosophila, is discussed.

Amino Acid Sequence↗
PubMed2000

[Ventrodorsal correction and instrumentation in idiopathic scoliosis].

A number of different procedures are used for the surgical treatment of King II scoliosis. One reason for the controversial discussion in this context is that the term King II scoliosis is usually inadequate, because there are partly marked clinical and radiological differences in this type of curvature. From January 1996 to December 1997, a total of 26 patients with rigid King II scoliosis were submitted to a ventrodorsal procedure. Twenty-three patients were included in the study. The indication for this procedure was established in cases with a secondary lumbar curvature of at least 50 degrees as well as unsatisfactory straightening of the primary and secondary curvature in the bendings and inadequate horizontal positioning of the caudal end vertebra of not less than 10 degrees. Ventral Derotation-Spondylodesis (VDS) and Dorsal correction-Spondylodesis (DKS) led to a thoracic and lumbar straightening from 68.4 degrees to 13.2 degrees and from 61.4 degrees to 17.8 degrees, respectively. The tilt of the vertebra instrumented farthest caudally was corrected from 21.2 degrees to 4.9 degrees. The thoracic hypokyphosis was improved from 16.6 degrees to 25.1 degrees. In 11 patients, the dorsal instrumentation was extended to the caudal end vertebra, in another 11 patients, instrumentation was achieved up to a vertebra cranial from the end vertebra. The correction loss and complication rate was extremely low. Based on the surgical goals discussed further down, combined application of VDS and DKS is efficient and suitable in conjunction with the indication described. The complication rate is quite low. The different types of King II scoliosis have to be differentiated preoperatively.

Adolescent↗
PubMed2000

CT and MRI in severe hypophosphataemia with central nervous system involvement.

We report a 38-year-old woman with extreme hypophosphataemia in whom CT and MRI disclosed bilateral lesions within the basal ganglia, thalamus and occipital lobes. After adequate substitution of phosphate the lesions grossly resolved and the patient recovered. This case is the first to demonstrate that profound changes of serum phosphate may be associated with reversible brain lesions.

Adult↗
PubMed2000

[Assessment of routine mobility in geriatrics using static posturography--a population based study].

In a population-based study of 110 women between 53 and 82 years of age (mean age 64.5 +/- 7.9 years) static posturography data were compared to functional items of gait and balance in common geriatric mobility scales. Posturographic data of double-stance with eyes open and eyes closed (DSEO; DSEC) did not differ from those of a group of healthy women previously tested for intact nervous system function. The total neuromuscular score--roughly corresponding to the well-known Tinetti score--did not correlate to the posturographic measures. DSEC correlated with the items "rapid walking" and "single-stance left leg". Age, vision, and neuropsychologic test results correlated with DSEO, "rapid walking", "single-stance right leg", "single-stance left leg", and "walking a figure eight". Multiple linear regression confirmed the impact of age, vision, DSEO, and DSEC on "rapid walking" with a 34% variance explanation. Posturographic parameters did predict other selected gait and balance items. When used in older women living independently in the community, parameters of static posturography reflect to some extent the functional disabilities of gait and balance.

Activities of Daily Living↗
PubMed2000

Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial.

AIMS: 5-hydroxytryptamine3 receptor antagonists act antiemetically and slow colonic transit. This study evaluated effects of the high-affinity 5-HT3 antagonist, cilansetron, on fasting, meal-and anticholinesterase-stimulated phasic contractile activity of the human sigmoid colon as well as on bowel habits and stool consistency. METHODS: Five female and seven male healthy volunteers received, during three 7 day periods separated by 7 day wash-out periods, 4 mg cilansetron, 8 mg cilansetron or placebo three times daily orally under random, double-blind, crossover conditions. On day 8 of each treatment period, motility 20-40 cm from the anal verge was recorded using five pressure sensors spaced at 5 cm intervals. After a basal 30 min, subjects swallowed a further dose of the scheduled treatment; 60 min later, blood was taken for the determination of plasma cilansetron levels. Thereafter, subjects ingested a 4200 kJ meal and 250 ml sweetened mallow tea (166 kJ); 90 min after meal onset, 1 mg neostigmine was administered intramuscularly and motility recording was continued for 60 min RESULTS: Phasic contractile activity and intraluminal base-line pressure increased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the number of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not affected. The effects of the two cilansetron dosages did not differ. With cilansetron, stool tended to become firmer. No adverse effects were observed. Plasma levels were highest with 8 mg cilansetron. CONCLUSIONS: Cilansetron slightly augments meal-stimulated and markedly neostigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.

