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Biomedical subjects

B Bauer

Publications and source records attributed to B Bauer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Different clinical expressions in two families with Stargardt's macular dystrophy (STGD1).

PURPOSE: To describe the clinical expressions, with emphasis on electrophysiological examinations, in two Swedish families with Stargardt's macular dystrophy (STGD1). METHODS: Two pairs of siblings with STGD1, for whom diagnosis had been confirmed by genetic linkage to the ABCA4 gene region, were examined regarding visual acuity, kinetic perimetry, fundus photography, full-field ERG and multifocal ERG (MERG). Possible disease-causing mutations were screened for by DNA sequencing of selected regions of the ABCA4 gene. RESULTS: All STGD1 patients had visual acuity 0.07-0.1. The two families presented different fundus appearances, MERGs and implicit times on 30 Hz flicker white light full-field ERGs. Genetic analysis revealed one unique sequence variation in exon 19 of the ABCA4 gene, in one allele from the patients of one of the families. This point mutation causes the amino acid substitution T972N in the ABCR protein. CONCLUSION: Two pairs of siblings with STGD1 presented two different expressions of the disease regarding the distribution of the retinal dysfunction. One possible molecular explanation to the different clinical expressions may be the T972N substitution present in the ABCR protein in one of the STGD1 families investigated.

ATP-Binding Cassette Transporters↗
PubMed2001

Ivermectin excretion by isolated functionally intact brain endothelial capillaries.

1. Functionally intact brain endothelial capillaries were isolated from porcine brain. p-Glycoprotein was localized at the lumenal membrane of intact capillaries by immunohistochemistry using a murine monoclonal antibody and a secondary FITC fluorescent labelled anti-mouse IgG. Western blot staining of p-glycoprotein in isolated endothelial cells confirmed the immunohistochemistry. 2. Excretion of the fluorescent labelled anthelmintic drug Ivermectin (BODIPY-Ivermectin) was studied in the isolated brain endothelial capillaries. Drug accumulation in the capillary lumen was visualized by fluorescence confocal laser scanning microscopy and was measured by image analysis. Secretion of BODIPY-Ivermectin into the capillary lumen exhibited characteristics of specific and energy-dependent transport. Steady state lumenal fluorescence intensity averaged 1.6 times cellular fluorescence and was reduced 3--4 times below cellular levels when metabolism was inhibited by NaCN. 3. BODIPY-Ivermectin secretion was inhibited in a concentration-dependent manner by unlabeled Ivermectin. In addition, lumenal but not cellular fluorescence intensity was significantly decreased when capillaries were incubated with PSC-833, Cyclosporin A or Verapamil, all inhibitors of p-glycoprotein. Conversely, unlabelled Ivermectin reduced the p-glycoprotein (Pgp)-mediated secretion of a fluorescent derivative of Verapamil, (BODIPY-Verapamil). 4. BODIPY-Ivermectin secretion was not affected in the presence of Leucotriene C(4) (LTC(4)), a potent inhibitor of multidrug resistance related protein (mrp)-mediated transport processes. In addition, excretion of Fluorescein-Methotrexate, an mrp-substrate, was not inhibited by Ivermectin. 5. Uptake experiments with isolated porcine brain capillary cells showing increased cellular uptake of BODIPY-Ivermectin in the presence of unlabelled drug or PSC-833 supported the findings of a Pgp interaction in intact capillaries. 6. The data are consistent with BODIPY-Ivermectin and Ivermectin being transported across the lumenal membrane of brain capillaries. For the first time Pgp-interaction of Ivermectin at the blood brain barrier is demonstrated on a cellular level in an intact vascular tissue.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the VMD2 gene.

PURPOSE: To describe the clinical phenotype in a family with Best's vitelliform macular dystrophy (BMD) and a new mutation (Val89Ala) in the VMD2 gene. METHODS: The genotype was determined by direct sequence analysis of the individual exons of VMD2. Nine members of a family with BMD were examined. The examination included best-corrected visual acuity, electro-oculography (EOG), fundus examination, and photography. Four of the patients were also examined with full-field ERG and three with multifocal ERG. RESULTS: A T-to-C substitution was identified at position 370 in the cDNA of VMD2, leading to a Val89Ala change in the protein. Six patients, five with the Val89Ala mutation and a nine-year-old boy without the mutation, presented with a pathological Arden ratio on EOG examination. Most of the patients with BMD in this family had an onset of visual failure by the age of 40-50 years. The older patients in the family demonstrated atrophic macular dystrophy. CONCLUSIONS: Patients with BMD and the Val89Ala mutation in the VMD2 gene can present with a phenotype of a mostly late-onset visual failure. These BMD patients, who present with visual failure and macular degeneration in middle age, can be misdiagnosed as being affected with adult-onset macular dystrophies instead of BMD, because the latter is often regarded as a disease of childhood and adolescence.

