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Biomedical subjects

J Kraus

Publications and source records attributed to J Kraus.

At least 55 records · Page 3Linked to original sources

An optimized probe set for the detection of small interchromosomal aberrations by use of 24-color FISH.

The rapid spread of the use of new 24-color karyotyping techniques has preceded their standardization. This is best documented by the fact that the exact resolution limits have not yet been defined. Indeed, it is shown here that a substantial proportion of interchromosomal aberrations will be missed by all multicolor karyotyping systems currently in use. We demonstrate that both the sensitivity and the specificity of 24-color karyotyping critically depend on the fluorochrome composition of chromosomes involved in an interchromosomal rearrangement. As a solution, we introduce a conceptual change in probe labeling. Seven-fluorochrome sets that overcome many of the current limitations are described, and examples of their applications are shown. The criteria presented here for an optimized probe-set design and for the estimation of resolution limits should have important consequences for pre- and postnatal diagnostics and for research applications.

Chromosome Aberrations↗

[Generalized brain edema in non-purulent meningoencephalitis. The anti-edema effect of therapy with dexamethasone].

We report about two female inpatients aged 58 and 24, suffering from non-purulent meningoencephalitis, in the first case caused by varizella-zoster-virus, in the second case probably due to viral infection. Both patients developed a diffuse brain edema associated with a progressive loss of consciousness. The adjunctive treatment with dexamethasone led to rapid improvement of clinical symptoms. Computed tomography revealed a significant reduction of brain edema. These results of these two cases support the efficacy of corticosteroids as adjunctive treatment of diffuse brain edema caused by non-purulent meningoencephalitis. The pathophysiological mechanisms are discussed.

Adult↗

Morphine self-administration in mu-opioid receptor-deficient mice.

Morphine-induced place preference was demonstrated recently in wild-type mice, whereas this conditioned behaviour was not observed in mu-opioid receptor-deficient mice. In the present study, we investigated locomotor effects of subcutaneously (s.c.) injected morphine as well as intracerebroventricular (i.c.v.) morphine self-administration in mu-opioid receptor-knockout mice. After s.c. morphine injection, locomotor activity significantly increased in wild-type animals. As expected, in the self-administration test the rate of self-administration constantly increased in wild-type mice reflecting reward effects of morphine. This increase was independent of locomotor/motor activity. In contrast, self-administration rates and locomotor/motor activity significantly decreased in the receptor-deficient animals. It was shown that this aversive effect might partly be due to kappa-opioid receptor interaction.

Analysis of Variance↗

Interaction of phloretin with membranes: on the mode of action of phloretin at the water-lipid interface.

The interaction of phloretin with single lipid bilayers on a spherical support and with multilamellar vesicles was studied by differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR). The results indicated that phloretin interacts with the lipid layer and changes its structural parameters. In DSC experiments, phloretin in its neutral form strongly decreased the lipid phase transition temperature and slightly reduced the cooperativity of the phase transition within the lipid layer. In NMR measurements, phloretin led to an increase of the transverse relaxation time constant but had no effect on the spin-lattice relaxation time constant. The overall dipole moment of phloretin was experimentally determined and was found to be roughly 40% lower than has been published previously. This result suggested that the size of the dipole moment of phloretin does not provide such a high contribution to the effect of phloretin on the dipole potential of monolayers and bilayers as has been published previously. To understand the discrepancy between phloretin adsorption and dipole potential change, we performed computational conformational analysis of phloretin in the gas phase. The results showed that a wide distribution of the dipole moments of phloretin conformers exists, which mainly depends on the orientation of the OH moieties. The adsorption of phloretin as determined from its binding to solid supported bilayers differed from the one determined from dipole potential measurements on black lipid membranes. The difference between the phloretin dissociation constants of both types of experiments suggested a change of its dipole moment normal to the membrane surface in a concentration-dependent manner, which was in agreement with the results of the computational conformational analysis.

Adsorption↗

Anthraquinones and betaenone derivatives from the sponge-associated fungus Microsphaeropsis species: novel inhibitors of protein kinases.

An undescribed fungus of the genus Microsphaeropsis, isolated from the Mediterranean sponge Aplysina aerophoba, produces two new betaenone derivatives (1, 2) and three new 1,3,6, 8-tetrahydroxyanthraquinone congeners (5-7). The structures of the compounds were established on the basis of NMR spectroscopic and mass spectrometric data and by CD spectroscopy. This is the first report wherein the (1)H and (13)C NMR data of the betaenone congeners are fully and unambiguously assigned on the basis of two-dimensional NMR spectroscopy. Furthermore, we describe the first elucidation of the absolute configuration of 1-(2'-anthraquinonyl)ethanols such as 5 and 6, by quantum chemical calculation of their circular dichroism (CD) and comparison with experimentally measured spectra. Moreover, it was shown that compounds 1, 5, 6, and 7 are inhibitors of PKC-epsilon, CDK4, and EGF receptor tyrosine kinases.

