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Biomedical subjects

B Bauer

Publications and source records attributed to B Bauer.

At least 73 records · Page 4Linked to original sources
PubMed1999

QUASIMEME laboratory performance study of the biological effects of tributyltin (imposex and intersex) on two marine gastropod molluscs.

The disruption of the endocrine systems of gastropod molluscs and consequential physiological changes (imposex and intersex) are used as biomarkers for environmental contamination by tributyltin compounds. The first international laboratory performance study on the determination of imposex and intersex in neogastropod molluscs, Nucella lapillus and Littorina littorea has been undertaken by the QUASIMEME (Quality Assurance of Information for Marine Environmental Monitoring in Europe) project. Samples of live gastropods were distributed and participants were asked to record shell height and sex, together with penis length and vas deferens sequence stage (VDS) in Nucella or the intersex stage (IS) and prostate length in Littorina. Calculations were made of vas deferens sequence index (VDSI) and the relative penis size index (RPSI) in Nucella and of intersex stage index (ISI) and the average female prostate length (FPrL) in Littorina. Thirteen (87%) of the 15 participating laboratories returned data. The remaining two laboratories asked to participate in later exercises. For Nucella, seven laboratories reported sex ratios significantly different from the reference laboratory data. Differences in penis length measurements between laboratories were largely random, although there were indications of systematic errors affecting the data from three laboratories. Seven laboratories reported satisfactory data (Z-score magnitude of Z < 2) for VDSI. The inclusion of a high proportion of sub-adults in the Nucella samples may have made separation of the sexes more difficult than in mature adults. The sub-adults will have had smaller pene than mature adults in the same population, and therefore any errors (random or systematic) in the measurement of penis length or observation of reproductive organs would have a potentially greater impact on the final reported values of the summary imposex indices. The Littorina sample did not show a high degree of intersex (ISI = 0.41). The laboratories could determine the sex of Littorina reliably and only one laboratory reported data significantly different from the reference laboratory. All except two laboratories reported satisfactory data for ISI.

Animals↗
PubMed1999

Comparison of commercial ELISA test kits from Australia and the USA with the serum neutralization test in cell cultures for the detection of antibodies to the infectious laryngotracheitis virus of chickens.

The objective of this work was the evaluation under our conditions of two commercial ELISA kits for the detection of antibodies to avian infectious laryngotracheitis (ILT) virus, one from Australia (Trop-ELISA, TropBio) and one from the USA (ProFLOK-ELISA, KPL), and to compare their performance with the conventional serum neutralization test (SNT) in chick embryo liver cells. Repeatability varied considerably, particularly when using the Trop-ELISA. Therefore, if individual results are important, at least two parallel measurements per serum sample are recommended. In 89.3% of the sera tested by SNT, results of two parallel measurements did not vary by more than one 2-fold dilution step. There was good linear correlation between both ELISAs and the SNT, the correlation coefficient for the Trop-ELISA being r = 0.758 and for the ProFLOK-ELISA r = 0.867. The negative/positive cut-off was redefined to suit our conditions. Sera with a SN titre of > or = 1:4 were considered positive. Sera with < or = 15% absorption in the ProFLOK-ELISA were considered clearly negative. For the Trop-ELISA, extinctions of > or = 0.477 were considered positive, < or = 0.168 clearly negative. Values in between were regarded as doubtful for young chickens and as possibly due to non-specific reactions in older chickens. The sensitivity and specificity of the ELISAs relative to the SNT were 87 and 77% for the Trop-ELISA, and 95 and 60%, respectively, for the ProFLOK-ELISA. However, the results indicate that the sensitivity of the ELISA is higher than that of the SNT, because most sera showed similar deviations from SNT results with both ELISAs. Generally, both ELISAs were a suitable alternative to the SNT under our conditions, as long as only negative/positive results are required.

Journal Article↗
PubMed1999

Drug-induced headache: long-term results of stationary versus ambulatory withdrawal therapy.