Adult↗
PubMed2000

Treatment planning for heavy-ion radiotherapy: physical beam model and dose optimization.

We describe a novel code system, TRiP, dedicated to the planning of radiotherapy with energetic ions, in particular 12C. The software is designed to cooperate with three-dimensional active dose shaping devices like the GSI raster scan system. This unique beam delivery system allows us to select any combination from a list of 253 individual beam energies, 7 different beam spot sizes and 15 intensity levels. The software includes a beam model adapted to and verified for carbon ions. Inverse planning techniques are implemented in order to obtain a uniform target dose distribution from clinical input data, i.e. CT images and patient contours. This implies the automatic generation of intensity modulated fields of heavy ions with as many as 40000 raster points, where each point corresponds to a specific beam position, energy and particle fluence. This set of data is directly passed to the beam delivery and control system. The treatment planning code has been in clinical use since the start of the GSI pilot project in December 1997. Forty-eight patients have been successfully planned and treated.

Algorithms↗
PubMed2000

Depth scanning for a conformal ion beam treatment of deep seated tumours.

Only target-conformal treatment allows one to exploit the advantages of ion beams (the increased dose and high biological efficiency at the end of the particle range) to a maximum extent. Up to now, target-conformal treatments such as spot scanning or intensity-controlled raster scanning have used fast magnetic lateral deflection in one or two directions perpendicular to the beam axis and a slow range variation in the longitudinal axis by active or passive energy variation. The present paper describes a new method for conformal irradiation with a fast intensity-controlled longitudinal scan in the beam direction, called 'depth scanning'. Its advantages and disadvantages will be discussed. First experimental results from depth scanning will be presented.

Dose-Response Relationship, Radiation↗
PubMed2000

Three-dimensional BANG gel dosimetry in conformal carbon ion radiotherapy.

In this study we applied BANG polymer-gel dosimetry using magnetic resonance imaging (MRI) to densely ionizing radiation such as carbon ion beams. BANG polymer gels were irradiated with a quadratic field of monoenergetic 12C ions at different beam energies in the range of 135 MeV u(-1) to 410 MeV u(-1). They were irradiated at the radiotherapy facility of the GSI, Darmstadt, Germany. Our object was to examine the saturation effect for densely ionizing radiation that occurs at high values of linear energy transfer (LET). The examination yielded the first effectiveness values that will be discussed in the following sections. A solid sphere and a hollow sphere were both irradiated with a horizontal pencil beam from the raster scanning facility at energies of 268 MeV u(-1) (solid sphere) and 304 MeV u(-1) (hollow sphere) respectively. MR dosimetry measurements were compared with data from a planning system. As far as quality is concerned, there is good agreement between the measured dose distributions of both samples and the dose maps from the planning software. The measured MR signals cannot be converted into absolute dose, since the relative efficiency is still unknown for mixed radiation fields of primary carbon ions and it is known only to a limited extent for nuclear fragments with different energies from highly energetic photon radiation. Model calculations are in progress in order to facilitate conversions of measured MR signals into dose.

Acrylamides↗
PubMed2000

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: A case-control study: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke. METHODS: We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the "forced air" method, a surface cooling method that uses a cooling blanket with a flow of cool air (10 degrees C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy. RESULTS: Body temperature decreased from t(0)=36.8 degrees C to t(6)=35.5 degrees C (P:<0.001), and hypothermia was present until 4 hours after therapy (t(0)=36.8 degrees C versus t(10)=36.5 degrees C; P:=0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls (P:=0. 50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls (P:=0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses. CONCLUSIONS: Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the "forced air" method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke.

Acute Disease↗
PubMed2000

Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye.

