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Biomedical subjects

B Hauer

Publications and source records attributed to B Hauer.

At least 19 recordsLinked to original sources
PubMed2006

Transient left ventricular dysfunction with apical ballooning (tako-tsubo cardiomyopathy) in Germany.

AIMS: A peculiar type of an acute coronary syndrome is characterised by acute onset of chest pain, STsegment changes, elevated troponin I levels and a transient balloon-like apical left ventricular dysfunction, but without significant coronary artery disease. We sought to assess this syndrome in German patients. METHODS AND RESULTS: A total of 22 females and 1 male with acute transient left ventricular dysfunction were identified during an interval of 2 years and were investigated clinically and angiographically. All patients presented without obstructive coronary artery disease. In 16 patients (70%) ST-segment elevations were observed mimicking acute myocardial infarction, whereas the remaining patients (30%) revealed only negative T waves. Deep negative Twaves were characteristically seen during the course of recovery in all patients. Elevated troponin I levels>2.0 microg/l (upper level of normal) were measured in all patients (mean 18+/-26.5 microg/l, range from 2.2-135.7 microg/l). Creatine kinase rose up to a mean of 282+/-236 IU/l (upper level of normal 180 U/l). Emotional or physical stress situations associated with the onset of the symptoms were observed in 16 patients (70%). Other suspected trigger factors were gastrointestinal infection and in one case a surgical intervention. In four patients a trigger factor could not be identified. Left ventriculography showed an ejection fraction of 53+/-15%. After an interval of 7+/-2 days after the first angiogram, ejection fraction had increased from 48+/-11% to 64+/-11% in eight controlled patients by repeated ventriculography. Coronary spasm with a lumen reduction>75% could be provoked using acetylcholine in 10 of 17 tested patients (59%) with reproduction of the symptoms. Within 14 days the LV dysfunction returned to normal in all patients. The ECG abnormalities disappeared completely as early as 3 months (74%) and were not seen in any patient after 6 months. CONCLUSION: Tako-tsubo cardiomyopathy is not exclusively a Japanese or Northern American phenomenon. Despite increased patient reports the exact underlying cause and pathophysiology of this syndrome remain unclear. However, despite the initial dramatic presentation of this disease the prognosis is good.

Aged↗
PubMed2006

Enantioselective formation and ring-opening of epoxides catalysed by halohydrin dehalogenases.

Halohydrin dehalogenases catalyse the conversion of vicinal halohydrins into their corresponding epoxides, while releasing halide ions. They can be found in several bacteria that use halogenated alcohols or compounds that are degraded via halohydrins as a carbon source for growth. Biochemical and structural studies have shown that halohydrin dehalogenases are evolutionarily and mechanistically related to enzymes of the SDR (short-chain dehydrogenase/reductase) superfamily. In the reverse reaction, which is epoxide-ring opening, different nucleophiles can be accepted, including azide, nitrite and cyanide. This remarkable catalytic promiscuity allows the enzymatic production of a broad range of beta-substituted alcohols from epoxides. In these oxirane-ring-opening reactions, the halohydrin dehalogenase from Agrobacterium radiobacter displays high enantioselectivity, making it possible to use the enzyme for the preparation of enantiopure building blocks for fine chemicals.

Catalysis↗
PubMed2006

[Interferon-gamma assays -- description and assessment of a new tool in the diagnosis of tuberculosis].

Up to now the diagnosis of latent tuberculosis infection (LTBI) was based solely on the tuberculin skin test. However, this method offers neither 100 % sensitivity nor -- and this is in particular due to its cross-reactivity with BCG and environmental mycobacteria -- a 100 % specificity. The demand in Germany for a more reliable in vitro test is currently enhanced by the change from the multipuncture test to the intradermal (Mendel-Mantoux) test and by the uncertainty resulting from the ceased production of the tuberculin previously used in Germany. The manufacturers of immunologic test methods such as the QuantiFERON-TB Gold In-Tube (ELISA assay) and the T SPOT-TB Test (ELISPOT assay), which are based on the Interferon-gamma (IFN-gamma) production of sensitized T lymphocytes, offer their products as possible alternatives. This article explains the function of the IFN-gamma tests and gives an overview of the most recent data, possible indications and the open scientific questions to be investigated by future clinical studies. Although the new test methods have the potential to eventually prevail as an additional helpful diagnostic tool, the authors consider a complete replacement of the tuberculin skin test as premature. The IFN-gamma tests may, however, prove already now to be a useful additional diagnostic method.

