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Biomedical subjects

C Hartmann

Publications and source records attributed to C Hartmann.

At least 19 recordsLinked to original sources
PubMed2007

Chromosomal imbalances and NF2 mutational analysis in a series of 10 spinal nerve sheath myxomas.

AIMS: To report the demographic, clinical and molecular profile of a series of intraspinal nerve sheath myxomas. Nerve sheath myxomas are diagnostically challenging, mainly cutaneous spindle cell neoplasms exhibiting Schwann cell differentiation. They are frequently mistaken for neurothekeomas and their genetic features are essentially unknown. METHODS AND RESULTS: Ten spinal nerve sheath myxomas with a preferential location in the lumbar spine (70%) were investigated. Presenting symptoms consisted of sciatic pain (100%), muscle weakness and paraesthesia (60% each). Intraoperatively, all tumours were attached to a spinal nerve. Chromosomal imbalances by comparative genomic hybridization were found in 8/10 cases, consisting of -22q (80%) and -19 (30%). Polymerase chain reaction analysis of the NF2 gene (exons 1-16) revealed two tumours with mutations in exon 8 and 14, respectively. CONCLUSIONS: Although these 10 nerve sheath myxomas exhibited Schwann cell differentiation and frequently showed loss of chromosome 22q typically encountered in peripheral nerve tumours, only two cases demonstrated mutations of the NF2 gene. This may indicate involvement of other tumour suppressor genes on 22q in nerve sheath myxomas and shows that they are more closely related at the molecular level to sporadic schwannomas, underscoring the presumption that they are true nerve sheath tumours.

Adult↗
PubMed2006

Role of canonical Wnt-signalling in joint formation.

The individual elements of the vertebrate skeleton are separated by three different types of joints, fibrous, cartilaginous and synovial joints. Synovial joint formation in the limbs is coupled to the formation of the prechondrogenic condensations, which precede the formation of the joint interzone. We are beginning to understand the signals involved in the formation of prechondrogenic condensations and the subsequent differentiation of cells within the condensations into chondrocytes. However, relatively little is known about the molecules and molecular pathways involved in induction of the early joint interzone and the subsequent formation of the synovial joints. Based on gain-of function studies Wnt-signalling, in particular the canonical pathway, has been implicated in the joint induction process. Here we provide genetic evidence from loss-of function analysis of embryos lacking either the central player of the canonical Wnt-pathway, beta-catenin, in the limb mesenchyme or the two ligands, Wnt9a and Wnt4, demonstrating that canonical Wnt-signalling plays an important role in suppressing the chondrogenic potential of cells in the joint thereby actively allowing joint formation. Furthermore our data show that the beta-catenin activity is not essential for the induction of molecular markers expressed in the joint interzone. Thus, suggesting that canonical Wnt-signalling is not required for the induction, but for the subsequent maintenance of the fate of the joint interzone cells.

Animals↗
PubMed2006

Experimental and numerical study of heterogeneous pressure-temperature-induced lethal and sublethal injury of Lactococcus lactis in a medium scale high-pressure autoclave.

The present contribution is dedicated to experimental and theoretical assessment of microbiological process heterogeneities of the high-pressure (HP) inactivation of Lactococcus lactis ssp. cremoris MG 1363. The inactivation kinetics are determined in dependence of pressure, process time, temperature and absence or presence of co-solutes in the buffer system namely 4 M sodium chloride and 1.5 M sucrose. The kinetic analysis is carried out in a 0.1-L autoclave in order to minimise thermal and convective effects. Upon these data, a deterministic inactivation model is formulated with the logistic equation. Its independent variables represent the counts of viable cells (viable but injured) and of the stress-resistant cells (viable and not injured). This model is then coupled to a thermo-fluiddynamical simulation method, high-pressure computer fluid dynamics technique (HP-CFD), which yields spatiotemporal temperature and flow fields occurring during the HP application inside any considered autoclave. Besides the thermo-fluiddynamic quantities, the coupled model predicts also the spatiotemporal distribution of both viable (VC) and stress-resistant cell counts (SRC). In order to assess the process non-uniformity of the microbial inactivation in a 3.3-L autoclave experimentally, microbial samples are placed at two distinct locations and are exposed to various process conditions. It can be shown with both, experimental and theoretical models that thermal heterogeneities induce process non-uniformities of more than one decimal power in the counts of the viable cells at the end of the treatment.