Jun acts as a signal-regulated transcription factor in many cellular decisions, ranging from stress response to proliferation control and cell fate induction. Genetic interaction studies have suggested that Jun and JNK signaling are involved in Frizzled (Fz)-mediated planar polarity generation in the Drosophila eye. However, simple loss-of-function analysis of JNK signaling components did not show comparable planar polarity defects. To address the role of Jun and JNK in Fz signaling, we have used a combination of loss- and gain-of-function studies. Like Fz, Jun affects the bias between the R3/R4 photoreceptor pair that is critical for ommatidial polarity establishment. Detailed analysis of jun(-) clones reveals defects in R3 induction and planar polarity determination, whereas gain of Jun function induces the R3 fate and associated polarity phenotypes. We find also that affecting the levels of JNK signaling by either reduction or overexpression leads to planar polarity defects. Similarly, hypomorphic allelic combinations and overexpression of the negative JNK regulator Puckered causes planar polarity eye phenotypes, establishing that JNK acts in planar polarity signaling. The observation that Dl transcription in the early R3/R4 precursor cells is deregulated by Jun or Hep/JNKK activation, reminiscent of the effects seen with Fz overexpression, suggests that Jun is one of the transcription factors that mediates the effects of fz in planar polarity generation.

Animals↗
PubMed2000

Changes in the loads on an internal spinal fixator after iliac-crest autograft.

Spines are often stabilised posteriorly by internal fixation and anteriorly by a bone graft. The effect of an autologous bone graft from the iliac crest on implant loads is unknown. We used an internal spinal fixation device with telemetry to measure implant loads for several body positions and activities in nine patients before and after anterior interbody fusion. With the body upright, implant loads were often higher after than before fusion using a bone graft. Distraction of the bridged region led to high implant loads in patients with a fractured vertebra and to marked changes in load in those with degenerative instability. Leaving the lower of the bridged intervertebral discs intact led to only small changes in fixator load after anterior interbody fusion. A bone graft alone does not guarantee a reduction of implant loads.

Adult↗
PubMed1999

Internal spinal fixator stiffness has only a minor influence on stresses in the adjacent discs.

STUDY DESIGN: Stresses in vertebral endplates and discs were calculated using the three-dimensional nonlinear finite-element model of a lumbar spine with an internal spinal fixation device. OBJECTIVE: To determine the influence of fixator stiffness on stresses in the adjacent discs. SUMMARY OF BACKGROUND DATA: There are few computer models of the lumbar spine with a fixator. Most of these models neglect the muscle forces. Fixator stiffness is assumed to influence greatly the stresses in the adjacent discs. METHODS: Two three-dimensional nonlinear finite-element models were used to determine stresses in the lumbar spine for standing and 60 degrees flexion of the upper body. One model had an internal spinal fixator, the other did not. In a parameter study, the diameters of the longitudinal rod of the fixator were assumed to be 3, 5, 7, and 10 mm. In the computer model, the forces of the trunk muscles were simulated. RESULTS: The diameter of the longitudinal rod strongly affected the fixator loads but hardly influenced the stresses in the vertebral endplates. The stresses in the bridged discs were strongly reduced. However, the internal fixator had only a minor influence on the stresses in the anulus fibrosus and the pressure in the nucleus pulposus of the adjacent discs. CONCLUSIONS: The stiffness of an internal spinal fixation device has only a minor influence on stresses in the adjacent discs.

Elasticity↗
PubMed1999

Glucocorticoids differentially control synthesis of acetylcholinesterase and butyrylcholinesterase in rat liver and brain.

Mammalian organisms possess two cholinesterases: acetylcholinesterase (AChE, EC 3.1.1.7.) and butyrylcholinesterase (BuChE, EC 3.1.1.8.). A clear explanation for this dual expression of acetylcholine-hydrolyzing enzymes is still missing. Better knowledge on how these two enzymes respond to various physiological or pharmacological factors would importantly contribute to the understanding of their function. The aim of the present study is to elucidate glucocorticoid (GC) influences on the synthesis of AChE and BuChE in rat liver and brain. Female Wistar rats were treated with dexamethasone until body weight loss was greater than 15%, signaling full expression of a GC response. At this stage, liver and brain were isolated and AChE and BuChE activities were determined in their homogenates. A new approach, based on precise radiometric measurements of AChE and BuChE activities in the polysomal fractions, prepared under non-denaturing conditions, was used to study GC influences on the early stages of biosynthesis of both enzymes. We found a differential GC influence on AChE and BuChE. In brain, only BuChE activity was affected (-30%), while AChE remained practically unchanged. In liver, BuChE activity fell by 60%, while AChE lost only 18% of its control activity. In case of BuChE, decreased activities in the whole homogenates correlated with decreased activities in the polysomal fractions, suggesting that early stages of enzyme biosynthesis were primarily affected. On the other hand, decreased AChE activity in liver homogenates was not paralleled by a significant change at the level of polysomal AChE activity in this organ, suggesting that higher AChE turn-over is primarily responsible for the decreased activity in homogenate. These results, together with the GC-mediated elimination of the correlation between brain and liver BuChE activities, strongly support the proposal of Edwards and Brimijoin (J.A. Edwards, S. Brimijoin, Effects of hypophysectomy on acetylcholinesterase and butyrylcholinesterase in the rat, Biochem. Pharmacol. 32 (1983) 1183-1189) that BuChE is regulated by systemically acting factors, including various hormones, while regulation of AChE is primarily tissue-specific.

