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Biomedical subjects

R Roth

Publications and source records attributed to R Roth.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Surgical treatment of injuries of the thoracolumbar transition--3: Follow-up examination. Results of a prospective multi-center study by the "Spinal" Study Group of the German Society of Trauma Surgery].

OBJECTIVES: Prospective, multicenter study addressing late results after operative treatment of acute thoracolumbar spinal injuries. METHODS: 682 patients (T10-L2) were included and 372 (80%) were postoperatively followed for 2 1/4 years (4-61 months). RESULTS: Comparing the initially included patients (n = 682) with the study group (n = 372), no differences were observed and results were assumed to be representative. A C-type lesion or polytrauma significantly prolonged the hospital stay. The method of operative treatment did not affect the length of the rehabilitation period. Neurological improvement was observed in 3 out of 7 patients with complete, and in 44 out of 64 (69%) with incomplete lesion. The operative method did not affect the improvement rate. The physical capacity significantly decreased. After a mean of 1/2 year of disability only 71% returned to work. 48% returned to their preoperative physical level. The mean Hannover Spine Score was 68 points (preoperative 94, p < 0.001), indicating permanent impairment of function. The angle-stable internal fixator was superior in restoration of spinal alignment and best radiological results were noted after combined stabilization. Posterior stabilization lead to high re-kyphosing. No correlations between radiologic and clinical parameters were observed. CONCLUSIONS: All treatment methods under study were appropriate for achieving comparable clinical and functional outcome. The internal fixator is superior in restoration of the spinal alignment. Best radiological outcome is achieved by combined stabilization. Merely by direct reconstruction of the anterior column the postoperative re-kyphosing is prevented and a gain in segmental angle is achieved.

Adolescent↗
PubMed2001

Plastids undifferentiated, a nuclear mutation that disrupts plastid differentiation in Zea mays L.

Photosynthetic development in any plant requires the intracellular co-ordination of chloroplast and nuclear gene expression programs. In this report, we investigate the role of a nuclear gene in photosynthetic development by examining C4 photosynthetic differentiation in a yellow mutant of maize (Zea mays L.). The plastids undifferentiated (pun) mutation disrupts plastid biogenesis in both bundle sheath and mesophyll cells, at an early developmental stage and in a light-independent manner. Chloroplast thylakoids are disrupted in the mutant and both membrane-associated and soluble chloroplast-encoded proteins accumulate at much reduced levels. The observed plastid morphology is consistent with a general defect in chloroplast biogenesis that is most likely exerted at the post-translational level. Despite aberrant chloroplast development, nuclear photosynthetic genes are expressed normally in pun mutants. Thus, neither functional chloroplasts nor the Pun gene product are required to establish nuclear photosynthetic gene expression patterns in maize.

Cell Nucleus↗
PubMed2001

Identification of distinct specificity determinants in resistance protein Cf-4 allows construction of a Cf-9 mutant that confers recognition of avirulence protein Avr4.

The tomato resistance genes Cf-4 and Cf-9 confer specific, hypersensitive response-associated recognition of Cladosporium carrying the avirulence genes Avr4 and Avr9, respectively. Cf-4 and Cf-9 encode type I transmembrane proteins with extracellular leucine-rich repeats (LRRs). Compared with Cf-9, Cf-4 lacks two LRRs and differs in 78 amino acid residues. To investigate the relevance of these differences for specificity, we exchanged domains between Cf-4 and Cf-9, and mutant constructs were tested for mediating the hypersensitive response by transient coexpression with either Avr4 or Avr9. We show that the number of LRRs is essential for both Cf-4 and Cf-9 function. In addition, Cf-9 specificity resides entirely in the LRR domain and appears to be distributed over several distant LRRs. In contrast, Cf-4 specificity determinants reside in the N-terminal LRR-flanking domain and three amino acid residues in LRRs 13, 14, and 16. These residues are present at putative solvent-exposed positions, and all are required for full Cf-4 function. Finally, we show that Cf-9 carrying the specificity determinants of Cf-4 has recognitional specificity for AVR4. The data indicate that diversifying selection of solvent-exposed residues has been a more important factor in the generation of Cf-4 specificity than has sequence exchange between Cf-4 progenitor genes. The fact that most variant residues in Cf-4 are not essential for Cf-4 specificity indicates that the diverse decoration of R proteins is not fully adapted to confer recognition of a certain avirulence determinant but likely provides a basis for a versatile, adaptive recognition system.

Amino Acid Sequence↗
PubMed2001

Psychological and ethical aspects of prevention trials.

