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Biomedical subjects

I Hofmann

Publications and source records attributed to I Hofmann.

At least 19 recordsLinked to original sources

[Percutaneous endovascular aneurysm repair without arteriotomy (Perclose system)].

BACKGROUND AND OBJECTIVE: It is common clinical practice to perform an arteriotomy for the endovascular treatment of infrarenal and thoracic aortic aneurysms. Instead we used the percutaneous endovascular Perclose device to perform the aneurysm repair without arterial cut-down. PATIENTS AND METHODS: The Perclose device contains four needles with two suture loops for closing the femoral artery access site. The sutures were deployed after the arterial puncture, before introduction of sheaths (diameter 12 - 27 F = 4 - 9 mm). After the procedure the sutures were used to close the puncture site. We attempted to achieve hemostasis with the Perclose system in 104 femoral arteries in 60 patients (7 females, mean age 69 +/- 12 years). The mean vessel diameter was 10 +/- 2 mm. RESULTS: The percutaneous graft implantation was successfully achieved in 58 of 60 patients. The graft could not be forwarded into the aorta in two cases because of calcified iliac arteries. The Perclose suture technique was successfully used in 97 femoral arteries. In one case a false aneurysm developed and in another case a secondary hemorrhage occurred. Seven patients needed additional manual compression to achieve complete hemostasis. A surgical repair was not necessary. The time to hospital discharge ranged from 4.5 hours to 32 days (median: 18 hours). 20 patients stayed longer than 24 h in the hospital, only 2 of them for reasons related to the puncture site. CONCLUSION: Closing the access site with the Perclose system is technically feasible and effective, even with large sheaths up to 27 F = 9 mm. This technique reduces the invasiveness of the endovascular repair of aortic aneurysms and decreases the length of hospital stay, i. e. it allows treatment in outpatients.

Adult↗

Collective emittance exchange with linear space charge forces and linear coupling.

We show that pronounced collective nonlinear behavior is present in a beam with linear coupling and space charge as described by the complete second order moment equations. The collective effects result in a shifted and broadened resonance condition as well as saturation effects in the emittance transfer. For slow stop-band crossing either the beam evolves along a skewed matched solution with full emittance exchange or the exchange is hindered by collective space charge effects, depending on the emittance ratio and direction of crossing.

Journal Article↗

Anisotropic free-energy limit of halos in high-intensity accelerators.

We study halo emittance growth in anisotropic beams and show that the rms emittance growth resulting from mismatch is highly anisotropic, depending on the tune ratio. We find that the free-energy limit calculated by Reiser [J. Appl. Phys. 70, 1919 (1991)] for an axisymmetric 1D halo can be extended to 2D if understood as an upper bound to the rms emittance growth averaged per degree of freedom. The thus-obtained "free-energy limit" of an ideal transport system is compared with the halo rms emittance growth in simulations of the Spallation Neutron Source linac.

Journal Article↗

[Acute peripheral vestibular lesions. Monocular subjective visual vertical and cyclodeviation].

BACKGROUND: A deviation of the subjective visual vertical (svv) is often found in patients with unilateral peripheral vestibular lesions and in most cases the deviation is transitory and easy to compensate. The purpose of the study was to find out if there is a correlation between deviation of the svv and objective cyclodeviation of the retina. PATIENTS AND METHODS: A total of 20 patients (10 females and 10 males aged between 16 and 78 years) with acute vestibular disease were enrolled. Only patients with a binocular deviation of the svv of more than 2 degrees and/or a difference between the monocular deviation of more than 1.5 degrees were included. The svv was examined monocular in a darkened room and after pupil dilatation, fundus photography was performed on each eye. The angle between papilla and macula was measured manually. RESULTS: We found a good qualitative correlation between svv (mean 7.9 degrees) and objective cyclodeviation (mean 10.6 degrees). CONCLUSION: In contrast to the binocular measurement of the svv, we found good correlation between the monocular svv and the objective cyclorotation measured with fundus photography. It is not yet clear which part of the vestibular system is responsible for cyclodeviation. Because of our results we recommend monocular measurement of the svv in clinical examinations.

Adolescent↗

Resonant emittance transfer driven by space charge.