Biotechnology↗
PubMed2006

Combined high pressure and temperature induced lethal and sublethal injury of Lactococcus lactis--application of multivariate statistical analysis.

It was the aim of this work to determine the combined effects of pressure, temperature, and co-solutes on Lactococcus lactis, and to detect correlations between culture-dependent and culture-independent methods for assessment of cellular viability and sublethal injury. Therefore, the pressure induced inactivation of L. lactis MG 1363 was investigated in buffer and in buffer with 1.5 M sucrose or 4 M NaCl at a pressure range of 0.1 to 500 MPa and a temperature range of 5 to 50 degrees C. The inactivation was characterised by viable cell counts, stress resistant cell counts, membrane integrity, metabolic activity, and the activity of the multi-drug-resistance transport enzyme LmrP. L. lactis was most resistant to pressure application at 20-30 degrees C. Sucrose protected towards inactivation at any temperature, NaCl provided protection at high temperatures only. By using Principal Component Analysis, correlations were detected between viable cell counts and metabolic activity as well as stress resistant cell counts and LmrP activity. In conclusion, the pressure-inactivation of L. lactis is strongly temperature dependent, baroprotection by sucrose occurs at any temperature but the baroprotective effects of NaCl is temperature dependent. Further on, a combination of two experimental methods fully describe lethal and sublethal injury of pressure treated cells. These simplification of data acquisition and model development facilitates the establishment of pressure processes in food technology.

Bacterial Proteins↗
PubMed2006

[Reconstruction of skin defects in the eyelid and periorbital region using four triangular advancement flaps. An alternative to free skin grafts].

PURPOSE: This report presents a procedure as an alternative to free skin grafts for reconstruction of rhomboid skin defects in the lid region. METHOD: Ten consecutively treated patients were included who had skin defects after resection of eyelid tumors such as basaliomas. The skin defects were rhomboid and had the same horizontal and vertical diameter (medium 1.5 cm) and were therefore too large for a horizontal advancement flap. The defects were closed by preparation of four triangular skin flaps that were sutured crosswise into the defect. RESULTS: The procedure was adequate for reconstruction of the defect in all ten cases. There were no lid malpositions and the cosmetic results were favorable in all cases. The medium operation time was significantly shorter in comparison to free skin grafts. CONCLUSIONS: Application of free skin grafts is a standard procedure for reconstruction of anterior lamellar lid defects. Triangular transposition flaps can be a timesaving alternative with good cosmetic results.

Aged↗
PubMed2005

MLPA analysis for the detection of deletions, duplications and complex rearrangements in the dystrophin gene: potential and pitfalls.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-chromosomal recessive disorders caused by mutations in the dystrophin gene. Using the novel multiplex ligation-dependent probe amplification (MLPA) method we performed retrospective and prospective analyses in a total of 193 individuals. Deletions or duplications were identified in 14 out of 90 families previously tested negative by multiplex PCR or FISH analysis. Partially incorrect results were subsequently identified in two families: the loss of exon 38 signal in one case was due to a p.Q1802X nonsense mutation, whilst in another patient an apparent deletion of exon 37 (coinciding with a duplication of exons 46-53) was caused by a p.R1735C polymorphism. In one case we found a complex rearrangement involving a duplication of two regions: dupEX45-48 and dupEX54-55. We conclude that MLPA is a highly sensitive and rapid alternative to multiplex PCR. It can be used on blood samples, chorionic villi and paraffin-embedded tissue. The ease of detection of duplications and the application for female carrier analysis are clearly the main advantages of the method. However, apparent single exon deletions detected by MLPA should be checked by an independent method. Complex rearrangements such as double mutations on the same allele are rare.