Animals↗

Soluble and cell surface ICAM-3 in blood and cerebrospinal fluid of patients with multiple sclerosis: influence of methylprednisolone treatment and relevance as markers for disease activity.

OBJECTIVE: The expression of intercellular adhesion molecule-3 (ICAM-3), a member of the Ig supergene family, is restricted to immune competent cells. Expression of soluble and cell surface ICAM-3 (s- and c-ICAM-3) is preferentially seen in the state of low activation of the immune system. We studied the relevance of the expression levels of s- and c-ICAM-3 in cerebrospinal fluid (CSF) and blood as markers for disease activity as well as the influence of high-dose methylprednisolone (MP) treatment upon the expression of s- and c-ICAM-3 in blood of patients with multiple sclerosis (MS). MATERIALS AND METHODS: A total of 33 patients (relapses n = 25, remission n = 8) with relapsing-remitting MS were included into the study. CSF and blood were acquired from all of them. Of the patients 24 were treated with high-dose MP. In those, blood was additionally collected at the 10th day of the therapy and after 3 months. Expression of c-ICAM-3 was determined by two colour FACS analysis, whereas the concentration levels of s-ICAM-3 were measured by ELISA. RESULTS: In CSF we detected a significant decrease of the expression levels of c-ICAM-3 on CD3+ T cells in 25 patients suffering from an acute relapse in contrast to 8 patients with remission (P= 0.04). In comparison to the levels before treatment and after 3 months, at the 10th day of MP treatment we obtained highly significant changes of the expression values of c-ICAM-3 both on CD3+ T cells (P = 0.0004; P= 0.005) and CD14+ monocytes/macrophages (P =0.0006; P=0.008) on the 10th day of high-dose MP treatment from 24 MS patients. CONCLUSION: The increase of ICAM-3 levels might indicate the anti-inflammatory effect of the MP treatment. It could be interesting to search for similar effects investigating the new immune modulatoring therapy forms of MS.

Acute Disease↗

Screening for thrombophilic risk factors among 25 German patients with cerebral venous thrombosis.

OBJECTIVES: In this study the frequency of inherited thrombophilic risk factors in a population of German CVT patients and their influence on clinical outcome were evaluated. MATERIAL AND METHODS: Twenty-five patients (age 37.1 +/- 16.3 years) with CVT were screened for inherited coagulation disorders. All participants received a full clinical follow-up (mean follow-up period 4.8 +/- 6.4 years). RESULTS: Inherited thrombophilic risk factors were identified in 9 (36%) of the 25 patients studied. Four were found positive for the heterozygous factor V Leiden mutation, 2 were heterozygous carriers of the prothrombin-G20210A-polymorphism. APC resistance proved to be a reliable screening method for factor V Leiden mutation, whereas genetic evaluation for protein S and C deficiencies failed to demonstrate any mutations despite the identification of 1 patient with a protein C and protein S deficiency each. One patient suffered from a familial plasminogen deficiency. These 9 patients had a less favorable outcome (P < 0.05). CONCLUSION: Our results demonstrate that screening for inherited thrombophilia should be an integral part in the diagnostic work up of CVT patients. Patients with inherited coagulopathies tended to have a less favorable outcome, corroborating recommendations for a longer period of oral anticoagulation.

Adult↗

CD45RA+ ICAM-3+ lymphocytes in cerebrospinal fluid and blood as markers of disease activity in patients with multiple sclerosis.