Space charge can lead to emittance and/or energy exchange known as "equipartitioning issue" in linacs, or space-charge coupling in high-current synchrotrons. It is described here as an internal resonance driven by the self-consistent space-charge potential of coherent eigenmodes. By a detailed comparison of analytical theory with 2D particle-in-cell simulation for Kapchinskij-Vladimirskij (KV) and waterbag distributions, we discuss characteristic features of this resonance mechanism in the vicinity of the symmetric focusing resonance band--for practical purposes, the most important case--and discuss the applicability of the linearized KV theory.

Journal Article↗

Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2.

Plakophilin 2, a member of the arm-repeat protein family, is a dual location protein that occurs both in the cytoplasmic plaques of desmosomes as an architectural component and in an extractable form in the nucleoplasm. Here we report the existence of two nuclear particles containing plakophilin 2 and the largest subunit of RNA polymerase (pol) III (RPC155), both of which colocalize and are coimmunoselected with other pol III subunits and with the transcription factor TFIIIB. We also show that plakophilin 2 is present in the pol III holoenzyme, but not the core complex, and that it binds specifically to RPC155 in vitro. We propose the existence of diverse nuclear particles in which proteins known as plaque proteins of intercellular junctions are complexed with specific nuclear proteins.

Animals↗

Collective resonance model of energy exchange in 3D nonequipartitioned beams.

Energy exchange between the longitudinal and transverse degrees of freedom of nonequipartitioned bunched beams (non-neutral plasmas) is investigated by means of 3D simulation. It is found that collective instability may lead to energy transfer in the direction of equipartition, without full progression to it, in certain bounded regions of parameter space where internal resonance conditions are satisfied, in good agreement with stability charts from an earlier derived 2D Vlasov analysis. Nonequipartitioned stable equilibria, however, exist in relatively wide regimes of parameter space. This provides evidence that such regimes may be safely used in the design of future high-intensity linacs.

Journal Article↗

Analytical calculation of the longitudinal space charge and resistive wall impedances in a smooth cylindrical pipe.

The longitudinal space charge and resistive wall impedances have been investigated in a smooth cylindrical beam pipe. At any point from the beam axis, we obtained an expression for the total impedance, which at the beam surface r=a for infinite pipe wall conductivity gives the expression for the total impedance that was derived by Zotter and Kheifets in studying the impedance of uniform beams in concentric cylindrical wall chambers, when a single cylindrical chamber is considered [B. W. Zotter and S. A. Kheifets, Impedances and Wakes in High-Energy Particle Accelerators (World Scientific, Singapore, 1998), Chap. 6]. A fitting formula for the space-charge impedance at the beam surface (r=a), which is valid for arbitrary wavelengths, is given. Rather than calculating the impedance with the field on the axis [Joseph J. Bisognano, Fifth European Particle Accelerator Conference (EPAC96), edited by S. Myers, A. Pacheco, R. Pascual, Ch. Petit-Jean-Genaz, and J. Poole (Institute of Physics, Bristol, 1996), Vol. 1, p. 328], the fitting formula is obtained by averaging over the transverse beam distribution. We also give another approach for the calculation of the resistive wall impedance using the flux of the Poynting vector at the pipe wall and then compare it with the expression obtained from the volume integral over the beam distribution.

Journal Article↗

[Difficulties in interprofessional dialogue between medical and nursing colleagues].

A dignified care of sick, old and impaired human beings requires intensive collaborations of medical and nursing staff. In order to prevent incomplete pain management, long hospitalisations, neglect of the dying, unnecessary transfers between nursing homes and hospitals partnership and dialogue between these two disciplines is necessary. In spite of this it seems to be the exception rather than the rule. Apart from hierarchical thinking and personal preferences structural conditions play an important part. This paper tries to relate various aspects: not all these can be supported by valid data (because of lacking research) but they are based on reflective practice. This article does not pretend to be a scientific piece of work. Nevertheless, it is hoped that it contributes to the improvement of the interdisciplinary dialogue. Enhanced research interest may be an additional effect of it.

Adult↗

Drebrin particles: components in the ensemble of proteins regulating actin dynamics of lamellipodia and filopodia.

