Biomedical subjects

B Bauer

Publications and source records attributed to B Bauer.

At least 19 recordsLinked to original sources

PubMed2000

The 30-Hz flicker cone ERG for monitoring the early course of central retinal vein occlusion.

PURPOSE: Investigation of the full-field ERG (electoretinography) within 24 hours after the onset of symptoms in central retinal vein occlusion, and repeated examination within the following days and weeks. METHODS: Seven patients with central retinal vein occlusion were examined with full-field ERG within less than 24 hours after the onset of their symptoms and every second to third day during the first 3 weeks. They were then followed for a period of time of six months. RESULTS: The amplitudes as well as the implicit times in the 30 Hz flicker ERG changed considerably within the first three weeks. In the three patients who developed rubeosis, the cone b-wave implicit times as well as the amplitudes were altered considerably. In the patients that did not develop rubeosis, the cone b-wave implicit times as well as the amplitudes in the 30 Hz flicker ERG were more stable. CONCLUSION: The full-field cone ERG reflects the retinal function and the ERG parameters change considerably during the first weeks after the onset of the central retinal vein occlusion. The 30 Hz flicker ERG gives important information concerning the early development of the disease. The optimal time to do a predictive ERG could be after three weeks.

Aged↗

PubMed2000

Loss of Cmk1 Ca(2+)-calmodulin-dependent protein kinase in yeast results in constitutive weak organic acid resistance, associated with a post-transcriptional activation of the Pdr12 ATP-binding cassette transporter.

Yeast cells display an adaptive stress response when exposed to weak organic acids at low pH. This adaptation is important in the spoilage of preserved foods, as it allows growth in the presence of weak acid food preservatives. In Saccharomyces cerevisiae, this stress response leads to strong induction of the Pdr12 ATP-binding cassette (ABC) transporter, which catalyses the active efflux of weak acid anions from the cytosol of adapted cells. S. cerevisiae cells lacking the Cmk1 isoform of Ca2+-calmodulin-dependent protein kinase are intrinsically resistant to weak acid stress, in that they do not need to spend a long adaptive period in lag phase before resuming growth after exposure to this stress. This resistance of the cmk1 mutant is Pdr12 dependent and, unlike with wild-type S. cerevisiae, cmk1 cells are capable of performing Pdr12-specific functions such as energy-dependent cellular extrusion of fluorescein and benzoate. However, they have neither higher PDR12 gene promoter activity nor higher Pdr12 protein levels. The increased Pdr12 activity in cmk1 cells is therefore caused by Cmk1 exerting a negative post-transcriptional influence over the activity of the Pdr12 ABC transporter, a transporter protein that is constitutively expressed in low-pH yeast cultures. This is the first preliminary evidence that shows a protein kinase, either directly or indirectly, regulating the activity of a yeast ABC transporter.

ATP-Binding Cassette Transporters↗

PubMed2000

Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry.

The significance of benzodiazepine receptor (BZR) concentration in comparison with hippocampal metabolism and volumetry was assessed in 14 patients diagnosed with temporal lobe epilepsy (TLE) without hippocampal signal change on T2-weighted magnetic resonance imaging (MRI) scans. Focus lateralization was achieved by clinical, electroencephalographic and neuropsychological examinations. Three-dimensional positron emission tomography (PET) and MRI scans were coregistered for determination of hippocampal 11C-flumazenil (FMZ) binding, normalized to average cortical values for glucose metabolism (rCMRglc) and volume. The hippocampi were individually outlined on T1-weighted MRI. Volumes of interest (VOI) were used for calculation of asymmetries between clinically affected and unaffected sides. Eleven out of 14 TLE patients presented a significant reduction in hippocampal volume. In nine of these 11 patients hippocampal FMZ binding and in seven cases hippocampal CMRglc was also reduced. In two patients without hippocampal volume asymmetry FMZ binding was markedly reduced in the mesial temporal lobe appropriately to the clinically diagnosed side. In our study volumetry is therefore the most sensitive tool for the detection of hippocampal abnormality in TLE. However, in cases without hippocampal atrophy the reduction of FMZ may indicate functional impairment of BZR before neuronal loss becomes evident. Our results emphasize the complementary nature of these tests in TLE patients.

