Biomedical subjects

J Reichert

Publications and source records attributed to J Reichert.

At least 19 recordsLinked to original sources

PubMed2007

European dissemination of a web- and case-based learning system for occupational medicine: NetWoRM Europe.

OBJECTIVE: Occupation has a large impact on health in Europe. In order to prevent and recognize occupational diseases, medical students and physicians should know about the potentially causal relationship between profession and diseases as well as the basic legal aspects of occupational medicine (OM). However, the opportunity of bedside teaching, the students' most favoured way of teaching, is limited. METHODS: One possibility to complete and improve traditional training in OM is computer-oriented case-based learning. Using the authoring system "CASUS" (INSTRUCT AG) cases can be created and handled without knowledge in computer sciences. RESULTS: So far, 19 cases have been created and evaluated by students of German universities. Due to the great efforts arising from the creation of such multimedia cases it is desirable and cost-effective to use the existing cases at several medical universities. Therefore, the Net-based Training in Work-Related Medicine (NetWoRM) project shares cases on an international base. In February and April 2005, 13 case-authors from 12 centres were trained in the basics of case creation during a 3 week programme in Munich. The overall evaluation of the participants indicated that this way of teaching case creation is very efficient. Up to now, nine cases were translated into English and five into Spanish. First implementation of the cases in Spain and Finland showed a good acceptance by the students but more evaluation has still to be done. CONCLUSION: Based on these results we conclude that exchange of case-based e-learning in OM is feasible and rewarding on an international base.

Case-Control Studies↗

PubMed2006

Needlestick injuries during medical training.

Medical students are at risk of acquiring infections caused by needlestick injuries, although it is unknown when needlestick injuries are most likely to occur during medical training. The aim of this study was to define high-risk periods over the course of medical training. A cross-sectional study was conducted among medical students in the first, third, fourth and fifth years of training at two medical schools in Munich. Overall, 1317 (85%) students returned a questionnaire on demographic data, vaccination status against hepatitis B, lifetime prevalence of needlestick injuries, level of knowledge about measures after such accidents, and transmission risks. Lifetime prevalence of needlestick injuries was 23%, ranging from 12% in first year students to 41% in fourth year students. These accidents happened most commonly during medical internships, especially during blood-taking practices; an activity that usually starts during the third year of training. The frequency of respondents not vaccinated against hepatitis B also varied between first (21%) and fourth (6.6%) year students. Needlestick injuries occur frequently and early on in medical training. In order to decrease the risk of preventable infections, complete coverage of vaccination against hepatitis B should be achieved early in medical training.

Adult↗

PubMed2006

[Acute effects on the health of children after accidental exposure to epichlorohydrine].

PURPOSE: In September 2002, two freight trains collided at Bad Muender, Germany. The inhabitants were potentially exposed to combustion products and to the human carcinogen epichlorohydrine (ECH). We aimed to describe the geographical distribution of and potential risk factors for acute symptoms among children residing in Bad Muender. METHODS: The parents of a random sample of children were invited to answer a mail-in questionnaire (response rate 63%). The main outcome measures were self-reported acute symptoms potentially associated with combustion products (e. g., irritation of the eyes, nose, or throat) and stress-related unspecific symptoms (e. g., gastrointestinal complaints, sleep problems, headaches). The main location during the first 26 hours after the train accident served as exposure proxy measure. In addition, potential predictors for the symptoms under study were assessed. RESULTS: The prevalence of symptoms associated with combustion products was 5.9%. Unspecific symptoms were reported for 6.3% of the children. Main location and prevalence of symptoms were not significantly associated. Physician-diagnosed asthma and nasal allergies were the main predictors of symptoms. CONCLUSION: The prevalence of acute symptoms was relatively high in a random sample of children living close to the incident. However, associations between exposure to the accident and symptoms could not be established conclusively.

Accidents↗

PubMed2004

Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects.