OBJECTIVES: Autoreactive T cells targeted against antigens of the myelin sheath are suggested to play an important role in the pathogenesis of multiple sclerosis (MS). Naive (CD45RA+) T cells and intercellular adhesion molecule-3 (ICAM-3) are markers for un-activated lymphocytes. This study was performed to investigate, whether the expression levels of these antigens both on cerebrospinal fluid (CSF) and peripheral blood lymphocytes can be used as activity markers in MS. MATERIALS AND METHODS: Corresponding blood and CSF samples were obtained from 31 patients with relapsing-remitting MS. Of the 31 MS patients 23 were suffering from acute relapses at the time of examination and all of them were treated with high-dose methylprednisolone (MP). Blood was collected again on the 10th day of therapy and after 3 months. The control group consisted of 12 healthy persons. Two-color flow cytometry was performed to evaluate the percentage of both CD45RA+ and ICAM-3+ cells within the lymphocyte population. RESULTS: The percentage of CD45RA+ ICAM-3+ cells in the CSF of MS patients with relapses was significantly increased compared to patients in remission (P<0.05). In blood, a significantly lower percentage of CD45RA+ ICAM-3+ lymphocytes was found in both patient groups compared to healthy controls (Relapse: P<0.05, Remission: P<0.10). Additionally, we found a significant increase (P < 0.01) in the percentage of CD45RA+ ICAM-3+ lymphocytes in blood of MS patients suffering from acute relapse on the 10th day of high-dose MP treatment. CONCLUSION: Our data suggest that the percentage of CD45RA+ ICAM-3+ lymphocytes in CSF can be used as marker of disease activity in MS patients.

Acute Disease↗

Regulation of mouse delta-opioid receptor gene transcription: involvement of the transcription factors AP-1 and AP-2.

The aim of this study was to examine the effects of the phorbol ester O-tetradecanoylphorbol 13-acetate (TPA) and forskolin on delta-opioid receptor gene transcription. Treatment of NG108-15 cells with TPA (100 nM) for 48 h increased delta-opioid receptor mRNA levels, whereas different concentrations of forskolin induced a transient down-regulation of mRNA 5 h after treatment, followed by increased mRNA levels after 48 h. Reporter gene assays in transiently transfected NG108-15 cells in combination with electrophoretic mobility shift assays indicate that the increase of delta-opioid receptor mRNA after stimulation with TPA is mediated by transcription factor AP-1, which binds 355 bp upstream of the start codon within the gene promoter. The forskolin-induced mRNA increase is mediated neither by a cyclic AMP-response element nor indirectly by AP-1 up-regulation. Reporter gene assays, mutational analysis, and electrophoretic mobility shift assays revealed that delta-opioid receptor gene regulation by forskolin is mediated by transcription factor AP-2, which binds to an element 157 bp upstream of the start codon.

1-Methyl-3-isobutylxanthine↗

An allelic variation in the human prodynorphin gene promoter alters stimulus-induced expression.

Prodynorphin, the precursor of the dynorphin opioid peptides, has been shown to play an important role in several aspects of human diseases and complex traits, e.g., drug abuse, epilepsy, and mood disorders. The objective of this study was to identify polymorphisms in the 5' control region of the human prodynorphin gene and to relate these polymorphisms to prodynorphin gene expression. Within the core promoter region, a 68-bp sequence was found to occur as a polymorphic element, either singular or as tandemly repeated element two, three, or four times. This 68-bp repeat element contains an AP-1 transcription factor binding site as demonstrated by electrophoretic mobility shift assay. Reporter gene assays were performed and provided evidence for allele dependent different promoter activity. Dynorphin was found to be involved in many pathophysiological processes so that the described prodynorphin alleles may correlate with the occurrence of several diseases, for example, drug addiction. However, prodynorphin allelic distributions were not significantly different in heroin addicts and control subjects.

Alleles↗

Violence and its injury consequences in American movies: a public health perspective.

OBJECTIVES: To evaluate the seriousness and frequency of violence and the degree of associated injury depicted in the 100 top-grossing American films of 1994. METHODS: Each scene in each film was examined for the presentation of violent actions on persons and coded by a systematic context-sensitive analytic scheme. Specific degrees of violence and indices of injury severity were abstracted. Only actually depicted, not implied, actions were coded, although both explicit and implied consequences were examined. RESULTS: The median number of violent actions per film was 16 (range, 0-110). Intentional violence outnumbered unintentional violence by a factor of 10. Almost 90% of violent actions showed no consequences to the recipient's body, although more than 80% of the violent actions were executed with lethal or moderate force. Fewer than 1% of violent actions were accompanied by injuries that were then medically attended. CONCLUSIONS: Violent force in American films of 1994 was overwhelmingly intentional and in 4 of 5 cases was executed at levels likely to cause significant bodily injury. Not only action films but movies of all genres contained scenes in which the intensity of the action was not matched by correspondingly severe injury consequences. Many American films, regardless of genre, tend to minimize the consequences of violence to human beings.

Humans↗

Violence and its injury consequences in American movies: a public health perspective.