Adult↗

PubMed2000

Early [(11)C]Flumazenil/H(2)O positron emission tomography predicts irreversible ischemic cortical damage in stroke patients receiving acute thrombolytic therapy.

BACKGROUND AND PURPOSE: Central benzodiazepine receptor ligands, such as [(11)C]flumazenil (FMZ), are markers of neuronal integrity and therefore might be useful in the differentiation of functionally and morphologically damaged tissue early in ischemic stroke. We sought to assess the value of a benzodiazepine receptor ligand for the early identification of irreversible ischemic damage to cortical areas that cannot benefit from reperfusion. METHODS: Eleven patients (7 male, 4 female, aged 52 to 75 years) with acute, hemispheric ischemic stroke were treated with alteplase (recombinant tissue plasminogen activator; 0.9 mg/kg according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms. At the beginning of thrombolysis, cortical cerebral blood flow ([(15)O]H(2)O) and FMZ binding were assessed by positron emission tomography (PET). Those early PET findings were related to the change in neurological deficit (National Institutes of Health Stroke Scale) and to the extent of cortical damage on MRI or CT 3 weeks after the stroke. RESULTS: Hypoperfusion was observed in all cases, and in 8 patients the values were below critical thresholds estimated at 12 mL/100 g per minute, comprising 1 to 174 cm(3) of cortical tissue. Substantial reperfusion was seen in most of these regions 24 hours after thrombolysis. In 4 cases, distinct areas of decreased FMZ binding were detected. Those patients suffered permanent lesions in cortical areas corresponding to their FMZ defects (112 versus 146, 3 versus 3, 2 versus 1, and 128 versus 136 cm(3)). In the other patients no morphological defects were detected on MRI or CT, although blood flow was critically decreased in areas ranging in size up to 78 cm(3) before thrombolysis. CONCLUSIONS: These findings suggest that imaging of benzodiazepine receptors by FMZ PET distinguishes between irreversibly damaged and viable penumbra tissue early after acute stroke.

Aged↗

PubMed1999

Phospholipase D stimulation by receptor tyrosine kinases mediated by protein kinase C and a Ras/Ral signaling cascade.

Stimulation of phospholipase D (PLD) in HEK-293 cells expressing the M(3) muscarinic receptor by phorbol ester-activated protein kinase C (PKC) apparently involves Ral GTPases. We report here that PKC, but not muscarinic receptor-induced PLD stimulation in these cells, is strongly and specifically reduced by expression of dominant-negative RalA, G26A RalA, as well as dominant-negative Ras, S17N Ras. In contrast, overexpression of the Ras-activated Ral-specific guanine nucleotide exchange factor, Ral-GDS, specifically enhanced PKC-induced PLD stimulation. Moreover, recombinant Ral-GDS potentiated Ral-dependent PKC-induced PLD stimulation in membranes. Epidermal growth factor, platelet-derived growth factor, and insulin, ligands for receptor tyrosine kinases (RTKs) endogenously expressed in HEK-293 cells, apparently use the PKC- and Ras/Ral-dependent pathway for PLD stimulation. First, PLD stimulation by the RTK agonists was prevented by PKC inhibition and PKC down-regulation. Second, expression of dominant-negative RalA and Ras mutants strongly reduced RTK-induced PLD stimulation. Third, overexpression of Ral-GDS largely potentiated PLD stimulation by the RTK agonists. Finally, using the Ral binding domain of the Ral effector RLIP as an activation-specific probe for Ral proteins, it is demonstrated that endogenous RalA is activated by phorbol ester and RTK agonists. Taken together, strong evidence is provided that RTK-induced PLD stimulation in HEK-293 cells is mediated by PKC and a Ras/Ral signaling cascade.

Bacterial Proteins↗

PubMed1999

Cognitive processing is involved in cluster headache but not in chronic paroxysmal hemicrania.