Advances in immunological and genetic tests and in therapeutics may soon make it possible to predict, prevent or delay the development of type 1 diabetes mellitus (DM). Psychological support should be available at every stage of the screening and prevention process for high-risk individuals. Each step in this process results in a threat to the affected individual and his/her family, followed by anxiety, decision processes, uncertainty, conflicts and depression, and also attempts to cope with these. At the first step, information about the screening procedure is provided, and an attempt is made to motivate individuals and families to take part. At the second step, there is notification of risk and, for the small group of marker-positive individuals, an invitation to participate in a prevention trial. At the third step, the individuals included in a prevention protocol have to deal with anxiety over receiving placebo, maintain cooperation with therapy, and cope with potential failures of the prevention. There are only a few psychological data gained in DM screening or intervention studies, showing high clinical anxiety while screening, both before and after notification of risk. After a few months of anxiety, it usually drops to normal levels, but family functioning seems to be changed. Data are explained within the framework of an extended Health Belief Model. Data regarding the psychological impact on family members and identification of variables related to continued study participation are needed for studies seeking to recruit and retain subjects in longitudinal protocols for prediction and prevention of type 1 DM.

Clinical Trials as Topic↗
PubMed2000

New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis.

The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor induced angiogenesis. VEGF receptors, the tyrosine kinases Flt-1 and KDR, are expressed on vascular endothelial cells and initiate angiogenesis upon activation by VEGF. 1-Anilino-(4-pyridylmethyl)-phthalazines, such as CGP 79787D (or PTK787 / ZK222584), reversibly inhibit Flt-1 and KDR with IC(50) values < 0.1 microM. CGP 79787D also blocks the VEGF-induced receptor autophosphorylation in CHO cells ectopically expressing the KDR receptor (ED(50) = 34 nM). Modification of the 1-anilino moiety afforded derivatives with higher selectivity for the VEGF receptor tyrosine kinases Flt-1 and KDR compared to the related receptor tyrosine kinases PDGF-R and c-Kit. Since these 1-anilino-(4-pyridylmethyl)phthalazines are orally well absorbed, these compounds qualify for further profiling and as candidates for clinical evaluation.

Administration, Oral↗
PubMed2000

[Transoral correction osteotomy in transdental fracture dislocation that healed in the wrong position].

Undislocated odontoid fractures may lead on the basis of conventional x-rays only to a wrong conclusion with regard to biomechanical aspect of stability. In this aspect the classification based on Anderson and D'Alonzo takes a high risk to misunderstand the fracture stability and can results in a secondary fracture dislocation. Therefore it is important to make the decision about operative versus nonoperative treatment on the base of the trauma mechanism. In this case report we elucidate this problem and the higher risk of anterior approach for correction. Furthermore a better classification of dens fractures will be recommended.

Adult↗
PubMed2000

Isolated sixth nerve palsy: an uncommon presenting sign of multiple sclerosis.

We describe three patients in whom an isolated sixth nerve palsy was the only clinical symptom or sign of multiple sclerosis (MS). Data were collected prospectively over 6 years on these three patients, who showed no other signs of brainstem dysfunction or prior symptoms; in addition. Retrospective analysis of all patients with MS and all patients with sixth nerve palsy referred to a neuro-ophthalmology service between 1982 and 1998 showed isolated sixth nerve palsy to be the presenting sign of MS in only 0.5% of these patients. MS was the cause of isolated sixth nerve palsy in 0.8% of all patients and in 1.6% of those aged 18-50 years. Although it has been previously suggested that sixth nerve palsy is a not uncommon presenting sign of MS, our results suggest it is rare.

Abducens Nerve Diseases↗
PubMed2000

Actin assembly plays a variable, but not obligatory role in receptor-mediated endocytosis in mammalian cells.

Three cell-permeant compounds, cytochalasin D, latrunculin A and jasplakinolide, which perturb intracellular actin dynamics by distinct mechanisms, were used to probe the role of filamentous actin and actin assembly in clathrin-mediated endocytosis in mammalian cells. These compounds had variable effects on receptor-mediated endocytosis of transferrin that depended on both the cell line and the experimental protocol employed. Endocytosis in A431 cells assayed in suspension was inhibited by latrunculin A and jaspiakinolide, but resistant to cytochalasin D, whereas neither compound inhibited endocytosis in adherent A431 cells. In contrast, endocytosis in adherent CHO cells was more sensitive to disruption of the actin cytoskeleton than endocytosis in CHO cells grown or assayed in suspension. Endocytosis in other cell types, including nonadherent K562 human erythroleukemic cells or adherent Cos-7 cells was unaffected by disruption of the actin cytoskeleton. While it remains possible that actin filaments can play an accessory role in receptor-mediated endocytosis, these discordant results indicate that actin assembly does not play an obligatory role in endocytic coated vesicle formation in cultured mammalian cells.