Drebrin, an actin-binding 70-kDa protein with an unusually slow SDS-PAGE mobility corresponding to approximately 120 kDa, containing a proline-rich, profilin-binding motif, had originally been reported from neuronal cells, but recently has also been found in diverse other kinds of tissues and cell lines. In biochemical analyses of various cells and tissues, employing gel filtration, sucrose gradient centrifugation, immunoprecipitation and -blotting, we have identified distinct states of soluble drebrin: a approximately 4S monomer, an 8S, ca. 217-kDa putative trimer, a 13S and a > 20S oligomer. In the 8S particles only [35S]methionine-labelled drebrin but no other actin-binding protein has been detected in stoichiometric amounts. By immunofluorescence and immunoelectron microscopy, drebrin-positive material often appeared as "granules" up to 400 nm in diameter, in some cell types clustered near the Golgi apparatus or in lamellipodia, particularly at leading edges, or in dense-packed submembranous masses at tips (acropodia) or ruffles of leading edges, in filopodia and at plaques of adhering junctions. We conclude that these drebrin complexes and drebrin-rich structures allow the build-up and maintenance of high local drebrin concentrations in strategic positions for the regulation of actin filament assembly, thereby contributing to cell motility and morphology, in particular local changes of plasticity and the formation of protrusions.

Actins↗

Antibodies anti-Chlamydia pneumoniae and anti-Mycoplasma pneumoniae in patients with negative serology for hantavirus. Retrospective study.

The seroprevalence of Chlamydia pneumoniae and Mycoplasma pneumoniae in hantavirus seronegative patients, who had symptoms and signs compatible with pneumonia was established. For this purpose we used the indirect fluorescent antibody test. Titers > or = 1:16 for C. pneumoniae and M. pneumoniae were found in 8.6% and 17.1% of the serum, respectively, showing evidence of recent or current infection.

Adolescent↗

Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model.

Antiangiogenic therapy is a promising new strategy to inhibit tumor growth and formation of metastases. Vascular endothelial growth factor (VEGF) and its receptors, VEGF-receptor 1 (VEGF-R1; FLT-1) and VEGF-R2 (KDR), have been shown to play a major role in tumor angiogenesis. PTK787/ZK 222584, a specific inhibitor of both VEGF-receptor tyrosine kinases, was investigated for its antitumoral and antiangiogenic activity in a murine renal cell carcinoma model. After intrarenal application of the renal carcinoma cells, mice develop a primary tumor and metastases to the lung and to the abdominal lymph nodes. Daily oral therapy with PTK787/ZK 222584 at a dose of 50 mg/kg resulted in a significant decrease of 61 and 67% in primary tumors after 14 and 21 days, respectively. The occurrence of lung metastases was significantly inhibited at both time points (98% reduction and 78% reduction, respectively). After 14 days, no lymph node metastases developed in the PTK787/ZK 222584-treated group, whereas after 21 days of treatment, the lymph node metastases were reduced by 87%. Vessel density in tumor tissues, detected by immunohistochemistry with an anti-CD31 antibody, was significantly decreased by PTK787/ZK 222584. Using color Doppler imaging ultrasound, significant changes in blood flow in the tumor feeding renal artery were found under treatment with PTK787/ZK 222584. Blood flow changes correlated with changes in vessel density but not with tumor volume. The compound was well tolerated in all in vivo experiments and had no significant effects on body weight or general well-being of the animals. This was in contrast to the animals treated with the antiangiogenic agent TNP-470. s.c. therapy with 30 mg/kg TNP-470 every other day had to be discontinued after 13 days because of animal weight loss (>20%) and ataxia. These results demonstrate that PTK787/ZK 222584 is a potent inhibitor of tumor growth, metastases formation, and tumor vascularization in murine renal cell carcinoma. Furthermore, we have been able to demonstrate that color Doppler imaging ultrasound can be used to measure blood flow to a tumor and that flow correlates with vessel density. Thus, this may be a valuable noninvasive method for monitoring the effects of antiangiogenic agents such as PTK787/ZK 222584 on tumor vasculature.

Angiogenesis Inhibitors↗

Physical characterization of plakophilin 1 reconstituted with and without zinc.