BACKGROUND: Cognitive processing in migraine is characterized by a loss of habituation during the interval and increased latencies in an attack. No studies are available on event-related potentials (ERPs) in cluster headache or chronic paroxysmal hemicrania. OBJECTIVE: To determine the involvement of cognitive processing in cluster headache and chronic paroxysmal hemicrania as measured by ERPs. METHODS: Visually evoked ERPs were measured in 50 patients with episodic cluster headache, 11 patients with chronic cluster headache, and 12 patients with chronic paroxysmal hemicrania. Measurements were performed in the cluster period outside an attack with and without prophylactic medication and not in the cluster period. RESULTS: Latencies of the endogenous ERP components were significantly increased during the cluster period as compared with outside the cluster period and with healthy subjects. In chronic cluster headache, latencies of both endogenous and exogenous components were increased. Medication with prophylactic drugs normalized the ERP latencies in episodic cluster headache; in chronic cluster headache, ERP latencies were decreased without complete normalization. No changes of ERP latencies and amplitudes could be observed in chronic paroxysmal hemicrania. A loss of cognitive habituation as it is known in migraine could not be observed in either cluster headache or chronic paroxysmal hemicrania. CONCLUSIONS: Our data suggest that central structures generating ERPs are involved in the pathophysiology of cluster headache during the cluster period but not outside the cluster period. This is in concordance with recent neuroimaging findings on the central role of the hypothalamus and the right frontal cortex in cluster headache and supports the hypothesis of a central origin of cluster headache. Furthermore, the data suggest that cluster headache and chronic paroxysmal hemicrania are distinct entities.

Adult↗

PubMed1999

Cellular mechanisms of infarct size reduction with ischemic preconditioning. Role of calcium?

Brief episodes of ischemia protect or "precondition" the heart and reduce infarct size caused by a subsequent sustained ischemic insult. Despite a decade of intensive investigation, the cellular mechanism(s) responsible for this paradoxical protection remain poorly understood. In this review, we focus on the emerging concept that alterations in intracellular calcium homeostasis may participate in either triggering and/or mediating infarct size reduction with preconditioning.

Animals↗

PubMed1999

Effector recognition by the small GTP-binding proteins Ras and Ral.

The Ral effector protein RLIP76 (also called RIP/RalBP1) binds to Ral.GTP via a region that shares no sequence homology with the Ras-binding domains of the Ser/Thr kinase c-Raf-1 and the Ral-specific guanine nucleotide exchange factors. Whereas the Ras-binding domains have a similar ubiquitin-like structure, the Ral-binding domain of RLIP was predicted to comprise a coiled-coil region. In order to obtain more information about the specificity and the structural mode of the interaction between Ral and RLIP, we have performed a sequence space and a mutational analysis. The sequence space analysis of a comprehensive nonredundant assembly of Ras-like proteins strongly indicated that positions 36 and 37 in the core of the effector region are tree-determinant positions for all subfamilies of Ras-like proteins and dictate the specificity of the interaction of these GTPases with their effector proteins. Indeed, we could convert the specific interaction with Ras effectors and RLIP by mutating these residues in Ras and Ral. We therefore conclude that positions 36 and 37 are critical for the discrimination between Ras and Ral effectors and that, despite the absence of sequence homology between the Ral-binding and the Ras-binding domains, their mode of interaction is most probably similar.

ATP-Binding Cassette Transporters↗

PubMed1999

Functional identification of alpha 1-giardin as an annexin of Giardia lamblia.

A protein with a relative molecular mass of 31 kDa was specifically extracted by EGTA from a detergent-insoluble fraction of Giardia lamblia. N-terminal sequencing showed this protein to be identical to alpha 1-giardin, a component of the ventral disc which, based on its predicted amino acid sequence, has been classified as annexin XIX. Purified alpha 1-giardin associated with multilamellar phosphatidyl serine-containing vesicles in a Ca(2+)-dependent manner, confirming that it is a functional annexin. Molecular modelling of the amino acid sequence of the giardial annexin into the X-ray structure of annexin V suggests that the Ca(2+)-binding sites, which, as in other annexins, are all located on the convex surface of the molecule, are of the low-affinity type III.

Amino Acid Sequence↗

PubMed1999

A drug incubation Glossina infectivity test (DIGIT) to assess the susceptibility of Trypanosoma congolense bloodstream forms to trypanocidal drugs (Xenodiagnosis).