BACKGROUND: Within the context of the hygiene hypothesis, we aimed to study the potential association between farming-related risk factors and Toxoplasma gondii (T. gondii) as well as Helicobacter pylori (H. pylori) seropositivity. METHODS: The study included questionnaire data and serum samples of 321 young adults living in a rural environment. Serum samples were analysed for specific IgE to a common panel of aeroallergens (SX1) as well as IgG against T. gondii and H. pylori. RESULTS: Regular contact with animal stables before the age of 3 years (odds ratio (OR) (95% confidence interval): 2.0 [1.0; 4.0]) and unpasteurized milk consumption at age 6 years (1.8 [1.0; 3.3]) were the strongest risk factors for T. gondii infection. None of the farming-related factors were significantly associated with H. pylori infection. Current consumption of raw farm milk was not significantly associated with H. pylori infection (2.1 [0.8; 5.3]). Regular contact with animal houses before the age of 7 years was the strongest predictor for atopy (0.49 [0.26-0.96]). The reduction in risk could not be further decreased by any other factor under consideration. After adjustment for animal house contact, the OR for atopy was decreased by raw milk consumption and H. pylori infection in an additive manner. CONCLUSION: Exposure to farming environments in childhood might predict T. gondii seropositivity in rural subjects. Nevertheless, the strongest predictor for atopy in rural subjects seems to be regular contact with farm animals. Whether T. gondii infection is an intermediate factor in the association between farm contact and atopy needs to be confirmed in larger studies.

Adult↗

PubMed2003

Toxoplasma gondii infection, atopy and autoimmune disease.

While for many allergens a dose-response relationship has clearly been established the association between early childhood exposure to cat allergens and risk of sensitisation is still controversial and even inverse relations have been described. At the same time, a negative association between Toxoplasma gondii (T. gondii) infection and atopic diseases has been found in epidemiologic studies. As cats are the major source of T. gondii oocysts, we hypothesize that cat allergen exposure might be a confounder in the association between T. gondii infection and allergic diseases. Furthermore, it is well known that atopic diseases are T helper cell 2 (Th2) driven while autoimmune diseases are dominated by a Th1 response. A counterbalance between Th1 and Th2 cells has been postulated. However, it has been shown recently that subjects with autoimmune disease are more likely to suffer from atopic diseases. Therefore, similar cytokine profiles might underlie these disorders. If this holds true it can be hypothesised that T. gondii infection is associated with a lower prevalence of autoimmune disease.

Allergens↗

PubMed2003

Sodium channels SCN1A, SCN2A and SCN3A in familial autism.

Autism is a psychiatric disorder with estimated heritability of 90%. One-third of autistic individuals experience seizures. A susceptibility locus for autism was mapped near a cluster of voltage-gated sodium channel genes on chromosome 2. Mutations in two of these genes, SCN1A and SCN2A, result in the seizure disorder GEFS+. To evaluate these sodium channel genes as candidates for the autism susceptibility locus, we screened for variation in coding exons and splice sites in 117 multiplex autism families. A total of 27 kb of coding sequence and 3 kb of intron sequence were screened. Only six families carried variants with potential effects on sodium channel function. Five coding variants and one lariat branchpoint mutation were each observed in a single family, but were not present in controls. The variant R1902C in SCN2A is located in the calmodulin binding site and was found to reduce binding affinity for calcium-bound calmodulin. R542Q in SCN1A was observed in one autism family and had previously been identified in a patient with juvenile myoclonic epilepsy. The effect of the lariat branchpoint mutation was tested in cultured lymphoblasts. Additional population studies and functional tests will be required to evaluate pathogenicity of the coding and lariat site variants. SNP density was 1/kb in the genomic sequence screened. We report 38 sodium channel SNPs that will be useful in future association and linkage studies.

Autistic Disorder↗

PubMed2002

Driving current through single organic molecules.

We investigate electronic transport through two types of conjugated molecules. Mechanically controlled break junctions are used to couple thiol end groups of single molecules to two gold electrodes. Current-voltage characteristics ( IVs) of the metal-molecule-metal system are observed. These IVs reproduce the spatial symmetry of the molecules with respect to the direction of current flow. We hereby unambiguously detect an intrinsic property of the molecule and are able to distinguish the influence of both the molecule and the contact to the metal electrodes on the transport properties of the compound system.

Journal Article↗

PubMed2002

Association between a GABRB3 polymorphism and autism.