Plakophilin 1 (PKP1) belongs to the arm-repeat protein family which is characterized by the presence of a conserved 42-amino-acid motif. Despite individual members of the family containing a similar type of structural domain, they exhibit diverse cellular functions. PKP1 is ubiquitously expressed in human tissues and, depending on the type of cell, found prominently in the karyoplasm and/or in desmosomes. In surface plasmon resonance detection experiments, we noticed that PKP1 specifically bound zinc but not calcium or magnesium. Therefore we have used circular dichroism spectroscopy, limited proteolysis, analytical ultracentrifugation, electron microscopy and dynamic light scattering to establish the physical properties of recombinant PKP1 depending on the presence or absence of zinc. The alpha helix content of PKP1 was considerably higher when reconstituted with zinc than without. By atomic absorption spectroscopy 7.3 atoms zinc were shown to be tightly associated with one molecule of wild-type PKP1. The zinc-reconstituted protein formed globular particles of 21.9 +/- 8.4 nm diameter, as measured by electron microscopy after glycerol spraying/rotary metal shadowing. In parallel, the average sedimentation coefficient (s20, w) for zinc-containing PKP1 was 41S and its diffusion coefficient, as obtained by dynamic light scattering, 1.48 x 10-7 cm2.s-1. The molecular mass of 2.44 x 106 obtained from s and D yields an average stoichiometry of 30 for the PKP1 oligomer. In contrast, PKP1, reconstituted without zinc, contained no significant amount of zinc, sedimented with 4.6S, and was present in monomeric form as determined by sedimentation equilibrium centrifugation.

Circular Dichroism↗

Interaction of plakophilins with desmoplakin and intermediate filament proteins: an in vitro analysis.

Plakophilin 1 and 2 (PKP1, PKP2) are members of the arm-repeat protein family. They are both constitutively expressed in most vertebrate cells, in two splice forms named a and b, and display a remarkable dual location: they occur in the nuclei of cells and, in epithelial cells, at the plasma membrane within the desmosomal plaques. We have shown by solid phase-binding assays that both PKP1a and PKP2a bind to intermediate filament (IF) proteins, in particular to cytokeratins (CKs) from epidermal as well as simple epithelial cells and, to some extent, to vimentin. In line with this we show that recombinant PKP1a binds strongly to IFs assembled in vitro from CKs 8/18, 5/14, vimentin or desmin and integrates them into thick (up to 120 nm in diameter) IF bundles extending for several microm. The basic amino-terminal, non-arm-repeat domain of PKP1a is necessary and sufficient for this specific interaction as shown by blot overlay and centrifugation experiments. In particular, the binding of PKP1a to IF proteins is saturable at an approximately equimolar ratio. In extracts from HaCaT cells, distinct soluble complexes containing PKP1a and desmoplakin I (DPI) have been identified by co-immunoprecipitation and sucrose density fractionation. The significance of these interactions of PKP1a with IF proteins on the one hand and desmoplakin on the other is discussed in relation to the fact that PKP1a is not bound - and does not bind - to extended IFs in vivo. We postulate that (1) effective cellular regulatory mechanisms exist that prevent plakophilins from unscheduled IF-binding, and (2) specific desmoplakin interactions with either PKP1, PKP2 or PKP3, or combinations thereof, are involved in the selective recruitment of plakophilins to the desmosomal plaques.

Cell Extracts↗

Angle-supported refractive implantation in stable, adult accommodative esotropia.

A patient with hyperopia and accommodative esotropia was implanted bilaterally with hyperopic angle-supported refractive implants. Control of the esotropia was achieved as was some improvement in fusional ability. After three years, the endothelium remains healthy, the eye is quiet and control of the esotropia is maintained.

Accommodation, Ocular↗

A splice site mutation in the gene of the human type I hair keratin hHa1 results in the expression of a tailless keratin isoform.

In this study, we have elucidated the molecular mechanisms underlying the expression of an acidic 41-kDa protein inherited as an autosomal dominant trait of the hair keratin pattern of about 5% of the human population. We show that this protein is a size variant of the large type I hair cortex keratin hHa1 due to a genetic polymorphism in the hHa1 gene. We detected a G-A substitution in the 5' splice site of intron 6 of the hHa1 gene, which segregates with the 41-kDa protein phenotype in two pedigrees and is responsible for the formation of an abnormally spliced hHa1 mRNA species. The use of an alternative 5' splice site leads to the retention of 41 nucleotides of the initial intron 6 sequences in the mature transcript. The open reading frame of the aberrant mRNA creates a premature stop codon immediately downstream of the mutation site. The resulting hHa1 protein variant, hHa1-t, is about 6-kDa smaller than the 47-kDa hHa1 hair keratin and lacks the complete nonhelical tail domain. We show that the tailless hHa1-t is functional, since both recombinant hHa1 and hHa1-t form identical keratin intermediate filaments when assembled in vitro with a type II hair keratin partner. This finding confirms the view of a noninvolvement of the keratin tail domain in filament assembly and explains the lack of a pathological hair phenotype in hHa1-t positive individuals.

Base Sequence↗