Blood was collected from two Sahelian goats, experimentally infected with either a drug-sensitive cloned population of Trypanosoma congolense (IL 1180) or a multiple drug-resistant T. congolense stock (Samorogouan/89/CRTA/267) and incubated at 37 degrees C for 30 min and 12 h, respectively, in the presence of different drug concentrations (0.5, 1.0, 10.0 and 100.0 microg/ml blood) of diminazene aceturate or isometamidium chloride. After that, the trypanosome/blood/drug suspensions were offered to tsetse flies (2100 teneral Glossina morsitans submorsitans) through an in vitro feeding system, using a silicone membrane. All tsetse flies were dissected and examined for the presence of trypanosomes in labrum, hypopharynx and midgut 20 days after their infective blood-meals. Infectivity of the drug-sensitive cloned population was already completely abolished after incubation with 0.5 microg/ml of both drugs; however, 13.6-42.2% of tsetse having been fed on untreated blood had developed an infection. In contrast, no significant differences were observed in the infection rates between the experimental groups and their control groups when fed on blood infected with the multiple drug-resistant stock after incubation for 30 min with up to 10 microg/ml of diminazene or isometamidium. In consequence, tsetse appear to be a useful tool in the assessment of drug susceptibility of typanosome populations.

Animals↗

PubMed1999

Polymerase chain reaction characterization of trypanosomes in Glossina morsitans submorsitans and G. tachinoides collected on the game ranch of Nazinga, Burkina Faso.

The polymerase chain reaction was used to characterize the trypanosomes infecting Glossina morsitans submorsitans and G. tachinoides in the game ranch of Nazinga, Burkina Faso, situated near an agropastoral zone. Dissection of 435 tsetse flies, and PCR analysis of 166 infected flies were conducted to assess the epidemiological situation. Trypanosomes of the Nannomonas subgenus were the most abundant in the two tsetse species (80.4% and 73.7% of identified infections in G. m. submorsitans and G. tachinoides respectively). T. vivax and T. brucei infection rates were comparable between the two tsetse species. Mature infection pattern identified by PCR differed from overall infections, mainly because T. simiae infections did not mature, whereas T. vivax represented the predominant taxon. Parasitological and PCR results showed some discrepancies; possibly some typical Duttonella strains could not be recognized by the sets of primers used. The technologies used in this work helped to determine the high trypanosomosis risk in this area.

Animals↗

PubMed1999

Protein kinase Ctheta, a selective upstream regulator of JNK/SAPK and IL-2 promoter activation in Jurkat T cells.

The predominant expression of protein kinase C (PKC) theta in T cells (J. Biol. Chem. 1993. 268: 4997-5004), its isoenzyme-specific ability to stimulate AP-1 transcriptional activity (Mol. Cell. Biol. 1996. 16: 1842-1850) and the recent discovery of its selective and antigen-dependent colocalization with the contact region between T cells and antigen-presenting cells (Nature 1997. 385: 83-89) suggest that, among the PKC family members, PKCtheta plays a specialized role in T cell activation. By investigating the downstream effectors of PKCtheta we now demonstrate a direct and isoenzyme-specific contribution of PKCtheta to c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not extracellular regulated kinase (ERK) activation. Expression of a constitutively active (CA) form of PKCtheta (but not CA-PKCalpha, epsilon and lambda/iota) resulted in strong activation of JNK/SAPK and expression of a dominant-negative form of PKCtheta interfered with the endogenous activation signal for JNK/SAPK. Importantly, Ca2+ ionophore and CA-PKCtheta (but not CA-PKCalpha, epsilon and lambda/iota) caused synergistic activation of the IL-2 promoter. Together, these data establish that PKCtheta is required for activation of JNK/SAPK signaling leading to IL-2 promoter transcription in T lymphocytes.

Anisomycin↗

PubMed1999

Synergistic action of protein kinase C theta and calcineurin is sufficient for Fas ligand expression and induction of a crmA-sensitive apoptosis pathway in Jurkat T cells.