Drug-induced headache is a well-known complication of the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with drug-induced headache according to the International Headache Society criteria. Out of 257 patients with the diagnosis of drug-induced headache during the study period, 101 patients (41 after ambulatory and 60 after stationary withdrawal therapy) could be followed up for 5.9 +/- 4.0 years. The total relapse rate after successful withdrawal therapy was 20.8% (14.6% after ambulatory and 25.0% after stationary withdrawal therapy, p < 0.2). The main risk factors for a relapse were male sex (OR = 3.9, CI = 1.3-11.6), intake of combined analgesic drugs (OR = 3.8, CI = 1.4-10.3), administration of naturopathy (OR = 6.0, CI = 1.2-29.3), and a trend to tension-type headache as the primary headache disorder (OR = 1.9, CI = 0.6-53.0). Our data suggest that neither the method of withdrawal therapy nor the kind of analgesic and other antimigraine drugs has a major impact on the long-term result after successful withdrawal therapy. Patients with risk factors according to our findings should be informed and monitored regularly, and combined drugs should be avoided. Furthermore, our data suggest that there is a need for research on individual psychological and behavioral risk factors for relapse after successful withdrawal therapy in drug-induced headache.

Adult↗
PubMed1999

Novel membrane-targeted ERK1 and ERK2 chimeras which act as dominant negative, isotype-specific mitogen-activated protein kinase inhibitors of Ras-Raf-mediated transcriptional activation of c-fos in NIH 3T3 cells.

Expression of constructs encoding fusion proteins of ERK1 and ERK2 containing a C-terminal farnesylation motif (CAAX) is predominantly localized at the cell membrane and was activated by coexpression of constitutively active Ha-RasL61 and epidermal growth factor. Both fusion proteins significantly inhibit the transcriptional activation of a c-fos-chloramphenicol acetyltransferase reporter induced by RasL61, constitutively active MEK1, or constitutively active RafBXB. The corresponding SAAX chimeras or overexpression of the wild-type ERKs did not interfere with the transcriptional activation of c-fos. The inhibition of the Ras-mediated c-fos induction by ERK2-CAAX can in part be rescued by coexpression of a wild-type ERK2 but not by wild-type ERK1. We find that ERK1-CAAX acts in the same fashion, indicating that mitogen-activated protein kinase (MAPK)-CAAX chimeras interact in an isotype-specific manner. It is demonstrated that both ERK1-CAAX and ERK2-CAAX associate with the corresponding endogenous ERKs, which explains the isotype-specific inhibitory effects of the ERK-CAAX chimeras. Evidence is presented that expression of ERK-CAAX fusion proteins inhibits the nuclear translocation of the corresponding endogenous ERKs. Disruption of MAPK translocation by membrane targeting provides additional, independent proof that nuclear translocation of ERKs is essential for the transcriptional activation of c-fos.

3T3 Cells↗
PubMed1999

Antihypertensive profiles with ascending dose combinations of ramipril and felodipine ER.

The aim of the study was to identify the most appropriate dosage combination of ramipril and felodipine ER (an extended release tablet) for mild-to-moderate hypertension. Hypertensive patients (N = 507) with supinediastolic blood pressure (DBP) values between 100-115 mm Hg were included in a randomized, multicenter, double-blind study of 3x4 factorial design with a 2-4 week single-blind, placebo run-in and 6 week active treatment phase. The patients were randomized to 12 groups: placebo, ramipril (2.5, 5, 10 mg), felodipine ER (5, 10 mg), or ramipril-felodipine ER combinations (2.5/5 mg, 2.5/10 mg, 5/5 mg, 5/10 mg, 10/5 mg, 10/10 mg). Although the greatest reductions in blood pressure were observed with ramipril-felodipine ER (10/10 mg), consideration of the antihypertensive efficacy and safety factors suggest that the ramipril-felodipine ER (5/5 mg) combination has the best efficacy/tolerability ratio of the combinations tested. The incidence of adverse events with ramipril-felodipine ER combination therapy was similar to that with felodipine ER monotherapy, but peripheral edema, tachycardia and vasodilatation occurred less frequently with ramipril-felodipine ER (5/5 mg) combination than with felodipine ER monotherapy. The combination of ramipril-felodipine ER (5/5 mg) can be considered to be the most suitable option for hypertensive patients with an inadequate response to either of the monocomponents.

Adult↗
PubMed1998

Structure determination of the Ras-binding domain of the Ral-specific guanine nucleotide exchange factor Rlf.