Autistic disorder (OMIM 209850) is a disease with a significant genetic component of a complex nature.(1) Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (15q11-13) have been described in several individuals with autism.(1) For this reason, markers across this region have been screened for evidence of linkage and association, and a marker (155CA-2) in the gamma-aminobutyric acid type-A receptor beta3 subunit gene (GABRB3) has been associated in one study(2) but not others.(3-5) We completed an association analysis with 155CA-2 using the transmission disequilibrium test (TDT) in a set of 80 autism families (59 multiplex and 21 trios). We also used four additional markers (69CA, 155CA-1, 85CA, and A55CA-1) localized within 150 kb of 155CA-2. The use of multi-allelic TDT (MTDT) (P < 0.002), as well as the TDT (P < 0.004), demonstrated an association between autistic disorder and 155CA-2 in these families. Meiotic segregation distortion could be excluded as a possible cause for these results since no disequilibrium was observed in unaffected siblings. These findings support a role for genetic variants within the GABA receptor gene complex in 15q11-13 in autistic disorder.

Autistic Disorder↗

PubMed2001

Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity.

Although there is considerable evidence for a strong genetic component to idiopathic autism, several genomewide screens for susceptibility genes have been performed with limited concordance of linked loci, reflecting either numerous genes of weak effect and/or sample heterogeneity. Because decreasing sample heterogeneity would increase the power to identify genes, the effect on evidence for linkage of restricting a sample of autism-affected relative pairs to those with delayed onset (at age >36 mo) of phrase speech (PSD, for phrase speech delay) was studied. In the second stage of a two-stage genome screen for susceptibility loci involving 95 families with two or more individuals with autism or related disorders, a maximal multipoint heterogeneity LOD score (HLOD) of 1.96 and a maximal multipoint nonparametric linkage (NPL) score of 2.39 was seen on chromosome 2q. Restricting the analysis to the subset of families (n=49) with two or more individuals having a narrow diagnosis of autism and PSD generated a maximal multipoint HLOD score of 2.99 and an NPL score of 3.32. The increased scores in the restricted sample, together with evidence for heterogeneity in the entire sample, indicate that the restricted sample comprises a population that is more genetically homogeneous, which could therefore increase the likelihood of positional cloning of susceptibility loci.

Autistic Disorder↗

PubMed2000

Chip-based optical detection of DNA hybridization by means of nanobead labeling.

A new scheme for the detection of molecular interactions based on optical readout of nanoparticle labels has been developed. Capture DNA probes were arrayed on a glass chip and incubated with nanoparticle-labeled target DNA probes, containing a complementary sequence. Binding events were monitored by optical means, using reflected and transmitted light for the detection of surface-bound nanoparticles. Control experiments exclude significant influence of nonspecific binding on the observed contrast. Scanning force microscopy revealed the distribution of nanoparticles on the chip surface.

Base Sequence↗

PubMed2000

Measurement of the hydrogen 1S- 2S transition frequency by phase coherent comparison with a microwave cesium fountain clock

We report on an absolute frequency measurement of the hydrogen 1S-2S two-photon transition in a cold atomic beam with an accuracy of 1.8 parts in 10(14). Our experimental result of 2 466 061 413 187 103(46) Hz has been obtained by phase coherent comparison of the hydrogen transition frequency with an atomic cesium fountain clock. Both frequencies are linked with a comb of laser frequencies emitted by a mode locked laser.

Journal Article↗

PubMed2000

Dynamic interaction of plastocyanin with the cytochrome bf complex.

The interaction between plastocyanin and the intact cytochrome bf complex, both from spinach, has been studied by stopped-flow kinetics with mutant plastocyanin to elucidate the site of electron transfer and the docking regions of the molecule. Mutation of Tyr-83 to Arg or Leu provides no evidence for a second electron transfer path via Tyr-83 of plastocyanin, which has been proposed to be the site of electron transfer from cytochrome f. The data found with mutations of acidic residues indicate that both conserved negative patches are essential for the binding of plastocyanin to the intact cytochrome bf complex. Replacing Ala-90 and Gly-10 at the flat hydrophobic surface of plastocyanin by larger residues slowed down and accelerated, respectively, the rate of electron transfer as compared with wild-type plastocyanin. These opposing effects reveal that the hydrophobic region around the electron transfer site at His-87 is divided up into two regions, of which only that with Ala-90 contributes to the attachment to the cytochrome bf complex. These binding sites of plastocyanin are substantially different from those interacting with photosystem I. It appears that each of the two binding regions of plastocyanin is split into halves, which are used in different combinations in the molecular recognition at the two membrane complexes.