Deletion of activated peripheral T cell clones by apoptosis requires the regulated expression of Fas ligand (FasL) and sensitization of these cells to CD95-mediated signaling. To investigate the signaling pathways responsible for FasL expression in T cells, we tested-besides subfamily-selective protein kinase C (PKC) inhibitors - the effect of constitutively active mutants of representatives of all PKC subfamilies, i.e. PKCalpha,epsilon,theta,iota, on FasL luciferase promoter reporter constructs. In synergy with a constitutively active form of protein phosphatase 2B calcineurin (CaN), only PKCtheta, but not PKCalpha,epsilon,iota, preferentially induced FasL promoter reporter activity and, consequently, FasL protein expression in Jurkat T cells. Activation of an inducible PKCtheta AE-estrogen receptor fusion mutant led to a CaN-dependent and rapid FasL reporter activity detected as early as 4 h after addition of 4-hydroxytamoxifen, incidating a direct effect of PKCtheta action on FasL expression. Consistently, in Jurkat T cells, expression of PKCtheta AE / CaN significantly enhanced FasL protein expression and apoptosis in a CD95-dependent manner since cell death was not observed in T cells co-expressing the caspase-8 inhibitor crmA. Taken together, our results support the notion that PKCtheta and CaN are sufficient to regulate apoptosis through FasL expression.

Antigens, Polyomavirus Transforming↗

PubMed1999

[Psychosocial handicap due to chronic headaches. Evaluation of the inventory of Disabilities caused by Headache].

Chronic primary headache has a considerable impact on the quality of life. To date, this impact has been evaluated by measurements of the general pain specific impairment of the quality of life. Headache specific measurements of quality of life or of disability caused by the headache are still missing for the German language. In America, a headache specific questionnaire, the "Headache Disability Inventory" (HDI), has been evaluated which is used in the presented study to create a German version, the "Inventar zur Beeinträchtigung durch Kopfschmerzen" (IBK). 94 consecutive patients with a primary headache disorder (59 female, 35 male; mean age 40 +/- 12 years) were examined. Cronbach's alpha was a = 0.90, the test-retest-reliability after three months was r = 0.87. An analysis of subscales for emotional and functional disability showed similar values for the internal consistency and the test-retest-reliability of these subscales. The scores of the different headache types did not differ significantly. In post-hoc-analyses, however, cluster headache showed higher disability scores than migraine both in the total scale and in the subscales. The total score of the IBK was significantly correlated with the number of headache days per month (r = 0.41; p < 0.0003) but not with the duration of disease or other demographic parameters. The IBK is the first German headache specific measurement of certain aspects of the quality of life in chronic headache patients. It can be used in clinical settings to evaluate the current state of the patient or to monitor treatment and it can be used for scientific studies.

Adult↗

PubMed1999

The impact of ergotamine-induced headache and ergotamine withdrawal on information processing.

Ergotamine abuse and subsequent ergotamine-induced headache is a common problem in the pharmacological treatment of migraine and other headache types; often, withdrawal therapy is necessary. This study investigated whether ergotamine abuse affects information processing and whether withdrawal therapy can lead to an improvement of information processing. We designed a standardized neurophysiological retrospective (ergotamine abuse) and prospective (ergotamine withdrawal) study in a supraregional headache outpatient clinic. Seventy-one patients abusing ergotamine derivatives with subsequent daily headache were enrolled and compared to 36 migraine patients without ergotamine intake and 36 healthy subjects. Information processing was evaluated by latencies and amplitudes of visually evoked event-related potentials (ERP) before and after ergotamine withdrawal therapy. P3 latency of the ERP was significantly increased in ergotamine abuse (442 +/- 45 ms) versus migraine (415 +/- 40 ms) and healthy subjects (410 +/- 33 ms), there was no difference between ergotamine tartrate and dihydroergotamine abuse. The migraine specific loss of habituation in information processing as measured by P3 latency could not be observed in migraine patients with ergotamine abuse. After successful withdrawal therapy in 36 patients, the abnormally prolonged P3 latency was significantly shortened (452 +/- 47 ms versus 433 +/- 30 ms; P < 0.004). Our findings imply that information processing is impaired by ergotamine abuse and can be improved but not normalized after withdrawal therapy. Furthermore, our data provide strong evidence that ergotamine, besides its peripheral effects, has a central mode of action.

Adrenergic alpha-Agonists↗

PubMed1999

[Decisions and attitudes in treatment of incompetent, chronically ill, aged patients. A comparison between nurses and physicians: why does no one ask the nurse?].