Actins↗
PubMed2000

Coatomer vesicles are not required for inhibition of Golgi transport by G-protein activators.

The G-protein activators guanosine 5'-O-(3-thiodiphosphate) (GTP gamma S) and aluminum fluoride (AIF) are thought to inhibit transport between Golgi cisternae by causing the accumulation of nonfunctional coatomer-coated transport vesicles on the Golgi. Although GTP gamma S and AIF inhibit transport in cell-free intra-Golgi transport systems, blocking coatomer vesicle formation does not. We therefore determined whether inhibition of in vitro Golgi transport by these agents requires coatomer vesicle formation. Depletion of coatomer was found to completely block coated vesicle formation on Golgi cisternae without affecting inhibition of in vitro transport by either GTP gamma S or AIF. Depletion of ADP-ribosylation factor (ARF) prevented inhibition of transport by GTP gamma S, but not by AIF, suggesting that the AIF-sensitive component in transport may not be a GTP-binding protein. Surprisingly, depletion of cytosolic ARF did not prevent the GTP gamma S-induced formation of Golgi-coated vesicles, whereas ARF was required for AIF-induced vesicle formation. Although ARF or coatomer depletion caused an increase in the fenestration of cisternae, no other ultrastructural changes were observed that might explain the inhibition of transport by GTP gamma S or AIF. These findings suggest that ARF-GTP gamma S and AIF act by distinct and coatomer-independent mechanisms to inhibit membrane fusion in cell-free intra-Golgi transport.

ADP-Ribosylation Factors↗
PubMed2000

Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays.

We describe a novel sequencing approach that combines non-gel-based signature sequencing with in vitro cloning of millions of templates on separate 5 microm diameter microbeads. After constructing a microbead library of DNA templates by in vitro cloning, we assembled a planar array of a million template-containing microbeads in a flow cell at a density greater than 3x10(6) microbeads/cm2. Sequences of the free ends of the cloned templates on each microbead were then simultaneously analyzed using a fluorescence-based signature sequencing method that does not require DNA fragment separation. Signature sequences of 16-20 bases were obtained by repeated cycles of enzymatic cleavage with a type IIs restriction endonuclease, adaptor ligation, and sequence interrogation by encoded hybridization probes. The approach was validated by sequencing over 269,000 signatures from two cDNA libraries constructed from a fully sequenced strain of Saccharomyces cerevisiae, and by measuring gene expression levels in the human cell line THP-1. The approach provides an unprecedented depth of analysis permitting application of powerful statistical techniques for discovery of functional relationships among genes, whether known or unknown beforehand, or whether expressed at high or very low levels.

Cell Line↗
PubMed2000

[Reduction of the radiation exposure of patients caused by selected interventional and angiographic procedures].

PURPOSE: To reduce patient doses caused by selected interventional and angiographic procedures using the digital C-arm unit "Multiskop". MATERIALS AND METHODS: After a patient study done previously, physical measurements with test phantoms were carried out, and physical-technical parameters such as distance between focus and image intensifier, additional filtration, and radiation dose per image were optimised. Then, the dose-area product (DAP) and the fluoroscopic time were measured for 130 percutaneous transluminal angioplasties (PTA), 40 PTA with stent implantation, 61 embolisations, and 302 digital subtraction angiographies (DSA). In the case of 16 PTA, 9 embolisations, and 38 DSA the number of radiographs was determined, and the DAP was divided into two parts, fluoroscopy and radiography. The measuring values were compared with data of the patient study done previously. RESULTS: The median values of the DAP and the fluoroscopic time amounted to 25 Gy cm2 and 9.7 min for PTA, 97 Gy cm2 and 8.5 min for PTA with stent implantation, 88 Gy cm2 and 17.2 min for embolisation as well as 54 Gy cm2 and 2.8 min for DSA. For the relation between DAP caused by fluoroscopy and radiography, and the number of radiographs, median values of 0.76 and 63 for PTA, 0.81 and 123 for embolisation as well as 1.85 and 134 for DSA were determined. In comparison to the patient study done previously the median values of the DAP were reduced by 31% for PTA, 26% for PTA with stent implantation, 55% for embolisation, and 38% for DSA. CONCLUSIONS: The comparison between the patient studies done previously and recently indicates the great potential of dose reduction for interventional and angiographic procedures. Although the X-ray equipment is ten years old the patient dose can be reduced by organizational and physical-technical modifications to such an extent that preliminary national reference dose values will not be exceeded. For further significant dose reductions while maintaining adequate image quality it will be necessary to purchase a modern X-ray equipment with pulsed fluoroscopy and automatic filter selection.

