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Biomedical subjects

C Hofmann

Publications and source records attributed to C Hofmann.

At least 19 recordsLinked to original sources
PubMed2007

Plasmodesmata and intercellular transport of viral RNA.

Cell-to-cell communication in plants involves the symplastic trafficking of informational protein and RNA macromolecules through cytoplasmic bridges in the plant cell wall known as plasmodesmata. Viruses exploit this route for the spread of infection and are used as a model to study the mechanisms by which macromolecules are targeted to the pore. Studies using tobacco mosaic virus have led to the identification of host components that participate in plasmodesmal targeting of viral RNA and movement protein.

Cell Communication↗
PubMed2006

Spin-coated polyethylene films probed by single molecules.

We have studied ultrathin spin-coated high-density polyethylene films by means of single-molecule spectroscopy and microscopy at 1.8 K. The films have been doped with 2.3,8.9-dibenzanthanthrene (DBATT) molecules, which function as local reporters of their immediate environment. The orientation distributions of single DBATT probe molecules in 100-200 nm thin films of high-density polyethylene differ markedly from those in low-density films. We have found a preferential orientation of dopant molecules along two well-defined, mutually perpendicular directions. These directions are preserved over at least a 2 mm distance. The strong orientation preference of the probe molecules requires the presence of abundant lateral crystal faces and is therefore not consistent with a spherulitic morphology. Instead, a "shish-kebab" crystal structure is invoked to explain our results.

Journal Article↗
PubMed2006

Coherent photonic coupling of semiconductor quantum dots.

We report a new type of coupling between quantum dot excitons mediated by the strong single-photon field in a high-finesse micropillar cavity. Coherent exciton coupling is observed for two dots with energy differences of the order of the exciton-photon coupling. The coherent coupling mode is characterized by an anticrossing with a particularly large line splitting of 250 microeV. Because of the different dispersion relations with temperature, the simultaneous photonic coupling of quantum dot excitons can be easily distinguished from cases of sequential strong coupling of two quantum dots.

Journal Article↗
PubMed2006

Glycocalyx-mimetic dextran-modified poly(vinyl amine) surfactant coating reduces platelet adhesion on medical-grade polycarbonate surface.

A dextran-modified poly(vinyl amine) comb-like surfactant polymer, poly(N-vinyl dextran aldonamide-co-N-vinyl hexanamide), that can surface-adsorb on hydrophobic polymeric substrates, was designed to improve the interfacial blood-compatibility of polymeric biomaterials. Medical-grade polycarbonate was selected as a model substrate because of its extensive use in blood-contacting biomedical devices like hemodialyzers, blood pumps and oxygenators. The surfactant polymer was physisorbed from aqueous solution onto the polycarbonate substrate. The surfactant coating was stable under dynamic shear conditions in whole blood, as confirmed by fluorescence microscopy and total internal reflection fluorescence (TIRF) experiments with fluorescein-labeled surfactant polymer. The coated disks and uncoated control disks were exposed to platelet-rich plasma (PRP) and whole human blood in a rotating disk system (RDS) to study platelet-adhesion under dynamic shear stress environments. Adhered platelets were stained with fluorescein isothiocyante (FITC)-tagged anti-CD41a monoclonal antibody and imaged by epifluorescence microscopy. Complimentary images were obtained by phase-contrast microscopy. Platelet adhesion on the surfactant-coated disks was reduced by approximately 90%, compared with uncoated disks. The images also showed a concomitant reduction in platelet-derived microparticles on surfactant-coated disks, compared with uncoated disks. The results suggest potential application of carbohydrate-modified surfactant polymers as a glycocalyx-mimetic non-thrombogenic interfacial coating for blood-contacting biomaterials.

Adult↗
PubMed2006

Myeloradiculitis: a rare event in schistosoma infection.

Schistosomiasis a parasitic disease caused by trematodes is widely distributed in (sub-)tropical countries. Depending on the species the infection manifests clinically as gastrointestinal (preferentially Schistosoma mansoni and S. japonicum) or urinary (preferentially S. haematobium) disorders. Here we present an uncommon case of myeloradiculitis leading to bladder palsy and sensory loss at the lower limbs.