Ral-specific guanine nucleotide exchange factors RalGDS, Rgl, and Rlf have been suggested to function as intermediates between Ras and Ral pathways by being able to bind Ras proteins through their C-terminal Ras-binding domains (RBD). The RBDs of RalGDS and of the Ser/Thr kinase c-Raf-1 have been shown to have the same tertiary structure. In contrast to the RBDs of Raf and RalGDS, which bind either Ras or Rap with high affinity, Rlf-RBD has a similar affinity for both GTP-binding proteins. To be able to compare these RBDs on a structural level, we have solved the three-dimensional structure of Rlf-RBD by NMR spectroscopy. The overall tertiary structure of Rlf-RBD shows the betabetaalphabetabetaalphabeta-fold of the ubiquitin superfamily and is very similar to that of RalGDS-RBD. The binding interface of Rlf-RBD to Ras was mapped using chemical shift analysis and indicated a binding mode similar to that in the case of Rap.Raf-RBD. However, comparison of the putatively interacting regions revealed structural differences which are proposed to be responsible for the different substrate affinities of Rlf-, RalGDS-, and Raf-RBD.

Amino Acid Sequence↗
PubMed1998

Specific inhibition of phorbol ester-stimulated phospholipase D by Clostridium sordellii lethal toxin and Clostridium difficile toxin B-1470 in HEK-293 cells. Restoration by Ral GTPases.

Activation of m3 muscarinic acetylcholine receptor (mAChR), stably expressed in human embryonic kidney (HEK)-293 cells, leads to phospholipase D (PLD) stimulation, a process apparently involving Rho GTPases, as shown by studies with Clostridium botulinum C3 exoenzyme and Clostridium difficile toxin B (TcdB). Direct activation of protein kinase C (PKC) by phorbol esters, such as phorbol 12-myristate 13-acetate (PMA), also induces PLD stimulation, which is additive to the mAChR action and which is only poorly sensitive to inactivation of Rho proteins by TcdB. To study whether Ras-like GTPases are involved in PLD regulation, we studied the effects of the TcdB variant TcdB-1470 and Clostridium sordellii lethal toxin (TcsL), known to inactivate Rac and some members of the Ras protein family, on PLD activities. TcdB-1470 and TcsL did not affect basal PLD activity and PLD stimulation by mAChR or direct G protein activation. In contrast, PMA-induced PLD stimulation was inhibited by TcdB-1470 and TcsL in a time- and concentration-dependent manner, without alteration in immunologically detectable PKC isozyme levels. In membranes of HEK-293 cells pretreated with TcdB-1470 or TcsL, basal and stable GTP analog-stimulated PLD activities measured with exogenous phosphatidylcholine, in the presence or absence of phosphatidylinositol 4,5-bisphosphate, were not altered. In contrast, pretreatment with TcdB-1470 and TcsL, but not TcdB, strongly reduced PMA-stimulated PLD activity. The addition of recombinant Rac1, serving as glucosylation substrate for TcdB, TcsL, and TcdB-1470, did not restore PLD stimulation by PMA. Furthermore, PMA-stimulated PLD activity, suppressed by prior treatment with TcdB-1470 or TcsL, was not rescued by the addition of recombinant Ras (RasG12V) or Rap proteins, acting as glucosylation substrates for TcsL only (Ras) or TcdB-1470 and TcsL (Rap). In contrast, the addition of recombinant Ral proteins (RalA and RalB), glucosylation substrates for TscL and TcdB-1470, but not for TcdB, to membranes of TcdB-1470- or TcsL-treated cells fully restored PLD stimulation by PMA without altering the strict MgATP dependence of PMA-induced PLD stimulation. RalA-mediated restoration of PMA-stimulated PLD activity in membranes of TcsL-treated cells was not enhanced by coaddition of RasG12V. In conclusion, the data presented indicate that TcdB-1470 and TcsL selectively interfere with phorbol ester stimulation of PLD and suggest an essential role of Ral proteins in PKC signaling to PLD in HEK-293 cells.

3T3 Cells↗
PubMed1998

Cone b-wave implicit time as an early predictor of rubeosis in central retinal vein occlusion.