DNA Primers↗
PubMed2005

A fuzzy logic-based model for the multistage high-pressure inactivation of Lactococcus lactis ssp. cremoris MG 1363.

The high-pressure inactivation (200 to 600 MPa) of Lactococcus lactis ssp. cremoris MG 1363 suspended in milk buffer was investigated with both experimental and theoretical methods. The inactivation kinetics were characterised by the determination of the viable cell counts, cell counts of undamaged cells, LmrP activity, membrane integrity, and metabolic activity. Pressures between 200 and 600 MPa were applied, and pressure holding times were varied between 0 and 120 min. Experiments were carried out in milk buffer at pH values ranging between 4.0 and 6.5, and the effect of the addition of molar concentrations of NaCl and sucrose was furthermore determined. The inactivation curves of L. lactis, as characterised by viable cell counts, exhibited typical sigmoid asymmetric shapes. Generally, inactivation of the membrane transport system LmrP was the most sensitive indicator of pressure-induced sublethal injury. Furthermore, the metabolic activity was inactivated concomitant with or prior to the loss of viability. Membrane integrity was lost concomitant with or later than cell death. For example, treatments at 200 MPa for 60 min in milk buffer did not inactivate L. lactis, but fully inactivated LmrP activity and reduced the metabolic activity by 50%. The membrane integrity was unaffected. Thus, the assay systems chosen are suitable to dissect the multistep high-pressure inactivation of L. lactis ssp. cremoris MG 1363. A fuzzy logic model accounting for the specific knowledge on the multistep pressure inactivation and allowing the prediction of the quantities of sublethally damaged cells was formulated. Furthermore, the fuzzy model could be used to accurately predict pressure inactivation of L. lactis using conditions not taken into account in model generation. It consists of 160 rules accounting for several dependent and independent variables. The rules were generated automatically with fuzzy clustering methods and rule-oriented statistical analysis. The set is open for the integration of further knowledge-based rules. A very good overall agreement between measured and predicted values was obtained. Single, deviating results have been identified and can be explained to be measurement errors or model intrinsic deficiencies.

Animals↗
PubMed2005

[Non-contact donor cornea trephination with a flying spot excimer laser system].

BACKGROUND: One of the most common complications after mechanical penetrating keratoplasty is the occurrence of irregular astigmatism. We developed a method to prepare donor grafts for transplantation applying excimer laser techniques. The quality of the cut edges and exposure time were evaluated. MATERIALS AND METHODS: The beam of an experimental excimer laser (OPTex, Lambda Physik) was homogenized and guided by an optical system including lenses and scanner mirrors. A special software was used to conduct the laser beam in a circular mode over the surface of the cornea. Corneas from porcine eyes were stabilized in an artificial anterior chamber. Twenty in vitro explants were trephinated applying our method and subsequently investigated by electron microscopy and histology. RESULTS: All experiments provided regular and smooth cut edges. The average exposure time until perforation was 10.5 min (SD 2.7 min), the diameter of the grafts was 8.0 mm. CONCLUSION: The experiments showed the possibility of non-contact trephination and generation of smooth cut edges with a rotating focussed excimer laser beam in a porcine cornea model. A major advantage of the system is the possibility of customized "tailored" grafts.

Angioplasty, Balloon, Laser-Assisted↗
PubMed2005

Helicobacter pylori infection in anterior uveitis.