Cross Reactions↗
PubMed2006

Tuberculosis and tuberculosis control in European prisons.

OBJECTIVE: Correctional facilities have often been cited as reservoirs for tuberculosis (TB), presenting a potential threat to the general population. Although correctional facilities are recognised as ideal settings for interventions, little is known about the TB epidemiology within them. The purpose of our survey was to collect data on TB in prisons of the WHO European Region and on existing control measures. DESIGN: A questionnaire was sent to 52 EuroTB correspondents asking for 2002 data on the total number of inmates, number of prisoners with TB, resistance rates, screening strategies, monitoring and responsibilities. RESULTS: Twenty-two (42.3%) countries completed the questionnaire. The median TB notification rate was 232 per 100,000 inmates (0-17,808). Prisoners had up to 83.6 times more TB than civilians. The majority (90.9%) of the participating countries reported performing active screening for TB on entry into prison, with a median detection rate of 393/100,000 (42-2362). Of the respondent countries, 81.8% claimed to perform contact investigations and 86.4% to house infectious TB patients separately. CONCLUSION: Although response to this survey was only 42.3% and might be biased by a country's engagement in TB control in prisons, the results highlight the vulnerability of prisoners to TB and emphasise the need for adequate case-finding and containment strategies in prison.

Communicable Disease Control↗
PubMed2005

[Future supply of tuberculin in Germany].

The manufacturers of the only tuberculin available up to now in Germany for intradermal TB tests according to Mantoux, Chiron Vaccines Behring, in 2004 unexpectedly stopped the production of the tuberculin Behring GT (GT="gereinigtes Tuberkulin"-purified protein derivative tuberculin). Only residual stocks were sold during the preceding months. The stocks of GT 10 were already depleted at the beginning of 2005, while there are small supplies left of GT 100 and GT 1000. As a temporary solution, Chiron Vaccines Behring is offering to import the Italian tuberculin Biocine PPD 5 IE lyophil produced by Chiron S.r.l. in Siena. As this is not licensed for sale in Germany, it is necessary to obtain an exceptional prescription (Einzelverordnung) according to section sign 73 (3) of the Federal Law Relating to the Manufacture and Distribution of Medicine (Arzneimittelgesetz, AMG). In the long term, Chiron Vaccines Behring plan to secure the supply of tuberculin in Germany by importing, starting in the summer of 2006, the tuberculin produced by Chiron Vaccines Evans in the UK (PPD Evans). However, these plans involve changing over to a different type of tuberculin twice within a very short period of time. Another problem is the unresolved issue of bioequivalence. Besides the above-mentioned tuberculins produced by Chiron Vaccines, a further possibility would be the import of the tuberculin PPD RT23 SSI of the Statens Serums Institute (Copenhagen/Denmark), which is recommended by the World Health Organization (WHO) as the standard tuberculin and which has already been introduced in several European countries, or of other tuberculins such as Tubersol (PPD CT68), which is used in the US. Together with the Robert Koch Institute (RKI) and the Paul Ehrlich Institute (PEI), the German Central Committee against Tuberculosis (DZK) is striving to find a solution, in view of the urgent need for an uninterrupted supply of tuberculin in Germany for diagnostic purposes and contact tracing. A uniform tuberculin should be used in all German regions as a basis to secure a standardized testing procedure and national comparability of test results. The estimated annual requirement for Germany is two million tuberculin test doses. The Statens Serum Institute is currently evaluating the possibility of licensing PPD RT23 SSI in Germany. Chiron Vaccines Behring communicated that it is not aiming to have the Biocine tuberculin licensed for Germany but intends to apply for a license for the tuberculin PPD Evans. Sanofi Pasteur MSD at this point does not intend to have a tuberculin like Tubersol (PPD CT68) licensed for Germany. Until a licensed tuberculin is again available in Germany, it would be very useful if, especially in settings where stocks of tuberculin are essential (e.g. public health services or hospital dispensaries), an exceptional import license could be obtained.

Commerce↗
PubMed2005

[Tuberculosis in Germany in 2001 and 2002].