OBJECTIVES: The purpose of this study was to evaluate the seriousness and frequency of violence and the degree of associated injury depicted in the 100 top grossing American films of 1994. METHODS: Each scene in each film was examined for the presentation of violent actions upon persons and coded by means of a systematic context sensitive analytic scheme. Specific degrees of violence and indices of injury severity were abstracted. Only actually depicted, not implied, actions were coded, although both explicit and implied consequences were examined. RESULTS: The median number of violent actions per film was 16, with a range from 1 to 110. Intentional violence outnumbered unintentional violence by a factor of 10. Almost 90% of violent actions showed no consequences to the recipient's body, although more than 80% of the violent actions were executed with lethal or moderate force. Fewer than 1% of violent actions were accompanied by injuries that were then medically attended. CONCLUSIONS: Violent force in American films of 1994 was overwhelmingly intentional and in four of five cases was executed at levels likely to cause significant bodily injury. Not only action films but movies of all genres contained scenes in which the intensity of the action was not matched by correspondingly severe injury consequences. Many American films, regardless of genre, tend to minimize the consequences of violence to human beings.

Americas↗

[Reproductive health in women in the Czech Republic 1993-1997. I. Study methodology and characteristics of the sample groups].

AIM OF THE STUDY: To identify changes in reproductive health status as a consequence of changes in the system of health care and social affairs. THE AIM OF THIS PART OF STUDY: To prepare the methodology of data collection and to identify changes of demographic characteristics. TYPE OF THE STUDY: Retrospective comparative epidemiological study. INSTITUTION: Institute for the Care of Mother and Child, Praha 4-Podolí. METHODS: Two nation-wide surveys on reproductive health of representative three-stage cluster samples in 1993 and 1997. After selection of residential sites from all districts the households were selected for interview. One hundred and fifty trained interviewers asked selected women of reproductive age (4,497 in 1993 and 1,735 in 1997) questions according to a special questionnaire. The basic demographic characteristics of the two samples were compared with the 1991 Census data. The 1993 Czech Republic Reproductive Health Survey was funded by the United States Agency for international Development via a WHO agreement; the 1997 Survey was funded by the Czech Statistical Office and Ministry of Health. RESULTS: The age structure is very similar in the 1993 sample and in the 1991 Census data, however, there is a remarkably lower proportion of women 15-19 years of age in the 1997 sample. According to the marital status, the 1997 sample has a higher proportion of women living in partner-strip and divorced women. The 1997 sample has a higher proportion of women with only one child and there were fewer women with 4 and more children. Also the proportion of women with secondary education with higher school certificate was higher in the later sample. CONCLUSION: This part of the study evaluate a changes in four demographic characteristics of women of reproductive age, because these changes could influence the reproductive health indicators (contraception, induced abortions), which are the subject of further analysis.

Adolescent↗

[Reproductive health in women in the Czech Republic 1993-97. II. Contraception].

THE AIM OF THE STUDY: To identify changes in reproductive health status as consequence of changes in the system of health care and social affairs. THE AIM OF THIS PART OF STUDY: To identify changes in use of different contraceptive methods among women of reproductive age in the Czech Republic. TYPE OF THE STUDY: Retrospective comparative epidemiological study. NAME AND ADDRESS OF THE INSTITUTION: Institute for the Care of Mother and Child Praha 4--Podolí. METHODS: Comparison of data on contraceptive use among women of reproductive age from two representative national surveys (see the first part of the study). Analysis was done by demographic characteristics using programs developed by the Centers for Disease Control, Atlanta, Georgia, U.S.A. RESULTS: There was no difference in proportion of women using one of four methods of contraception in 1993 sample and in 1997 sample (60%), however, there was change in their order. While the most frequently used method in 1993 sample was withdrawal (18.6% out of 60% of contraceptive users) and the pills were the last used method (7.7%), the order in 1997 sample was just opposite (pills 23.9%, withdrawal 6.7%). The proportion of condom and IUD users remained practically unchanged. With decline of withdrawal users, the proportion of other three methods increased from 37% to 52% (out of 60% of contraceptive users). The hormonal contraception was preferred method among women with higher education, while condom was the most popular among women with occasional intercourse or women with different partners (single women, women without children, divorced women). CONCLUSION: The withdrawal and condom users were the more frequent methods of contraception in 1993 sample versus two other methods (ratio 2:1), while this has changed in 1997 sample in favor of IUD and hormonal contraception users (ratio 3:2). We could conclude that the responsibility for contraception has been transferred from men to women.

Adolescent↗

Regulation of mouse somatostatin receptor type 2 gene expression by glucocorticoids.