Acetylcholinesterase↗
PubMed1999

[Fractures of the distal radius. Changing therapeutic strategies].

Fractures of the distal radius represent one of the most common fractures and do have high social-economic relevance. For treatment they need practicable classification and therapeutic standards. The demand for stable osteosynthesis of A3-, B2-B3 and C1-C2-fractures is connected to dorsal or volar internal fixation with plate and practical autogenous cancellous bone grafting, even for the elder patient. The isolated external fixation with K-wires represent special situation. Supply of implants and biodegradable materials will support this development.

Absorbable Implants↗
PubMed1999

[Scaphoid fracture and scaphoid pseudarthrosis].

Careful diagnostic and early therapy are especially important in cases of scaphoid fractures. This is due to the patients being mostly young and the high number of non-unions of these carpal bones. Conservative and various operative treatments are therapeutical options. Out of the patients who underwent surgery from January 1993 to February 1999 42 patients with a scaphoid fracture and 88 patients with a scaphoid non-union were, in addition to standard X-ray examination, examined clinically and by MRI pre- and post-operatively. Fractures of the scaphoid were treated by Herbert screw fixation. The operative treatment of non-unions of the scaphoid included the transplantation of an iliac crest graft and Herbert screw fixation. Post-operatively a cast-immobilisation was done. Subjective statements of the patients and clinical results were assessed. The classification of Herbert and Fisher (1984)/Filan and Herbert (1996) for X-rays was used. The signal intensities of the MRI in the fragments of the scaphoid were determined qualitatively and quantitatively by computer calculation, comparing the pre- and post-operative results with one another. Post-operative results of the scaphoid fractures were in most cases good and excellent. 67 patients with a scaphoid non-union and 11 with a scaphoid fracture showed a pre-operative diminishing of the signal in the proximal fragment. For these patients, the fusion rate was lower than in patients without pre-operative signal reduction. The examination shows that in most cases bony fusions with good clinical results could be achieved by Herbert screw fixation. The MRI seems to be able to complete the radiological classification of the fractures regarding a prognosis.

Bone Screws↗
PubMed1999

[Ion transport in nasal and paranasal sinus mucosa in mucoviscidosis and chronic sinusitis].

Cystic fibrosis (CF) is the most commonly inherited disease in Caucasians and is caused by a mutation in the gene encoding a membrane transport protein. This cystic fibrosis transmembrane conductance regulator (CFTR) is thought to be an apical Cl- channel activated by intracellular cAMP. Most recent findings suggest that CFTR is more than a pure Cl- channel and might be involved in the regulation of other transport systems. In the present study we show that CFTR as a Cl- channel plays only a minor role in primary cultured human nasal epithelium derived from non-CF and CF patients. These findings are especially of interest for non-CF human nasal epithelia in which CFTR is correctly inserted. In both tissues Cl- secretion is negligible as compared with Na+ absorption. We confirm and expand our previous observations that Na+ absorption in human nasal epithelium is the dominant ion transport process and that Cl- secretion is detectable in both CF and non-CF tissue. Moreover, we show that cAMP and ATP were not able to stimulate any silent Cl- channels in CF or non-CF human nasal epithelial cells. We further give evidence that in human nasal CF and non-CF epithelium Na+ absorption is mediated by epithelial Na+ channels (ENaC) that are either different from those of other epithelia or which exhibit altered regulation. These differences between Na+ channels of human nasal epithelium and "classical" epithelial Na+ channels include lack of activation by the intracellular second messenger cAMP and the steroid hormone aldosterone. We show further that human nasal Na+ channels are inhibited by Cl- channel blockers and exhibit a different pharmacology towards common Na+ channel blockers.

Chloride Channels↗