Adolescent↗
PubMed2001

The changing distribution of two riverine tsetse flies over 15 years in an increasingly cultivated area of Burkina Faso.

Changes in the distribution of two riverine tsetse flies, Glossina tachinoides Westwood and Glossina palpalis gambiensis Vanderplank are described in an agro-pastoral area of Burkina Faso subject to increasing human population pressure and land use change. Two similar entomological surveys (one trap every 100 m, 120 km of river) were conducted in 1981 and 1996. Changes in tsetse distribution were compared to land use changes through high resolution remote sensing imagery (LANDSAT, SPOT). There was a close relationship between proximity of crops relative to riverine forest and the density of Glossina. Where fields encroached on riverine vegetation, tsetse populations declined. Where the geomorphological structure was not well suited to agricultural activity, riverine vegetation and tsetse fly populations were relatively unaffected, even with intense agricultural activity nearby. In contrast, increased human activity and higher cattle densities in the surrounding savannah areas were associated with increased tsetse numbers. The results demonstrated a wide diversity of tsetse distribution and habitat within a few kilometres in an agro-pastoral landscape in West Africa.

Agriculture↗
PubMed2001

[Application of radioactive substances in nuclear medicine research: current trends and radiation exposure of study subjects].

AIM: Analysis of the application of radioactive substances in research in the field of nuclear medicine in human beings and of the resulting radiation exposure to study subjects. METHODS: Assessment of applications for approval submitted in accordance with Paragraph 41 of the Radiation Protection Ordinance, evaluated by the Federal Office for Radiation Protection together with the Federal Institute for Pharmaceuticals and Medical Products, within the period from 1997 to 1999. RESULTS: The focus of the studies on the diagnostic application of radioactive substances in medicine evaluated has, since 1998, shifted from oncological to neurological and psychological aspects, while, at the same time, the number of PET studies increased constantly. The proportion of healthy study subjects included in the diagnostic studies increased from 7 to 22%. The number of therapeutic applications of radioactive substances has, since 1997, undergone a three-fold increase, and in the process of this, the focus of attention lay within the area of radioimmuno-therapy and endovascular brachytherapy. The effective dose was, among up to 49% of the investigated healthy study subjects higher than 5 mSv, and among up to 6% of these subjects was at levels of over 20 mSv. Up to 22% of the patients received, within the scope of diagnostic studies, an effective dose of between 20 and 50 mSv. An exceeding of the 50 mSv limit occurred among up to 3% of the patients. CONCLUSIONS: In spite of the increasing numbers of PET applications, conventional nuclear medicine has maintained its importance in the field of medical research. Further developments in the areas of radiochemistry and molecular biology led to an increase in the importance of radio-immuno therapy. The evaluation of new radiopharmaceuticals and the extension of basic biomedical research, resulted in an increase in the proportion of healthy study subjects included in the studies. The radiation exposure among subjects resulting directly from the studies showed, for the period of evaluation, an overall trend towards reduction.

Humans↗
PubMed2000

Association of increased C-peptide serum levels and testosterone in type 2 diabetes.

Background: The purpose of our study was to investigate the association of C-peptide and steroid hormones in males and females with type 2 diabetes compared to controls. Methods: In 562 subjects, matched for age and body mass index (BMI), 126 female type 2 diabetic patients (known diabetes duration: 7.8+/-0.8 years, HbA(1c): 7.6+/-0.14%), 126 healthy female subjects, 155 male type 2 diabetic patients (known diabetes duration: 6.4+/-0.6 years, HbA(1c): 7.7+/-0.11%), and 155 healthy male controls, C-peptide levels and serum levels of steroid hormones (progesterone, cortisol, DHEAS, estradiol, and testosterone) were measured by immunometric assays. Ratios of steroid hormones were calculated to investigate shifts in steroidogenesis. Results: In female patients, testosterone was significantly higher than in controls (1.7+/-0.1 vs. 1.4+/-0.2 pmol/l; P<0.05), something that was also demonstrated for the ratio of testosterone/estradiol (P<0.05). In male patients, lower levels of testosterone (11.8+/-0.5 vs. 14.3+/-0.5 pmol/l; P<0.05) and higher cortisol levels (257.5+/-9.9 vs. 228.2+/-7.9 µmol/l, P<0.01) were found than in controls. The progesterone/DHEAS ratio (P<0.05) and the progesterone/testosterone ratio (P<0.001) were significantly higher and DHEAS/cortisol significantly lower in type 2 diabetic males than in controls. In a multiple linear regression analysis that controlled for age, BMI, C-peptide, HDL-cholesterol, and HbA(1c), testosterone was significantly and positively correlated with C-peptide levels in female (P<0.05) but not in male type 2 diabetic patients. Conclusions: Testosterone levels were higher in female patients than in controls and correlated with C-peptide levels while testosterone levels were lower in male patients than in controls and showed no correlation with C-peptide. A higher ratio of testosterone/estradiol in type 2 diabetic females and of progesterone/DHEAS and progesterone/testosterone in type 2 diabetic males than in controls may indicate gender-dependent shifts in steroidogenesis. Whether the shifts in steroidogenesis contribute to insulin resistance in diabetic patients should be the subject of further studies.

