Biomedical subjects

G Krause

Publications and source records attributed to G Krause.

At least 37 records · Page 2Linked to original sources

PubMed2004

["Emerging infectious diseases". Dengue-fever, West-Nile-fever, SARS, avian influenza, HIV].

Some emerging infectious diseases have recently become endemic in Germany. Others remain confined to specific regions in the world. Physicians notice them only when travelers after infection in endemic areas present themselves with symptoms. Several of these emerging infections will be explained. HIV is an example for an imported pathogen which has become endemic in Germany. SARS and avian influenza are zoonoses with the potential to spread from person to person. Avian influenza in humans provides a possibility for the reassortment of a potential new pandemic strain. Outbreaks of dengue fever in endemic areas are reflected in increased infections in travelers returning from these areas. Currently, West-Nile-virus infections are only imported into Germany. The timely implementation of diagnostic, therapeutic and infection control measures requires physicians to include these diseases in their differential diagnosis. To achieve this goal, good cooperation between physicians, laboratories and the public health service is essential.

Animals↗

PubMed2003

Mitochondrial DNA as a clonal tumor cell marker: gliomatosis cerebri.

The aim of this study was a clonal analysis of gliomatosis cerebri (GC), a rare disease characterized by diffuse, extensively infiltrating glial tumors of the central nervous system. Two females of the series were not informative in assays for X-chromosomal inactivation, and a polycytosine tract of the mitochondrial DNA (mtDNA) was tested as a clonal marker. Following fluorescent PCR, a fraction of human individuals shows several electrophoretic bands in normal tissues, some of which can be lost in corresponding glial tumors. Two male patients of our series fulfilled this prerequisite and were thus informative. In patient 1, four tumor samples from the left temporal and occipital cortex, histologically corresponding to WHO grades III and IV, showed an identical loss of bands, which was not observed in tumor-free brain and in tumors from the left cerebellum, from fornix and corpus callosum, and from the right occipital cortex, corresponding to WHO grades III and IV. Since this patient exhibited a TP53 mutation in exon 7, we sequenced this exon in all tissue samples of this individual. The mutation was found selectively in the tumor samples with a loss of mtDNA bands. In patient 2, all tumors (histologically corresponding to WHO grade II) from putamen, thalamus, midbrain and right parietal cortex exhibited an identical loss of bands in the mtDNA analysis. Taken together, these results support that even distant tumors in a patient with GC can share a common clonal origin. They demonstrate the extraordinary mobility and infiltrative power of these tumor cells.

Biomarkers, Tumor↗

PubMed2003

[First evaluation of the surveillance systems of notifiable diseases under the infectious disease control law in Germany].

INTRODUCTION: The implementation of the infectious disease control law (IfSG) in 1.1.2001 standardised the German surveillance system for notifiable diseases. For management and transmission of reports health departments use either the software programme Surv Net@RKI, which was developed by the Robert Koch-Institut (RKI), or one of five commercially offered disease-reporting software. After more than one year of its existence, we investigated the success of the implementation of the new surveillance system with the aim to identify possibilities for further improvement. METHODS: Based on 2001 data available to the RKI, we evaluated the criteria simplicity (standardisation of legal regulation and of software systems), acceptability (number of reporting regional counties), time (period from data entry at the health department to entry at the RKI) and data quality (information on immunisation status among reports of hepatitis A cases). RESULTS: For electronic processing 5 versions of Surv Net@RKI and 47 versions of the 5 commercial products are used. Additional rules of individual states expand the legal obligation for notification of the IfSG, by adding new diseases, different definitions or different reporting channels. Within the first quarter after implementation of the IfSG, 393 (90 %) of the 425 counties transmitted data weekly. The median transmission time from data entry at the health department and entry at the RKI was 5 to 7 days after the fourth reporting week. The proportion of hepatitis A case reports with information on immunisation status was 58 % (1323 of 2277); among the 1052 reports by health departments using Surv Net@RKI the proportion was 82 % (n = 858); among the 1225 reports from health departments using other programmes the proportion was 38 %. CONCLUSION: Implementation of the new surveillance system is successful. Electronic data systems should be standardised to improve data quality and simplicity. The deadlines for transmission should be shortened to allow earlier detection and control of multi-state outbreaks. State-specific rules on notifiable diseases should be standardised to avoid conflicting or redundant reporting channels.

Communicable Disease Control↗

PubMed2003

[Malaria surveillance in Germany 2000/2001--results and experience with a new reporting system].