Amino Acid Substitution↗

PubMed2000

Phase coherent vacuum-ultraviolet to radio frequency comparison with a mode-locked laser

We demonstrate a versatile new technique that provides a phase coherent link between optical frequencies and the radio frequency domain. The regularly spaced comb of modes of a mode-locked femtosecond laser is used as a precise ruler to measure a large frequency gap between two different multiples (harmonics or subharmonics) of a laser frequency. In this way, we have determined a new value of the hydrogen 1S-2S two-photon resonance, f(1S-2S) = 2 466 061 413 187.29(37) kHz, representing now the most accurate measurement of an optical frequency.

Journal Article↗

PubMed2000

The IMB Jena Image Library of biological macromolecules.

The IMB Jena Image Library of Biological Macro-molecules (http://www. imb-jena.de/IMAGE.html ) is aimed at a better dissemination of information on three-dimensional biopolymer structures with an emphasis on visualization and analysis. It provides access to all structure entries deposited at the Protein Data Bank (PDB) and Nucleic Acid Database (NDB). By combining automatic and manual processing it is possible to keep pace with the rapidly growing number of known biopolymer structures and to provide, for selected entries, information not available from automatic procedures. Each entry page contains basic information on the structure, various visualization and analysis tools as well as links to other databases. The visualization techniques adopted include static mono/stereo raster or vector graphics representations, virtual reality modeling (VRML), RasMol/Chime scripts and Java applets. A helix and bending analysis tool provides consistent information on about 750 DNA and RNA duplex structures. Access to metal-containing PDB entries is possible via the Periodic Table of Elements. Finally, general information on amino acids, cis -peptide bonds, structural elements in proteins, base pairs, nucleic acid model conformations and experimental methods for biopolymer structure determination is provided.

Biopolymers↗

PubMed1998

Functional analysis of the human cytochrome P4501A1 (CYP1A1) gene enhancer.

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) induces gene transcription, a process that requires binding of the activated aryl hydrocarbon receptor (AhR) to dioxin-responsive elements (DREs) within the enhancer region of responsive genes. Most of what is known about the molecular mechanism of AhR-dependent gene activation results from studies on the murine prototype TCDD-responsive gene cytochrome P4501A1 (CYP1A1). Much less is known, however, about the regulation of human TCDD-responsive genes. We have therefore conducted a detailed analysis of the enhancer region of the human CYP1A1 gene. From the ten DRE core motifs investigated within a stretch of 1400 bp in two human tumor cell lines using a ligation-mediated PCR technique, five motifs displayed a TCDD-inducible in vivo footprint. Four of these sites were functional enhancer sequences as demonstrated by a transient expression assay. Based on these data, a distinct functional consensus sequence for DRE motifs within the human CYP1A1 gene is suggested. After introduction of the four functional sites into various mouse hepatoma cell lines, only three exhibited a functional response, suggesting some species differences in CYP1A1 gene regulation. In addition to the footprints at DRE sites, we also detected protein-DNA interactions at three G-rich domains located within the enhancer region of the human CYP1A1 gene. Our data show that, besides some similarities in the regulation of the human and mouse CYP1A1 genes, there also exist some distinct differences, including number, location, and functional consensus sequences of DRE motifs, as well as quantity and location of footprinted G-rich domains.

Animals↗

PubMed1998

Expression of hypoxia-inducible genes in tumor cells.