Journal Article↗
PubMed2000

Generation of recombinant parapoxviruses: non-essential genes suitable for insertion and expression of foreign genes.

Orf virus (OV) is an epitheliotropic poxvirus and belongs to the genus Parapoxvirus (PPV). PPV, especially OV, is regarded as a promising candidate for an expression vector. Among available live vaccines only strain D1701 represents a highly attenuated OV strain with clearly reduced pathogenicity. Therefore, we started to identify potentially non-essential genes or regions of D1701, which might be suitable for insertion and expression of foreign genes. The present contribution reviews some of the progress using the vegf-e (homologue of the mammalian vascular endothelial growth factor) gene locus for the generation of recombinant D1701. The vegf-e gene of D1701 is dispensable for virus growth in vitro and in vivo, and represents a major virulence determinant of OV. It is shown that foreign genes can be inserted and functionally expressed in the vegf-e locus, also leading to the induction of a specific immune response in the non-permissive host. Furthermore, it is reported that adaptation to VERO cells led to the deletion of three further regions of the OV D1701 genome, which seems to be combined with additional virus attenuation in sheep. Molecular analysis of this OV D1701 variant allows the identification of new, potentially non-essential sites in the viral genome.

Animals↗
PubMed2000

T cell expressed PKCtheta demonstrates cell-type selective function.

T lymphocyte stimulation leading to interleukin-2 (IL-2) expression requires activation of protein kinase C (PKC); however, the relevant PKC isoform(s) have not yet been systematically defined. Here we examine seven major T cell expressed PKC isoforms (PKCalpha, delta, epsilon, zeta, nu, theta and iota) and identify PKCtheta to be essential for IL-2 expression (via the critical NF-AT and NF-kappaB enhancer) in Jurkat T cells. Employing a conditionally activated PKCtheta estrogen-receptor fusion mutant, a de novo synthesis-independent transactivation of JNK2 was established. Based on mRNA in situ hybridization to mouse whole body sections, PKCtheta was found to be highly expressed in lymphoid organs but also skeletal muscle and the nervous system. PKCtheta function appears to be cell-type specific, since its isoenzyme-selective function was not observed in ectopic expression studies, employing COS-1 or NIH3T3 cells. These results confirm PKCtheta to be the prime target for the activating effect of phorbol ester in T cell signaling and suggest that gene expression as well as gene function of PKCtheta is strictly controlled by the cell type.

3T3 Cells↗
PubMed2000

In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism.

UNLABELLED: Memory and attention are cognitive functions that depend heavily on the cholinergic system. Local activity of acetylcholine esterase (AChE) is an indicator of its integrity. Using a recently developed tracer for positron emission tomography (PET), C-11-labeled N-methyl-4-piperidyl-acetate (C11-MP4A), we measured regional AChE activity in 4 non-demented subjects, 4 patients with dementia of Alzheimer type (DAT) and 1 patient with senile dementia of Lewy body type (SDLT), and compared the findings with measurements of blood flow (CBF) and glucose metabolism (CMRGlc). Initial tracer extraction was closely related to CBF. AChE activity was reduced significantly in all brain regions in demented subjects, whereas reduction of CMRGlc and CBF was more limited to temporo-parietal association areas. AChE activity in SDLT was in the lower range of values in DAT. Our results indicate that, compared to non-demented controls, there is a global reduction of cortical AChE activity in dementia. KEYWORDS: Dementia, cholinergic system, acetylcholine esterase, positron emission tomography, cerebral blood flow, cerebral glucose metabolism.

Acetates↗
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↗