The implementation of the new law on infectious diseases in 2001 and the resulting notification of more detailed variables has led to a better knowledge about the epidemiology of tuberculosis (TB) in Germany. 7,515 new cases of active tuberculosis were notified to the Robert Koch Institute in 2001, and 7,684 cases in 2002, corresponding to an incidence of 9.1 (2001) and 9.3 (2002) per 100,000 inhabitants (as per 1 October, 2003). The slight increase in new cases in 2002 is most likely due to under-notification in 2001 because of the new system, considering that the previous decline over many consecutive years is continued according to the incidence for 2003 (8.7/100,000; n = 7,184). In 2001 as well as in 2002 42 % of new TB patients were born outside Germany, and those of foreign nationality have a five-fold higher incidence on the average than German citizens. The lung remains the most affected organ (80 %). 4,230 (2001) and 4,267 (2002) were cases of open, i. e., bacteriologically confirmed, pulmonary tuberculosis potentially contagious to their immediate contacts. The resistance rates are stable in the indigenous population, while patients coming from countries with high resistance rates reflect the situation in their countries of origin. Over two thirds of TB patients in Germany are hospitalized at some point during their disease. The treatment results (78 % on the average in 2001) do not reach the WHO target of 85 %. Approximately 7 % of TB patients in Germany still die because of this infectious disease.

Disease Notification↗
PubMed2005

[The Tuberculosis Rapid Assay from DiaVita - No Alternative to the Tuberculin Skin Test].

New methods for diagnosing active tuberculosis (TB) and/or latent tuberculosis infection have been offered increasingly during recent years, also in Germany. The Tuberculosis Rapid Assay ('Tuberkulose Schnelltest [TB-ST]') from DiaVita is a serologic test method aiming to detect, within a few minutes, tuberculosis-specific antibodies in whole blood or serum of tuberculosis patients. Due to a lack of data, it is, however, hardly possible to assess this test on a scientific basis. With a relatively high specificity (according to DiaVita over 95 %) but inadequate sensitivity (approximately 60 - 80 %), particularly in paucibacillary types of TB, we consider this method of limited value for routine testing. If active TB is strongly suspected, a positive test result may corroborate the tentative diagnosis, whereas a negative test result is not helpful for differential diagnosis considering the great number of false-negative test results to be expected. The greatest value of the test seems to be in bacteriologically confirmed TB, in which however there may be no need for additional diagnostics. The test has not been evaluated, and in our opinion is probably unsuitable for detecting latent TB infection. Data is also lacking for a number of patient groups in urgent need of a reliable alternative to the tuberculin skin test (e. g., immunocompromised patients, children). It is not clear whether this method will find a place in routine TB diagnostics. We therefore cannot recommend this test as a routine diagnostic tool for TB at present.

Diagnosis, Differential↗
PubMed2004

[Recommendations for personal respiratory protection in tuberculosis].

These recommendations of the German Central Committee against Tuberculosis give an overview of the current scientific knowledge on the tuberculosis risk of health service employees and on the risk of infection in individual areas of work. The efficacy of face masks and their benefit in tuberculosis control is discussed. There are no reliable data on the efficacy of face masks in preventing infection with M. tuberculosis, nor can such data be expected in the near future, due to the complex interaction of infection-preventing measures. As rapid case finding, isolation, and immediate, effective treatment of infected patients already greatly diminish the risk of transmission, we consider face masks to be of limited use in reducing this risk. However, they may be beneficial in certain areas of work and in certain situations, particularly in the presence of elevated aerosol concentrations. The benefit of face masks depends largely on their correct application. The choice of a particular type of mask requires knowledge of the current epidemiological situation, and a competent assessment of the risk in the area of work for which it is chosen, taking into account the closeness of contact with potentially infectious tuberculosis patients.

Germany↗
PubMed2004

[Latent tuberculosis infection: recommendations for preventive therapy in adults in Germany].

The immunologic mechanisms of latent tuberculosis (TB) infection are complex and hitherto not completely understood. The lifelong risk of an immunocompetent individual of developing active TB after infection with M. tuberculosis is 5-10 % and highest during the first two years after infection. Various factors may considerably increase the risk of developing active TB, e. g., immunosuppressive disease or immunosuppressive medication. However, the development of active TB may be avoided by preventive chemotherapy, the therapy of choice being isoniazid over a 9-month period. Alternative treatment regimens may be indicated in special cases, but it must be borne in mind that the efficacy of these regimens has not been studied sufficiently while they seem to be less well tolerated than isoniazid monotherapy. The tuberculin skin test is still the only sufficiently documented method to detect latent infection with M. tuberculosis which is also suitable for routine application. This test today should be performed exclusively as described by Mendel and Mantoux. Its sensitivity and specificity depend on the prevalence of tuberculosis infection. It should therefore be restricted to individuals at increased risk of latent TB infection. When interpreting the tuberculin skin test, it is necessary to know whether an individual belongs to one of the defined risk groups or has an elevated risk of developing active TB. Among the risk groups are individuals who may have been infected recently with M. tuberculosis (contacts of contagious TB patients) or in whom other factors increase their risk of developing active TB. The indication for chemotherapy for latent TB infection must be based on a careful individual risk-benefit analysis and, besides patient compliance, requires full information of the patient and careful monitoring during therapy. Before initiating treatment, active TB must always be excluded by the proven methods.