Adult↗
PubMed2006

Biosynthetic gene cluster for the polyenoyltetramic acid alpha-lipomycin.

The gram-positive bacterium Streptomyces aureofaciens Tü117 produces the acyclic polyene antibiotic alpha-lipomycin. The entire biosynthetic gene cluster (lip gene cluster) was cloned and characterized. DNA sequence analysis of a 74-kb region revealed the presence of 28 complete open reading frames (ORFs), 22 of them belonging to the biosynthetic gene cluster. Central to the cluster is a polyketide synthase locus that encodes an eight-module system comprised of four multifunctional proteins. In addition, one ORF shows homology to those for nonribosomal peptide synthetases, indicating that alpha-lipomycin belongs to the classification of hybrid peptide-polyketide natural products. Furthermore, the lip cluster includes genes responsible for the formation and attachment of d-digitoxose as well as ORFs that resemble those for putative regulatory and export functions. We generated biosynthetic mutants by insertional gene inactivation. By analysis of culture extracts of these mutants, we could prove that, indeed, the genes involved in the biosynthesis of lipomycin had been cloned, and additionally we gained insight into an unusual biosynthesis pathway.

Anti-Bacterial Agents↗
PubMed2005

Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults.

We evaluated the upper oesophageal sphincter (UOS) relationship with oesophageal body during primary peristalsis (PP) sequences in healthy human neonates during maturation and compared with that of healthy adult volunteers. Forty-nine studies were performed using a water perfusion manometry system and a specially designed oesophageal catheter with a UOS sleeve concurrent with submental electromyogram in 31 subjects in supine position (18 preterm neonates, 29.9 +/- 2.5 weeks gestation; four full-term neonates, 39.3 +/- 1.0 weeks gestation; and nine adults, 18-65 years). The preterm neonates were studied longitudinally at 33 and 36 weeks postmenstrual age (PMA) and full-term born at 40 weeks PMA. Data were compared between the groups to recognize the effects of gestation, postnatal age and ageing. We evaluated 403 consecutive spontaneous solitary swallows during maturation (preterm at time-1 vs time-2) and growth (preterm and full-term vs adults) and observed significant (P < 0.05) differences in the basal UOS resting pressure, UOS relaxation characteristics, proximal and distal oesophageal body amplitude, duration, propagation and peristaltic velocity. Characteristics of UOS and PP are well-developed by 33 weeks PMA and undergo further maturation during the postnatal period, and are significantly different from that of adult.

Adult↗
PubMed2004

Strong coupling in a single quantum dot-semiconductor microcavity system.

Cavity quantum electrodynamics, a central research field in optics and solid-state physics, addresses properties of atom-like emitters in cavities and can be divided into a weak and a strong coupling regime. For weak coupling, the spontaneous emission can be enhanced or reduced compared with its vacuum level by tuning discrete cavity modes in and out of resonance with the emitter. However, the most striking change of emission properties occurs when the conditions for strong coupling are fulfilled. In this case there is a change from the usual irreversible spontaneous emission to a reversible exchange of energy between the emitter and the cavity mode. This coherent coupling may provide a basis for future applications in quantum information processing or schemes for coherent control. Until now, strong coupling of individual two-level systems has been observed only for atoms in large cavities. Here we report the observation of strong coupling of a single two-level solid-state system with a photon, as realized by a single quantum dot in a semiconductor microcavity. The strong coupling is manifest in photoluminescence data that display anti-crossings between the quantum dot exciton and cavity-mode dispersion relations, characterized by a vacuum Rabi splitting of about 140 microeV.

Journal Article↗
PubMed2004

An optimised split-and-recombine micro-mixer with uniform chaotic mixing.