In Germany, malaria is one of the most frequently imported infectious diseases. In January 2001, the newly implemented Infektionsschutzgesetz (Law for Protection Against Infectious Diseases) brought some important changes in surveillance case notification procedures. After one year, experience shows that the changes did not affect the continuity and representative nature of malaria reporting in Germany. In the years 2000 and 2001, 836 and 1,040 malaria cases, respectively, were reported. In both years, most of the patients were between 30 and 49 years old. 82 % of the infections had been acquired in Africa, and 11 % in Asia. The predominant parasite species was P. falciparum (70 %), followed by P. vivax (12 % in 2000, and 16 % in 2001, respectively). The majority of infections occurred among tourists, fewer in immigrants or business travellers. About two thirds of all patients had not taken any chemoprophylactics. Compared to previous years a decrease in the number of fatal cases was observed (1998: 21, 1999: 18, 2000: 8, 2001: 8). To ameliorate the situation of imported malaria intensified prevention activities are necessary, including efforts to improve choice and compliance of chemoprophylaxis and to facilitate timely diagnosis and treatment.

Adolescent↗

PubMed2003

[SARS surveillance--did it meet the demands made on the surveillance of new infectious diseases?].

INTRODUCTION: The world-wide outbreak of severe acute respiratory syndrome (SARS) in the spring of 2003 highlighted the importance of reliable surveillance for infectious diseases. The aim of this investigation is to identify possibilities for the improvement of the German surveillance system based on the experiences made during the SARS epidemic 2003. METHODS: The RKI has established two linked databases for the surveillance of SARS, to store case-based data on SARS and to keep a record of inquiries by the public health system. Based on these data we evaluated the information flow for the surveillance of SARS mainly qualitatively. RESULTS AND DISCUSSION: With occurrence of the first SARS case in Germany a nationwide surveillance system for SARS was established. Since Germany was exclusively confronted with imported SARS cases, the surveillance system could fulfil the requirements. It is unclear, however, whether the current procedures are sufficient to manage larger epidemics of emerging diseases. For this task the public health system needs a uniform electronic information management system which allows rapid adaptation to the epidemic situation and is able to deal with a large amount of data.

Databases as Topic↗

PubMed2003

RIONET: a water quality management tool for river basins.

The water quality management tool RIONET for river basins has been developed with regard to the EU Water Framework Directive. The management tool can simulate the water quality in catchment basins not only in the dimension of a single river but in whole river networks. A submodel of the IWA River Water Quality Model No. 1 is used in RIONET. The river model is based on the assumption that self purification processes in the river takes place both in the benthic biofilm and the bulk water phase. Laboratory experiments with sediment cores underline the major role of the benthic biofilm. The input parameters of the management tool such as volumetric flow rates from waste water treatment plants and flow velocities and discharge in the main river and its tributaries can be loaded directly from geographic information systems (GIS). The subcatchment basin of the river Bode in Saxon Anhalt was used for test runs of RIONET.

Biofilms↗

PubMed2002

[Epidemiology and clinical symptomatology of Creutzfeldt-Jakob disease].

OBJECTIVE: Analogous to prospective studies in other countries, prevalance and symptoms of sporadic Creutzfeldt-Jakob disease (CJD) were recorded in order to assess irregularities in the incidence of the disease in Germany since the onset of bovine spongioform encephalopathy (BSE). PATIENTS AND METHODS: SInce 1993 all suspected case of CJD reported in the Federal Republic of Germany have been analysed by a unified schema and classified by standardised criteria. In addition to voluntary reporting two other systems were accessed: (1) compulsory reporting to the Robert Koch Institute via the appropriate Health Department and (2) cause of death statistics of the Federal Office of Statistics. RESULTS: Between June 1993 and May 2001, a total of 1247 patients with suspected CJD, obtained by the angle quotation mark, rightStudy of the epidemiology and early diagnosis of human spongioform encephalopathiesangle quotation mark, left at Göttingen University, were examined. The suspected disease was confirmed by autopsy in 404 cases, the diagnosis of probable CJD was made in 369 cases on the basis of clinical data and additional investigation. At the beginning of the Göttingen Study in 1993 the incidence in Germany was 0.7 per mill. population, while in the year 2000 it had risen to 1.3 per mill. population. Corresponding increases in the number of cases since 1993 have been noted also by the Robert Koch Institute and the Federal Office of Statistics. CONCLUSIONS: The increased incidence can be explained primarily by a decrease in previously unknown cases. Concerted action as part of the Göttingen Study has increased the cooperation of associated clinics. In addition to sporadic cases of CJD, genetic and, more rarely, iatrogenic forms have been seen in Germany. But no cases of new variant CJD have been reported so far.

Adult↗

PubMed2002

In vitro genotoxicity assay of sidestream smoke using a human bronchial epithelial cell line.