BACKGROUND: Despite intensive research, the etiology of acute anterior uveitis (AAU) remains poorly defined. Infection with gram-negative bacteria such as Yersinia, Salmonella, Shigella, and Chlamydia have already been suggested as a possible trigger event for AAU. Helicobacter pylori is also a gram-negative bacterium, shares the lipopolysaccharides, but did not attract the attention of many ophthalmologists until recently. Having in mind the relatively high incidence of H. pylori infection in the population, we propose that H. pylori may also be a trigger factor for AAU. PATIENTS AND METHODS: The presence of anti-H. pylori antibodies in matching serum and aqueous humor samples of 15 idiopathic AAU patients was determined using a commercial Western blot assay. Control serum and aqueous humor were obtained from five patients undergoing cataract surgery. RESULTS: Six out of 15 AAU patients (40%) were serum-positive for H. pylori, and half of these (n = 3) also had anti-H. pylori antibodies in the aqueous humor. All five aqueous humor and sera controls tested negative for H. pylori infection. CONCLUSION: These are the first results demonstrating anti-H. pylori antibodies in the aqueous humor of AAU patients. Further studies are needed to demonstrate whether this antibody is indeed locally produced. Our data may provide first evidence for a causative link between H. pylori infection and AAU.

Adult↗
PubMed2005

Differential inactivation of glucose- and glutamate dependent acid resistance of Escherichia coli TMW 2.497 by high-pressure treatments.

The inactivation by 200-400 MPa and post-pressure survival at acid conditions of E. coli TMW 2.497 was characterized by the measurement of intracellular pH (pHin), viable cell counts, glutamate (Glu) and arginine (Arg) consumption, and the influence of mild adaptation to mild acid stress prior to pressure treatment. Glutamate and arginine did not affect viable cell counts or the pHin during pressure application but improved the ability to maintain a high pHin after pressure treatment. In pH 4.0 buffer without arg and glu, a 3 log reduction of cell counts occurred after 24 h of incubation, whereas little or no loss of viability was observed after 24 h incubation in the presence of glu and arg. During post-pressure incubation at pH 4.0, 10 mM glutamate were metabolized but only 2 mM arginine were used, indicating that glutamate rather than arginine was responsible for the protective effect on pHin and survival. In conclusion, the pressure induced, irreversible loss of the transmembrane deltapH correlates to cell death and glu stabilizes the pHin of E. coli during post-pressure incubation.

Acids↗
PubMed2005

Oligodendrogliomas: impact of molecular genetics on treatment.

The interest in oligodendrogliomas has increased since it became evident that a subset of these tumors respond to chemotherapy or radiation. This interest was augmented when the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 was identified as a powerful prediction factor for response. Lack of stringent morphological criteria allow high-interobserver variation with regard to classification and grading of oligodendroglial tumors. The prospect of beneficial chemotherapy prompted neuropathologists to diagnose more 'oligodendroglioma' than before. Therefore, there is great demand for unambiguous classification of oligodendroglial tumors. Supplementary analysis of the integrity of chromosomal arms 1p and 19q may greatly assist diagnostic characterization of tumors with oligodendroglial phenotype. The underlying mechanisms for these deletions are not known. Tumor suppressor genes on 1p and 19q relevant for oligodendroglioma have not yet been identified. Knowledge of these genes and the mechanisms of their inactivation might help to understand why oligodendroglial tumors do respond better to chemotherapy and radiotherapy than astrocytomas. This review compiles clinical, pathological and molecular genetic findings on oligodendrogliomas and oligoastrocytomas of WHO Grades II and III to present a brief overview on recent developments.

Animals↗
PubMed2005

Disinfection by-products and microbial contamination in the treatment of pool water with granular activated carbon.