PURPOSE: To investigate the predictive value of the cone b-wave implicit time in the 30-Hz flicker electroretinogram for rubeosis in the acute phase of central retinal vein occlusion. METHODS: In a prospective study, 25 patients (25 eyes) with a central retinal vein occlusion of less than 14 days' duration were examined with electroretinography and followed up for a minimum of 18 months. RESULTS: The cone b-wave implicit time in the eyes that developed rubeosis (n = 11) was more than 37.1 milliseconds and in the eyes that did not develop rubeosis (n = 14), less than 37 milliseconds (P < .00001). CONCLUSION: The cone b-wave implicit time in the 30-Hz flicker electroretinogram is a good predictor of rubeosis at an early stage in eyes with central retinal vein occlusion.

Acute Disease↗
PubMed1998

Analysis of genomic rearrangement and subsequent gene deletion of the attenuated Orf virus strain D1701.

The orf virus (OV) strain D1701 belongs to the genetically heterogenous parapoxvirus (PPV) genus of the family Poxviridae. The attenuated OV D1701 has been licensed as a live vaccine against contagious ecthyma in sheep. Detailed knowledge on the genetic structure and organization of this PPV vaccine strain is an important prerequisite to reveal possible genetic mechanisms of PPV attenuation. The present study demonstrates a genomic map of the approximately 158 kbp DNA of OV D1701 established by hybridization studies of cloned restriction fragments covering the complete viral genome. The results show an enlargement of the inverted terminal repeats (ITR) to up to 18 kbp due to recombination between nonhomologous sequences during cell culture adaptation. DNA sequencing of the region adjacent to the ITR junction revealed the absence of one open reading frame designated E2L. In contrast to a transposition-deletion variant of the New Zealand OV strain NZ2 (Fleming et al., 1995) the two genes E3L (a homologue of dUTPase) and G1L neighbouring E2L are retained in OV D1701. DNA and RNA analyses proved the presence of E2L gene in wild-type OV isolated directly from scab material. The data presented indicate that the E2L gene is nonessential for virus replication in vitro and in vivo, and may represent one important viral gene in determining virulence and pathogenesis of OV.

Amino Acid Sequence↗
PubMed1998

Fluorescein angiography versus ERG for predicting the prognosis in central retinal vein occlusion.

PURPOSE: It is not easy to predict which patients with a central retinal vein occlusion will develop rubeosis and which will not. We have compared two methods for doing so, fluorescein angiography and full-field electroretinogram (ERG). Our aim was to improve our possibilities for predicting rubeosis in patients with central vein occlusion. METHODS: 32 patients with a central retinal vein occlusion with a duration of less than 14 days were included in the study. Fluorescein angiography and ERG were performed in all patients. The fluorescein angiograms were studied by two independent examiners in a masked mode. The patients were then followed for at least one year. RESULTS: Development of rubeosis in patients with central retinal vein occlusion could be predicted by fluorescein angiography in 82% of the patients and with ERG in 94% of the patients. The non-ischemic central retinal vein occlusions were identified in 62% by fluorescein angiography and in 100% with ERG. Fluorescein angiography misjudged 9 patients 28%, whereas ERG only misjudged 1 patient, 3%. CONCLUSION: ERG seems to be a better method for predicting the prognosis in central retinal vein occlusion than fluorescein angiography.

Adult↗
PubMed1998

Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity.

Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.

Adenocarcinoma↗
PubMed1998

Host preferences of tsetse (Diptera: Glossinidae) based on bloodmeal identifications.

An enzyme-linked immunosorbent assay (ELISA) was developed to identify the origin of vertebrate blood in the guts of 29 245 wild-caught flies of eleven Glossina species from various ecological zones of Africa. Depending on the quality of the bloodmeal samples, 62.8% of the samples were identified and could be assigned to a host-group (e.g. ruminant), family (e.g. Bovidae) or species (e.g. Bos spp.). A total of 13 145 samples (44.9%) was identifiable up to the species level. With a few exceptions, the present results are in agreement with earlier published reports. Glossina austeni and G. fuscipleuris seemed to have a distinct feeding preference for Suidae (mainly bushpig). Glossina morsitans ssp. fed mainly on Suidae (mainly warthog), although local variations were observed and in some areas hippopotamus or ruminants replaced the warthog as the main host. Bushbuck seemed to be the principal food source for G. longipalpis and G. fusca. Glossina pallidipes fed mainly on ruminants (buffalo, bushbuck and cattle) but, depending on host availability and location, Suidae were also important hosts. Hippopotamus was identified as the main source of bloodmeals for G. brevipalpis. The main hosts for G. longipennis were Suidae (mainly bushpig) and not rhinoceros as had been reported 40 years earlier. The opportunistic feeding behaviour of the palpalis tsetse group was confirmed. The results showed that changes in environment, fauna and host availability may result in modification of tsetse feeding patterns.