Tumor tissue oxygenation impacts on proliferation of cancer cells and their sensitivity towards radio- and chemotherapy. Under low oxygen, mammalian cells show an adaptive response that leads to the induction of a number of genes with well-defined roles in oxygen supply and energy maintenance, e.g. genes encoding enzymes of the glycolytic pathway. The hypoxia-inducible factor 1 (HIF-1), a transcription factor consisting of the two proteins HIF-1alpha and HIF-1beta, plays a major role in the pleiotropic response observed under low oxygen. We have determined, by Northern analysis, the mRNA levels of HIF-1alpha and of two glycolytic enzymes known to be transcriptionally activated by HIF-1, namely phosphoglycerate kinase 1 (PGK 1) and pyruvate kinase M2 (PKM2), in different hepatoma cell lines and in mouse and human tissues. Hypoxic treatment of various mouse and human hepatoma cell lines led to the expected increase in the amount of PGK1 and PKM2 mRNA, while HIF-1alpha mRNA levels were not significantly elevated. Analysis of mouse liver tumors demonstrated no tumor-specific increases in HIF-1alpha or PGK1 mRNA levels. In five of eight human colorectal cancers investigated, PGK1 and PKM2 mRNA levels were increased in comparison to the corresponding normal tissues, while HIF-1alpha mRNA levels were not significantly changed. The majority of the colorectal cancers demonstrated p53 immunoreactivity, presumably due to mutation of the gene; there was, however, no correlation between the p53 staining pattern and mRNA expression levels of glycolytic enzymes.

Animals↗

PubMed1996

The plastocyanin binding domain of photosystem I.

The molecular recognition between plastocyanin and photosystem I was studied. Photosystem I and plastocyanin can be cross-linked to an active electron transfer complex. Immunoblots and mass spectrometric analysis of proteolytic peptides indicate that the two negative patches conserved in plant plastocyanins are cross-linked with lysine residues of a domain near the N-terminus of the PsaF subunit of photosystem I. Conversion of these negative to uncharged patches of plastocyanin by site-directed mutation D42N/E43Q/D44N/E45Q and E59Q/E60Q/D61N respectively, reveals the first patch to be essential for the electrostatic interaction in the electron transfer complex with photosystem I and the second one to lower the redox potential. The domain in PsaF, not found in cyanobacteria, is predicted to fold into two amphipathic alpha-helices. The interacting N-terminal helix lines up six lysines on one side which may guide a fast one-dimensional diffusion of plastocyanin and provide the electrostatic attraction at the attachment site, in addition to the hydrophobic interaction in the area where the electron is transferred to P700 in the reaction center of photosystem I. This two-step interaction is likely to increase the electron transfer rate by more than two orders of magnitude in plants as compared with cyanobacteria. Our data resolve the controversy about the function of PsaF.

Amino Acid Sequence↗

PubMed1994

EFFECTS OF AMMONIA LOADING ON PORCELLIO SCABER: GLUTAMINE AND GLUTAMATE SYNTHESIS, AMMONIA EXCRETION AND TOXICITY

The effects of ammonia loading in the terrestrial isopod Porcellio scaber were studied by exposing animals to atmospheres of high PNH3. Isopods show a remarkable tolerance of elevated ambient PNH3, with an LD50 of 89 Pa for a 7-day exposure. However, haemolymph total ammonia concentrations generally remained below 5 mmol l-1 (PNH3=0.37 Pa) over the range of ambient ammonia levels used (6.6165 Pa). Following a 7-day loading period, whole-animal glutamine (Gln) and glutamate (Glu) levels increased in direct proportion to ambient PNH3, reaching values of 35 µmol g-1 fresh mass for glutamine and 12 µmol g-1 fresh mass for glutamate in 99 Pa PNH3; these correspond to control levels of 7.5 µmol g-1 fresh mass and 5.9 µmol g-1 fresh mass, respectively. Following transfer to ammonia-free chambers, NH3 excretion rates were augmented five- to sixfold relative to non-loaded controls. Ammonia volatilization subsequently declined, approaching control levels after 89 days. Levels of Gln and Glu showed a concomitant decline to 13.7 µmol g-1 fresh mass and 9.2 µmol g-1 fresh mass, respectively. The results suggest that these amino acids function in ammonia sequestration and, hence, detoxification. Calculations indicate that mobilization of amino groups by deamination of accumulated Gln and Glu could explain 35 % of the increased ammonia production. Implications of NH3 volatilization for acidbase balance are discussed.

Journal Article↗