A second generation micro-mixer, being a further optimised version of a first prototype, relying on the consequent utilisation of the split-and-recombine principle is presented. We show that the mixing can be characterized by a positive finite-time Lyapunov exponent although being highly regular and uniform. Using computational fluid dynamics (CFD) we investigate the mixing performance for Reynolds numbers in the range of about 1 to about 100. In particular for low Reynolds numbers (Re < 15) the CFD results predict an almost ideal multi-lamination. Thus, the developed mixer is especially suited for efficient mixing of highly viscous fluids. Furthermore, the numerical results are experimentally validated by investigations of mixing of water-glycerol solutions. The experimental results are found to be in excellent agreement with the numerical data and prove the high mixing efficiency.

Journal Article↗
PubMed2003

Bioengineered human bone tissue using autogenous osteoblasts cultured on different biomatrices.

Surgical treatment of critical-size posttraumatic bone defects is still a challenging problem, even in modern bone and joint surgery. Progress in cellular and molecular biology during the last decade now permits novel approaches in bone engineering. Recent conceptual and technical advances have enabled the use of mitotically expanded, bone-derived cells as a therapeutic approach for tissue repair. Using three different tissue carrier systems, we successfully cultivated human osteoblasts in a newly developed perfusion chamber. We studied cell proliferation and the expression of osteocalcin, osteopontin, bone morphogenetic protein-2A, alkaline phosphatase, and vascular endothelial growth factor as parameters for osteoblast function and viability. Adherence of highly enriched human osteoblasts had already started after 1 h and resulted in completely overgrown human bone pieces after 10 days. Expression analysis of bone-specific alkaline phosphatase indicated differentiating osteoblasts, whereas the high mRNA expression of osteocalcin and osteopontin revealed terminally differentiated osteoblasts and the process of mineralization. Additionally, gene expression was significantly higher when demineralized bone was used as biomatrix, compared to autoclaved bone and hydroxyapatite ceramics. We conclude that with our newly developed perfusion culture system, vital autogenous bone implants of clinically applicable size can be generated within 17 days in order to manage critical-size bone defects.

Animals↗
PubMed2003

[Influence of processing and sterilization on the mechanical properties of pins made from bovine cortical bone].

In a biomechanical study pins made of xenogenous cortical bone were tested in vitro. Forty pins of 3 mm diameter and 60 mm length were made of eight different cattle tibiae and allocated to five different treatment groups. Freeze-dried pins served as control group. Pins of the second group were preserved in concentrated sodium chloride solution and defatted with acetone (Tuto-plast processing). Pins of groups three to five were treated with sodium chloride and acetone and afterwards sterilized by different means (ethylene oxide, autoclavation, or gamma radiation). All pins were subjected to a three-point-bending test and a shear test. We found that bending strength and shearing strength were most increased after sodium chloride and acetone treatment, whereas after sterilization with ethylene oxide or autoclaving, the stability of the pins was similar to the control group. The stability was considerably diminished after gamma radiation. Taking into account possible toxic side effects of ethylene oxide, we conclude that Tutoplast processing followed by autoclavation presents a reliable preparation method for the clinical use of implants made of bovine cortical bone.

Acetone↗
PubMed2002

Chances and shortcomins of adenovirus-mediated ATP7B gene transfer in Wilson disease: proof of principle demonstrated in a pilot study with LEC rats.

BACKGROUND & AIMS: Wilson disease (WD) is an autosomal recessively inherited copper storage disease due to mutations in the ATP7B gene. It results in impaired biliary copper excretion followed by liver injury leading to cirrhosis. In parallel, copper accumulates in other tissues e. g. basal ganglia of the brain inducing motoric disorders. Phenotypical cure of Wilson disease by liver transplantation raised the question whether gene therapy may represent a successful alternative treatment procedure. To examine the principle feasibility of this approach we investigated the effects of gene transfer using an adenoviral vector construct expressing the human ATP7B cDNA in an established rodent model for WD, the Long-Evans Cinnemon rat (LEC). METHODS: Transduction efficiency was assessed by RT-PCR, Western blot and immunofluorescence analysis. The therapeutic effect was estimated by analyzing holoceruloplasmin and its ferroxidase activity in serum, and the copper content of excrements. Changes in copper homeostasis were determined by positron emission tomography (PET). RESULTS: Successful, but temporary gene transfer was clearly detectable on RNA and protein levels. In parallel the temporary therapeutic effect was documented by restoration of serum holoceruloplasmin and of its ferroxidase activity. Additionally the Ad-ATP7B treated LEC rat revealed a higher (64)Cu content in stool. PET was able to visualize differences in (64)Cu distribution between wild type and LEC rats, indicating its principle usefulness as analytical tool. CONCLUSION: The data demonstrate proof of principle of successful gene therapy in an experimental model of WD. As a consequence of successful but only transient therapeutic effect of adenoviral gene transfer we can now focus more efficient and permanent gene transfer strategies.