Animals↗
PubMed1998

Peripheral autonomic potentials in primary headache and drug-induced headache.

Autonomic functions of different primary headache types have been investigated in several studies, most of them analyzing cardiovascular reflex mechanisms or biochemical changes. The results are contradictory; only in tension-type headache and in cluster headache has a sympathetic hypofunction been shown in a preponderance of studies. We analyzed the peripheral autonomous potentials (PAPs) in different primary headache types and in drug-induced headache and compared the results with those of healthy subjects and of patients with low back pain. Latencies of PAPs were significantly increased in all headache types but not in low back pain; amplitudes of PAPs did not show significant differences compared to healthy subjects. Patients with a long duration of drug abuse had increased PAP latencies, whereas patients with a high number of migraine attacks per year had decreased latencies. Our data suggest that sympathetic hypofunction as measured by PAP latencies is a general phenomenon in headache but not in all pain syndromes. Drug abuse leads to an increase of this hypofunction. While measuring PAPs is not an appropriate method by which to differentiate between headache disorders, it allows assessment of autonomic disturbances in primary and drug-induced headache.

Adult↗
PubMed1998

Activation of the small GTPase Ral in platelets.

Ral is a ubiquitously expressed Ras-like small GTPase which is abundantly present in human platelets. The biological function of Ral and the signaling pathway in which Ral is involved are largely unknown. Here we describe a novel method to measure Ral activation utilizing the Ral binding domain of the putative Ral effector RLIP76 as an activation-specific probe. With this assay we investigated the signaling pathway that leads to Ral activation in human platelets. We found that Ral is rapidly activated after stimulation with various platelet agonists, including alpha-thrombin. In contrast, the platelet antagonist prostaglandin I2 inhibited alpha-thrombin-induced Ral activation. Activation of Ral by alpha-thrombin could be inhibited by depletion of intracellular Ca2+, whereas the induction of intracellular Ca2+ resulted in the activation of Ral. Our results show that Ral can be activated by extracellular stimuli. Furthermore, we show that increased levels of intracellular Ca2+ are sufficient for Ral activation in platelets. This activation mechanism correlates with the activation mechanism of the small GTPase Rap1, a putative upstream regulator of Ral guanine nucleotide exchange factors.

ATP-Binding Cassette Transporters↗
PubMed1998

Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke.

BACKGROUND AND PURPOSE: Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since gamma-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [11C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas. METHODS: In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke. RESULTS: In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO2 (<60 micromol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow. CONCLUSIONS: These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.

Aged↗
PubMed1998

Event-related potentials (P300) in primary headache in childhood and adolescence.

There is strong evidence for a loss of habituation during cognitive processing in migraine as measured by P300 and contingent negative variation in adults. Event-related potentials evoked by an oddball paradigm have not yet been studied in children and adolescents suffering from different primary headache types. We recorded visually evoked event-related potentials (two consecutive trials, 200 stimuli each) in 48 children and adolescents suffering from migraine without or with aura, from episodic tension-type headache, and from ergotamine-induced headache and analyzed the latencies, amplitudes, and reaction times. No statistically significant differences were noted between all headache types and healthy controls analyzing the averaged parameters for the whole measurement. However, a highly significant loss of cortical habituation as measured by P300 amplitude and latency could be observed in migraine without and with aura by analyzing the first and the second trial of measurement separately. This phenomenon increased with age and could not be seen in healthy controls, or patients with tension-type headache or ergotamine-induced headache. Our data suggest a specific cognitive processing in migraine even in children and adolescents. Measurement of the habituation effect in P300 latency and amplitude provides a specific method to differentiate between primary headache types in childhood and adolescence.

Adolescent↗
PubMed1998

11C-methionine PET for differential diagnosis of low-grade gliomas.

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

Adult↗