For swimming pools, it is generally agreed that free chlorine levels have to be maintained to guarantee adequate disinfection. Recommended free chlorine levels can vary between 0.3 and 0.6 mg/L in Germany and up to 3 mg/L in other countries. Bathers introduce considerable amounts of organic matter, mainly in the form of such as urine and sweat, into the pool water. As a consequence, disinfection byproducts (DBPs) are formed. Regulations in Germany recommend levels of combined chlorine of less than 0.2 mg/L and levels of trihalomethanes (THMs) of less than 20 microg/L. Haloacetic acids (HAAs), haloacetonitriles (HANs), chloropicrin and chloral hydrate are also detected in considerable amounts. However, these compounds are not regulated yet. Swimming pool staff and swimmers, especially athletes, are primarily exposed to these byproducts by inhalation and/or dermal uptake. In Germany, new regulations for swimming pool water treatment generally require the use of activated carbon. In this project, three different types of granular activated carbon (GAC) (one standard GAC, two catalytic GACs) are compared for their long time behaviour in pool water treatment. In a pilot plant operated with real swimming pool water, production and removal of disinfection byproducts (THMs, HAAs, AOXs), of biodegradable substances (AOC), of bacteria (Pseudomonas aeruginosa, Legionella, coliforms, HPC) as well as the removal of chlorine and chloramines are monitored as function of GAC bed depth. Combined chlorine penetrates deeper in the filter bed than free chlorine does. However, both, free and combined chlorine removal efficiencies decrease over the time of filter operation. The decreases of removal efficiencies are also observed for parameters such as dissolved organic carbon, spectral absorption coefficient, adsorbable organic carbon and most of the disinfection byproducts. However, THMs, especially chloroform are produced in the filter bed. The GAC beds were contaminated microbially, especially with P. aeruginosa. The contamination was not removable by backwashing with chlorine concentrations up to 2 mg/l free chlorine.

Charcoal↗
PubMed2004

Evaluation of a human capsular bag model for secondary cataract determination after intraocular lens implantation.

PURPOSE: To investigate the effect of different intraocular lenses (IOLs) on lens epithelial cells (LECs) and on human capsular bags in vitro and to evaluate the transferability of this model to clinical situations. METHODS: Sham cataract surgery, including IOL-into-the-bag implantation, was performed on 38 donor eyes after removal of the cornea. The capsular bag including the IOL was removed, pinned on a culture dish, covered with medium, and incubated. Two different IOLs were compared per pair of donor eyes. In each pair of donor eyes, the two different IOLs to be compared were implanted individually into capsular bags. The time required for complete coverage of the posterior capsule by a confluent monolayer of LECs was documented. The following IOLs were compared: three-piece acrylic IOLs of different sizes and single-piece polymethylmethacrylate (PMMA) versus acrylic IOLs. RESULTS: A complete monolayer of LECs on the posterior capsule was observed to form at times varying from 8 days (PMMA IOLs) to more than 60 days (three-piece hydrophobic acrylic IOLs). A significant difference between PMMA IOLs and hydrophobic acrylic IOLs was found. CONCLUSIONS: The human capsular bag model employed allows short-term evaluation of secondary cataract formation for different IOLs. This model's correlation with clinical results is good.

Acrylic Resins↗
PubMed2004

[Effect of suramin on proliferation and migration of lens epithelial cells in vitro].

BACKGROUND: New approaches for the treatment of secondary cataract focus on a pharmacological therapy to prevent posterior capsule opacification. In this study we investigated the effect of the naphthylurea suramin in vitro in a cell culture model. MATERIAL AND METHODS: Cell proliferation was measured using a proliferation assay and cell migration with a migration assay. Analyses of suramin toxicity were carried out using trypan blue staining. RESULTS: A significant dose-dependent effect of suramin on the inhibition of LEC proliferation and migration was found even after short (1 or 2 h) incubation times ( p<0.01). Cell lysis reflecting a cytotoxic effect of suramin was not found even with high concentrations. However, preincubation of lens capsules with suramin did not prevent LECs from migrating compared to control cultures. CONCLUSION: These results demonstrate the efficiency of suramin in vitro to inhibit migration of HLEC which can be explained by blocking growth factor-mediated effects on the cells. However, further investigations on the pharmacokinetic properties of suramin and possible side-effects on other intraocular tissues must follow.

Cell Division↗
PubMed2003

[Ocular toxocariasis. Diagnostic and therapeutic options].