Adult↗
PubMed2002

Enzymatic (R)-phenylacetylcarbinol production in benzaldehyde emulsions.

(R)-Phenylacetylcarbinol [(R)-PAC)] is the chiral precursor for the production of the pharmaceuticals ephedrine and pseudoephedrine. Reaction conditions were improved to achieve increased (R)-PAC levels in a simple batch biotransformation of benzaldehyde emulsions and pyruvate, using partially purified pyruvate decarboxylase (PDC) from the filamentous fungus Rhizopus javanicus NRRL 13161 as the catalyst. Lowering the temperature from 23 degrees C to 6 degrees C decreased initial rates but increased final (R)-PAC concentrations. Addition of ethanol, which increases benzaldehyde solubility, was not beneficial for (R)-PAC production. It was established that proton uptake during biotransformation increases the pH above 7 thereby limiting (R)-PAC production. For small-scale studies, biotransformations were buffered with 2-2.5 M MOPS (initial pH 6.5). High concentrations of MOPS as well as some alcohols and KCl stabilised PDC. A balance between PDC and substrate concentrations was determined with regards to ( R)-PAC production and yields on enzyme and substrates. R. javanicus PDC (7.4 U/ml) produced 50.6 g/l (337 mM) ( R)-PAC in 29 h at 6 degrees C with initial 400 mM benzaldehyde and 600 mM pyruvate. Molar yields on consumed benzaldehyde and pyruvate were 97% and 59%, respectively, with 17% pyruvate degraded and 24% converted into acetaldehyde and acetoin; 43% PDC activity remained, indicating reasonable enzyme stability at high substrate and product concentrations.

Acetone↗
PubMed2002

Ectopic expression of the GABA(A) receptor alpha6 subunit in hippocampal pyramidal neurons produces extrasynaptic receptors and an increased tonic inhibition.

We generated transgenic (Thy1alpha6) mice in which the GABA(A) receptor alpha6 subunit, whose expression is usually confined to granule cells of cerebellum and cochlear nuclei, is ectopically expressed under the control of the pan-neuronal Thy-1.2 promoter. Strong Thy1alpha6 subunit expression occurs, for example, in deep cerebellar nuclei, layer V iscocortical and hippocampal pyramidal cells and dentate granule cells. Ligand binding and protein biochemistry show that most forebrain alpha6 subunits assemble as alpha6betagamma2-type receptors, and some as alpha1alpha6betagamma2 and alpha3alpha6betagamma2 receptors. Electron microscopic immunogold labeling shows that most Thy1-derived alpha6 immunoreactivity is in the extrasynaptic plasma membrane of dendrites and spines in both layer V isocortical and CA1pyramidal cells. Synaptic immunolabeling is rare. Consistent with the alpha6 subunits' extrasynaptic localization, Thy1alpha6 CA1 pyramidal neurons have a five-fold increased tonic GABA(A) receptor-mediated current compared with wild-type cells; however, the spontaneous IPSC frequency and the mIPSC amplitude in Thy1alpha6 mice decrease 37 and 30%, respectively compared with wild-type. Our results strengthen the idea that GABA(A) receptors containing alpha6 subunits can function as extrasynaptic receptors responsible for tonic inhibition and further suggest that a homeostatic mechanism might operate, whereby increased tonic inhibition causes a compensatory decrease in synaptic GABA(A) receptor responses.

Action Potentials↗
PubMed2002

Altered receptor subtypes in the forebrain of GABA(A) receptor delta subunit-deficient mice: recruitment of gamma 2 subunits.