Somatostatin is a regulatory peptide with important inhibitory functions. Its effects are mediated by five receptors, sst1-sst5. Previous studies revealed that sst2 contains three alternative, tissue specific promoters. Here, molecular mechanisms for the regulation of sst2 transcription by glucocorticoids were investigated. Reporter gene assays in NG 108-15 cells and electrophoretic mobility shift assays revealed that a glucocorticoid responsive element at position -1044 on the second promoter mediates dexamethasone induction. These findings, the existence of a cAMP response element and the tissue dependent activity (brain, pituitary and gastrointestinal tissues) indicate the importance of the second sst2 gene promoter.

Animals↗

[Nosocomial pneumonias in a neurology intensive care unit].

BACKGROUND AND OBJECTIVE: Nosocomial pneumonia in patients in an intensive care unit (ICU) are a great problem as a cause of increased morbidity and mortality as well as the resulting high cost of treatment. This study was aimed at determining the incidence of nosocomial pneumonia and the risk factors for its occurrence in patients with severe neurological disease. PATIENTS AND METHODS: Between 1.1. and 31.12.1997, 217 patients (125 men, 92 women; average age 63.4 years) were prospectively included if they were treated for more than 48 hours in the ICU of the Neurology Department of Erlangen University. The occurrence of nosocomial pneumonia (NP) was noted, using the criteria of the Center of Disease Control and Prevention (CDC). Incidence of the diseases was related to age, sex, initial state of consciousness, type of ventilation, duration of stay in the ICU and any associated medical condition. RESULTS: NP was diagnosed in 68 patients (31.4%). Statistically significant relative risks were male sex (2.4 fold, P < 0.01), clouded consciousness with a Glasgow coma score < 8 (6.2 fold, P < 0.001), mechanical ventilation (8.4 fold, P < 0.001), time in ICU > or = 8 days (9.3 fold, P < 0.001) and associated medical condition (3.3 fold, P < 0.005). In 17.7% of cases no relevant pathogen was identified microbiologically. A mixed infection was present in 36.8% of cases. The most common Gram-positive organism was Staph, aureus (35.3%), the most common Gram-negative ones were Ps. aeruginosa (25%), Kl. pneumoniae and Kl. oxytoca (11.8%), E. Coli (10.3%) and Acinetobacter species (7.4%). There was also a high rate of infection or infestation with Candida albicans or glabrata (41.2%). NP played a clinically decisive role in the fatal course of 13 of the 47 patients who died. CONCLUSION: These data (incidence, relative risk) can, by taking into consideration various aspects of specialist and hospital hygienic practices, contribute to a continuing optimization of the prevention and treatment of disease.

Aged↗

Ondine's curse in association with diabetes insipidus following transient vertebrobasilar ischemia.

Ischemic lesions of the brainstem can lead to complex neurologic deficits. Failure of the automatic control of ventilation (Ondine's curse syndrome) is a possible but rare syndrome following localized brainstem dysfunction. We report on a 49-year-old man with intermittent bradycardia, cranial nerves' dysfunctions and a slight right-sided hemiparesis. An acute brainstem ischemia was diagnosed and treated immediately with high-dose heparin. Cerebral angiography revealed a proximal occlusion of the left vertebral artery but a normal right vertebral artery and a hyperplastic right posterior inferior cerebellar artery. Cranial Computed Tomography and MRI scan demonstrated multiple ischemic lesions in the posterior circulation. During a 4-week treatment course the patient underwent six episodes of acute severe hypoxia and hypercapnia requiring orotracheal intubation twice and manual ventilation by air mask over a few minutes for four times after a tracheostomy had been performed. Twice a short-term episode of hypothalamic Diabetes insipidus was observed following hypoventilation. We conclude that both Ondine's curse syndrome and diabetes insipidus were due to transient vertebrobasilar ischemia.

Brain Stem Infarctions↗

Driver compliance with stop signs at pedestrian crosswalks on a university campus.

Pedestrians on college campuses interact continuously with various motorized vehicles. Rates of compliance with stop signs at pedestrian crosswalks and noncomplying vehicles were monitored in spring 1996 on a large urban campus. The number of pedestrians, pedestrian clearance, type of vehicle, hour of day, and day of week were monitored at 3 pedestrian crosswalks. The overall compliance rate for stop signs was 22.8 per 100 vehicles, ranging from 1.4 per 100 for bicycles to 46.2 per 100 for commuter vans. Compliance increased to 53 per 100 vehicles when pedestrians were present in the crosswalk. Several differences in compliance rates were found among the observation sites. Lowest compliance was observed for bicycles and motorcycles. Pedestrians on this and other college campuses risk injuries because of violations of pedestrian right-of-way laws. The problem calls for appreciable educational efforts by college health personnel.

Automobile Driving↗