Health care decision making in incompetent severely ill patients presents many difficult medical, ethical, and legal problems for the physician. At the same time nurses represent the group of medical professionals who have the closest contact with the patient and who have to carry out most of the decisions and instructions. Treatment decisions and their determinants have been assessed by means of a questionnaire based on three case scenarios offering three different levels of available information of the patient's wishes (no information, DNR-order, advance directive). Responses of 191 doctors and 182 nurses have been analyzed. In both groups ethical factors and patient wishes were regarded as the most important. With an increasing level of information about the patient's will the compliance increased in both groups, being more pronounced among the nurses. The more important the will of the patient was estimated, the less difficult were the decisions, the less aggressive was the treatment level chosen, the less frequent rescuscitation was made, and the more helpful the information on patient's will were experienced. These important relationships occurred mainly in the nurses. Furthermore, age and level of dementia were related with the decisions though with less importance. The more legal aspects were regarded the more aggressive treatment options were chosen. Hospital cost were less important and did not influence the decision making. The results indicate that a more frequent use of advance directives would foster patient autonomy and at the same time lessen the burden on the medical staff. A comprehensive education of both the medical professions and the general public seems warranted.

Adolescent↗

PubMed1999

Preconditioning-induced cardioprotection and release of the second messenger inositol (1,4,5)-trisphosphate are both abolished by neomycin in rabbit heart.

The mechanisms responsible for infarct size reduction with preconditioning remain controversial. Our aim was to determine whether release of the second messenger inositol (1,4,5)-triphosphate (Ins(1,4,5)P3) during the preconditioning stimulus may play a role. To test this concept, Langendorff-perfused rabbit hearts underwent sham perfusion, 5 min of coronary artery occlusion (CO), or 5 min of CO + infusion of neomycin, an agent which inhibits formation of Ins(1,4,5)P3. Direct quantitation (by competitive binding assay) revealed a 2-fold increase in Ins(1,4,5)P3 content with brief ischemia vs shams (0.69 +/- 0.14 vs 0.34 +/- 0.05 pmol/mg tissue; p < .05) that was blocked by neomycin (0.15 +/- 0.04 pmol/mg). Infarct size (by tetrazolium staining) was assessed in additional hearts that underwent 30 min of sustained CO and 2 h of reperfusion. As expected, two 5-min episodes of preconditioning ischemia reduced infarct size versus controls (30 +/- 6% versus 63 +/- 3% of the myocardium at risk; p < .01). In contrast, infarct size was comparable (54-56% of the risk region) in neomycin-treated control and preconditioned hearts. These results demonstrate that myocardial Ins(1,4,5)P3 content is increased in response to brief preconditioning ischemia and are consistent with the concept that Ins(1,4,5)P3 may be a potential mediator of infarct size reduction with preconditioning in isolated rabbit heart.

Animals↗

PubMed1999

A retrospective long-term analysis of the epidemiology and features of drug-induced headache.

Drug-induced headache is well known to result from the abuse of compounds taken for the treatment of primary headache. The features of drug-induced headache depend on various features including the availability of drugs, the regional health system, and psychogenic factors of the patients. We performed a retrospective study on a series of 257 consecutive German patients presenting with drug-induced headache during the period 1983-1996. Our aim study was to evaluate the demographic features, the frequency of various drugs used, in particular of ergotamine derivates, and changes in these features during the study period. The frequency of drug-induced headache among all headache patients was 8%, with a female preponderance of 81%. Drug-induced headache occurred in all age groups, predominantly in migraine patients (35%). The mean number of substances used was 2.7, mainly, acetaminophen (47.9%), ergotamine tartrate (45%), and combined analgesics (56%). We did not find a significant difference between the associations with ergotamine tartrate and dihydroergotamine, although the latter was taken less frequently. Comparing the early and late years of our study period, there were no changes in the frequency of drug-induced headache (8% versus 7%), although changes in the frequency of some drugs changed (barbiturates, ergotamine tartrate, and codeine intake decreased whereas nonsteroidal anti-inflationary drugs, combined analgesics, and sumatriptan intake increased). Our data suggest that changes in drug availability and the introduction of classification criteria and treatment recommendations did not have a major impact on the frequency of drug-induced headache.

Adult↗