A GABA(A) receptor delta subunit-deficient mouse line was created by homologous recombination in embryonic stem cells to investigate the role of the subunit in the brain GABA(A) receptors. High-affinity [(3)H]muscimol binding to GABA sites as studied by ligand autoradiography was reduced in various brain regions of delta(-/-) animals. [(3)H]Ro 15-4513 binding to benzodiazepine sites was increased in delta(-/-) animals, partly due to an increment of diazepam-insensitive receptors, indicating an augmented forebrain assembly of gamma 2 subunits with alpha 4 subunits. In the western blots of forebrain membranes of delta(-/-) animals, the level of gamma 2 subunit was increased and that of alpha 4 decreased, while the level of alpha1 subunits remained unchanged. In the delta(-/-) forebrains, the remaining alpha 4 subunits were associated more often with gamma 2 subunits, since there was an increase in the alpha 4 subunit level immunoprecipitated by the gamma 2 subunit antibody. The pharmacological properties of t-butylbicyclophosphoro[(35)S]thionate binding to the integral ion-channel sites were slightly altered in the forebrain and cerebellum, consistent with elevated levels of alpha 4 gamma 2 and alpha 6 gamma 2 subunit-containing receptors, respectively.The altered pharmacology of forebrain GABA(A) receptors and the decrease of the alpha 4 subunit level in delta subunit-deficient mice suggest that the delta subunit preferentially assembles with the alpha 4 subunit. The delta subunit seems to interfere with the co-assembly of alpha 4 and gamma 2 subunits and, therefore, in its absence, the gamma 2 subunit is recruited into a larger population of alpha 4 subunit-containing functional receptors. These results support the idea of subunit competition during the assembly of native GABA(A) receptors.

Affinity Labels↗
PubMed2001

Continuous production of (R)-phenylacetylcarbinol in an enzyme-membrane reactor using a potent mutant of pyruvate decarboxylase from Zymomonas mobilis.

The optimization of a continuous enzymatic reaction yielding (R)-phenylacetylcarbinol (PAC), an intermediate of the L-ephedrine synthesis, is presented. We compare the suitability of three pyruvate decarboxylases (PDC), PDC from Saccharomyces cerevisiae, PDC from Zymomonas mobilis, and a potent mutant of the latter, PDCW392M, with respect to their application in the biotransformation using acetaldehyde and benzaldehyde as substrates. Among these, the mutant enzyme was the most active and most stable one. The reaction conditions of the carboligation reaction were investigated by determining initial rate velocities with varying substrate concentrations of both aldehydes. From the resulting data a kinetic model was inferred which fits the experimental data with sufficient reliability to deduce the optimal concentrations of both substrates for the enzymatic process. The results demonstrate that the carboligation is most efficiently performed using a continuous reaction system and feeding both aldehydes in equimolar concentration. Initial studies using a continuously operated enzyme-membrane reactor gave (R)-PAC with a space-time yield of 81 g L(-1). d(-1) using a substrate concentration of 50 mM of both aldehydes. The yield was easily increased by cascadation of enzyme-membrane reactors. The new strategy allows the synthesis of (R)-PAC from cheap substrates in an aqueous reaction system. It thereby overcomes the limitation of by-product formation that severely limits the current fermentative process.

Acetaldehyde↗
PubMed2001

Industrial biocatalysis today and tomorrow.

The use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Biocatalytic processes can now be carried out in organic solvents as well as aqueous environments, so that apolar organic compounds as well as water-soluble compounds can be modified selectively and efficiently with enzymes and biocatalytically active cells. As the use of biocatalysis for industrial chemical synthesis becomes easier, several chemical companies have begun to increase significantly the number and sophistication of the biocatalytic processes used in their synthesis operations.

Catalysis↗
PubMed2001

Targeted disruption of the GABA(A) receptor delta subunit gene leads to an up-regulation of gamma 2 subunit-containing receptors in cerebellar granule cells.

GABA(A) receptors are chloride channels composed of five subunits. Cerebellar granule cells express abundantly six subunits belonging to four subunit classes. These are assembled into a number of distinct receptors, but the regulation of their relative proportions is yet unknown. Here, we studied the composition of cerebellar GABA(A) receptors after targeted disruption of the delta subunit gene. In membranes and extracts of delta-/- cerebellum, [(3)H]muscimol binding was not significantly changed, whereas [(3)H]Ro15-4513 binding was increased by 52% due to an increase in diazepam-insensitive binding. Immunocytochemical and Western blot analysis revealed no change in alpha(6) subunits but an increased expression of gamma(2) subunits in delta-/- cerebellum. Immunoaffinity chromatography of cerebellar extracts indicated there was an increased coassembly of alpha(6) and gamma(2) subunits and that 24% of all receptors in delta-/- cerebellum did not contain a gamma subunit. Because 97% of delta subunits are coassembled with alpha(6) subunits in the cerebellum of wild-type mice, these results indicated that, in delta-/- mice, alpha(6)betagamma(2) and alphabeta receptors replaced delta subunit-containing receptors. The availability of the delta subunit, thus, influences the level of expression or the extent of assembly of the gamma(2) subunit, although these two subunits do not occur in the same receptor.

Animals↗