BACKGROUND: The diagnosis of ocular toxocariasis can be difficult and the aim of this study was to evaluate the benefit of ELISA testing of vitreous body fluid. PATIENTS AND METHODS: We present five consecutively treated patients with ocular symptoms of toxocariasis, three of these patients presenting with epiretinal membranes and subretinal granulomas were vitrectomized. Vitreous and body fluid and serum were tested for toxocara antibodies by ELISA. Moreover vitreous body fluid of 10 patients with epiretinal membranes of other origins were examined by the same ELISA. RESULTS: In all three operated patients toxocara antibodies were detected in the vitreous fluid but ELISA testing of serum samples was negative in two of the three patients. Visual acuity increased or remained stable in the operated patients. The ELISA test was negative in all vitreous fluid samples of the control group. CONCLUSIONS: ELISA testing of vitreous body fluid can prove the presence of toxocara infection when no systemic signs of infection are present and no antibodies are detectable in the serum. Well-timed vitrectomy is a suitable therapy for vitreo-retinal complications in ocular toxocariasis to improve prognosis and to confirm the diagnosis.

Adolescent↗
PubMed2003

[Transcorneal-paracorneal penetration route for topical application of drugs to the eyt. Mycophenolate mofetil as a model substance].

PURPOSE: Topically applied drugs can penetrate transcorneally or paracorneally (transsclerally). There are only few studies to demonstrate the relationship of both penetration routes. The immuno-modulator mycophenolate mofetil (MMF), ester and pro-drug of mycophenolic acid (MPA), is a promising substance for such studies. MATERIAL AND METHODS: Rabbit eyes were treated with different preparations of MMF as a cyclodextrin complex (MM-CD) and as a suspension (MMF-SP) and MPA as a cyclodextrin complex (MPA-CD). The concentrations of both compounds were measured in the cornea, conjunctiva, aqueous humor, vitreous body and iris-ciliary body. RESULTS: Only MPA is detectable in the cornea after application of MMF-CD and MMF-SP. In the aqueous humor high concentrations of MPA are detectable after 60 min. In the iris-ciliary body both MMF and MPA can be found. CONCLUSION: The intraocularly detected mycophenolate mofetil represents the paracorneally penetrated fraction. After topical application of mycophenolate mofetil in suitable preparations high concentrations of the active substance can be achieved intraocularly. These favourable pharmacokinetic characteristics are promising for new therapeutic strategies in immune-mediated diseases of the anterior part of the eye.

Administration, Topical↗
PubMed2003

Development of protein microarray technology to monitor biomarkers of rheumatoid arthritis disease.

Most biological processes are mediated by complex networks of molecular interactions involving proteins. The analysis of protein expression in biological samples is especially important in the identification and monitoring of biomarkers for disease progression and therapeutic endpoints. In this paper, the development of a protein microarray format for multiplexed quantitative analysis of several potential markers for rheumatoid arthritis (RA) is described. Development of a high-performance protein microarray system depends on several key parameters such as surface chemistry, capture agents, immobilization technology, and methods used for signal detection and quantification. Several technical possibilities were investigated and compared: poly-L-lysine versus self-assembled monolayer of octadecyl phosphoric acid ester for surface chemistries; noncontact piezoelectric versus contact printing technology for antibody deposition; CCD camera capture versus fluorescent scanning for image detection; and the concentration of coating antibody. On the basis of reproducibility, signal-to-noise ratio, and sensitivity we have selected self-assembled monolayer, noncontact piezoelectric printer, and high-read-out fluorescence scanning for our microarray format. This format was used to perform multiplexed quantitative analysis of several potential markers of disease progression of rheumatoid arthritis: IL-1beta, IL-6, IL-8, MCP-1, and SAA. Some assays, such as MCP-1, provided a working range that covered physiologically relevant concentrations. Other assays, such as IL-6 and SAA, lacked sensitivity or were too sensitive for measuring biological concentrations, respectively. The results described demonstrate the applicability of protein microarrays to monitor RA markers; however, sandwich assay methodologies need to be further optimized to measure the appropriate biological ranges of these markers on one chip.

Arthritis, Rheumatoid↗