Adenosine Triphosphatases↗
PubMed2001

Molecular basis of the neutrophil glycoprotein NB1 (CD177) involved in the pathogenesis of immune neutropenias and transfusion reactions.

The human granulocyte alloantigen NB1, recently clustered as CD177, is heterogenously expressed on neutrophils of 88-97% of healthy individuals. Since its molecular nature has remained unknown, we isolated NB1 glycoprotein from granulocyte lysate by immunoaffinity chromatography. MALDI-TOF mass spectrometry identified a 50,556 Da glycoprotein which was reduced to 43,069 Da after removal of N-linked carbohydrates. Following N-terminal amino acid sequencing and NB1-specific primer construction, rapid amplification of cDNA ends PCR yielded a 1,614-bp cDNA for NB1. COS-7 cells transfected with the cDNA expressed immunoreactive NB1 glycoprotein. A 1,311-bp sequence was identified to be the entire coding region. The 5' and 3' untranslated regions consist of 27 bp and 276 bp, respectively. The open reading frame codes for 437 amino acids of which the first 21 form the signal peptide. The remaining 416 residues form a N-terminal extracellular protein with two cysteine-rich domains, three N-linked glycosylation sites and short transmembrane and cytoplasmic segments including a glycosyl-phosphatidylinositol attachment (omega) site. Database searches revealed homology to Ly-6 (uPAR) domain, suggesting that NB1 belongs to urokinase plasminogen activator receptor/CD59/Ly-6 snake toxin superfamily.

Amino Acid Sequence↗
PubMed2001

[Strength testing of pins made of human femur cortical bone].

For biomechanical evaluation of cortical bone as a potential source for internal fixation devices, pins of 2 and 3 mm in diameter were made from fresh human femora and subjected to bending loads. Some of the pins were tested without further treatment; others were defatted and dried in acetone solution. Of the acetone-treated pins, some were autoclaved either at 121 degrees C for 20 min or at 134 degrees C for 8 min. Acetone treatment of the pins caused a 5.5% increase in bending strength (p < or = 0.05) and a 6.6% increase in the elastic modulus (p < or = 0.05). The mean bending strength of the acetone-treated pins was 257 +/- 52 N/mm2 and the mean elastic modulus was 18,346 +/- 1292 N/mm2. Autoclaving of the pins at the lower temperature for a longer time led to a decrease in the bending strength of up to 16% and at the higher temperature for a shorter time to a decrease of up to 41%. To compare the strengths of the cortical and synthetic pins, 2-mm Biofix pins were also tested. The Biofix pins showed a 25% higher bending strength than the acetone-treated pins but a 12.5% lower elastic modulus. It should be noted that in animal studies the synthetic Biofix pins showed a 20% loss of strength within 2 days after implantation in situ.

Bioprosthesis↗
PubMed2001

Sequential expression of annexin A5 in the vasculature and skeletal elements during mouse development.

Annexin A5 (annexin V, anchorin CII) represents the prototype member of the large annexin family, characterized by its ability to interact with phospholipids in a calcium-dependent manner and to form calcium-specific ion channels. Despite intense biochemical analysis, the in vivo expression and function of this annexin during mouse development, still remains unclear. Immunohistochemistry, in situ hybridization and reporter gene expression were used to define expression of annexin A5 during early mouse development. First, annexin A5 expression is associated with the developing vascular system. Later, expression is detected within the notochord and found in parallel to the differentiation of cartilage and bone. Therefore, expression of the Anxa5 gene may represent a novel marker characterizing cell lineages involved in the development of the vascular as well as the skeletal system.

Animals↗