Angiography↗
PubMed2000

Agroinfiltration is a versatile tool that facilitates comparative analyses of Avr9/Cf-9-induced and Avr4/Cf-4-induced necrosis.

The avirulence genes Avr9 and Avr4 from the fungal tomato pathogen Cladosporium fulvum encode extracellular proteins that elicit a hypersensitive response when injected into leaves of tomato plants carrying the matching resistance genes, Cf-9 and Cf-4, respectively. We successfully expressed both Avr9 and Avr4 genes in tobacco with the Agrobacterium tumefaciens transient transformation assay (agroinfiltration). In addition, we expressed the matching resistance genes, Cf-9 and Cf-4, through agroinfiltration. By combining transient Cf gene expression with either transgenic plants expressing one of the gene partners, Potato virus X (PVX)-mediated Avr gene expression, or elicitor injections, we demonstrated that agroinfiltration is a reliable and versatile tool to study Avr/Cf-mediated recognition. Significantly, agroinfiltration can be used to quantify and compare Avr/Cf-induced responses. Comparison of different Avr/Cf-interactions within one tobacco leaf showed that Avr9/Cf-9-induced necrosis developed slower than necrosis induced by Avr4/Cf-4. Quantitative analysis demonstrated that this temporal difference was due to a difference in Avr gene activities. Transient expression of matching Avr/Cf gene pairs in a number of plant families indicated that the signal transduction pathway required for Avr/Cf-induced responses is conserved within solanaceous species. Most non-solanaceous species did not develop specific Avr/Cf-induced responses. However, co-expression of the Avr4/Cf-4 gene pair in lettuce resulted in necrosis, providing the first proof that a resistance (R) gene can function in a different plant family.

Agrobacterium tumefaciens↗
PubMed2000

Depletion potential in hard-sphere mixtures: theory and applications

We present a versatile density functional approach (DFT) for calculating the depletion potential in general fluid mixtures. For the standard situation of a single big particle immersed in a sea of small particles near a fixed object, the system is regarded as an inhomogeneous binary mixture of big and small particles in the external field of the fixed object, and the limit of vanishing density of the big species, rho(b)-->0, is taken explicitly. In this limit our approach requires only the equilibrium density profile of a one-component fluid of small particles in the field of the fixed object, and a knowledge of the density independent weight functions which characterize the mixture functional. Thus, for a big particle near a planar wall or a cylinder or another fixed big particle, the relevant density profiles are functions of a single variable, which avoids the numerical complications inherent in brute force DFT. We implement our approach for additive hard-sphere mixtures, comparing our results with computer simulations for the depletion potential of a big sphere of radius R(b) in a sea of small spheres of radius R(s) near (i) a planar hard wall, and (ii) another big sphere. In both cases our results are accurate for size ratios s=R(s)/R(b) as small as 0.1, and for packing fractions of the small spheres eta(s) as large as 0.3; these are the most extreme situations for which reliable simulation data are currently available. Our approach satisfies several consistency requirements, and the resulting depletion potentials incorporate the correct damped oscillatory decay at large separations of the big particles or of the big particle and the wall. By investigating the depletion potential for high size asymmetries we assess the regime of validity of the well-known Derjaguin approximation for hard-sphere mixtures and argue that this fails, even for very small size ratios s, for all but the smallest values of eta(s) where the depletion potential reduces to the Asakura-Oosawa potential. We provide an accurate parametrization of the depletion potential in hard-sphere fluids, which should be useful for effective Hamiltonian studies of phase behavior and colloid structure. Our results for the depletion potential in a hard-sphere system, with a size ratio s=0.0755 chosen to mimic a recent experiment on a colloid-colloid mixture, are compared with the experimental data. Although there is good overall agreement, in particular for the dependence of the oscillations on eta(s), there are some significant differences at high values of eta(s).

Journal Article↗
PubMed2000

Binary hard-sphere fluids near a hard wall

By using the Rosenfeld density functional, we determine the number density profiles of both components of binary hard-sphere fluids close to a planar hard wall as well as the corresponding excess coverage and surface tension. The comparison with published simulation data demonstrates that the Rosenfeld functional, both its original version and sophistications thereof, is superior to previous approaches, and exhibits the same excellent accuracy as known from studies of the corresponding one-component system.

Journal Article↗