Genotoxic effects of air contaminants, such as gaseous or particulate compounds, have been difficult to investigate due to inefficient methods for exposing cell cultures directly to these substances. New cultivation and exposure techniques enable treatment of epithelial cells with sample atmospheres with subsequent in vitro assays, as demonstrated by a new system called CULTEX (CULTEX: patent No. DE 19801763; PCT/EP99/00295), which uses a transwell membrane technique for direct exposure of complex mixtures, for example sidestream cigarette smoke, at the air/liquid interface. The sensitivity and susceptibility of human bronchial epithelial cells to this complex mixture have already been shown for cytotoxic endpoints. In this study, genotoxic effects of sidestream cigarette smoke at different concentrations were assessed using the alkaline comet assay. HFBE 21 cells were exposed for 1 h to clean air, nitrogen dioxide or sidestream smoke. Exposure of the cells to sidestream cigarette smoke induced DNA strand breaks in a dose-dependent manner. The combination of gas phase exposure and the comet assay provides a realistic and efficient model for sensitive detection of DNA strand breaks induced by airborne and inhalable compounds.

Bronchi↗

PubMed2002

Comparison between mitochondrial DNA sequences in low grade astrocytomas and corresponding blood samples.

BACKGROUND/AIMS: To identify somatic mutations in the mitochondrial DNA of glioblastomas, in a previous study the displacement loops of 17 glioblastomas and corresponding blood samples were sequenced and instabilities in repeats or transitions were detected in seven tumours. This study was extended by sequencing 10 DNA samples of diffuse astrocytomas (World Health Organisation grade II) and corresponding blood samples. METHODS: The 10 DNA samples of diffuse astrocytomas and corresponding blood samples were amplified and sequenced using fluorescent nucleotides. RESULTS: No sequence differences were detected, with the exception of a quantitative shift between two genotypes heteroplasmic within the hypervariable region 2, which can be interpreted as mitotic drift. In the glioblastoma series, any particular somatic mutation was usually found in only one tumour. The only frequent alteration was coupled to a mitochondrial germline polymorphism under-represented in the low grade astrocytoma group. Moreover, a single mutation in two patients with secondary glioblastomas had already been detected in diffuse astrocytomas of these individuals. CONCLUSIONS: A lower percentage of mitochondrial DNA mutations in low grade tumours cannot be deduced from these data.

Astrocytoma↗

PubMed2002

Longitudinal study of effects of alcohol use and/or personal exercise on high density lipoprotein cholesterol in aging humans.

Self-controlled alcohol use and/or personal physical exercise is generally believed to be advantageous in extending good health in aging humans. We investigated whether data collected over 31 years in the same subjects (369 men, 75 women) in our Longitudinal Aging Study of humans (1969-2000) showed strong relationship between alcohol and/or physical exercise with High Density Lipoprotein Cholesterol (HDLC). Women s HDLC interactions among age, diet, alcohol use and/or exercise were not found to be statistically significant in our study. Men, however, showed a strong positive statistical significance (p<or= 0.0001) among alcohol, personal physical exercise and HDLC.

Adult↗

PubMed2001

Use of surface plasmon resonance for real-time analysis of the interaction of ZO-1 and occludin.

Surface plasmon resonance (SPR) spectroscopy was applied to study in real time, the interaction between the tight junction proteins ZO-1 and occludin. To imitate the morphology of tight junctions, a cytosolic tail of mouse occludin was immobilised at the sensor and guanylate kinase-like domain (Guk) was allowed to pass over the modified chip surface. The Guk domain of ZO-1 (residues 644-812) was found to bind to the cytoplasmic, carboxy-terminal region of occludin (residues 378-521). This interaction was systematically characterised with respect to the concentrations of both proteins and the binding conditions. Under the given experimental conditions, association and dissociation showed saturation kinetics, with affinity in micromolar range: k(a) = 4.14 +/- 0.52 x 10(3) M(-1) s(-1), k(d) = 3.04 +/- 0.38 x 10(-3) s(-1), K(D) = 639 +/- 51 nM. The results support the hypothesis that the Guk domain of ZO-1 is involved in the recruitment of the transmembrane protein occludin at tight junctions by interacting with the cytosolic carboxy-terminal sequence of occludin, located far from the cell membrane. We demonstrate the use of SPR spectroscopy as an effective approach for characterisation of the interactions of junction proteins.

Amino Acid Sequence↗

PubMed2001

High frequency of mitochondrial DNA mutations in glioblastoma multiforme identified by direct sequence comparison to blood samples.

In an earlier study, we showed that heteroplasmy in the mitochondrial genome of gliomas sometimes occurs in a D-loop polycytosine tract. We extended this study by pairwise comparisons between glioma samples and adjacent brain tissue of 55 patients (50 glioblastomas, 1 astrocytoma WHO grade III, 4 astrocytomas WHO grade II). We used a combination of laser microdissection and PCR to detect and quantify variations in the polycytosine tract. New length variants undetectable in the adjacent brain tissue were observed in 5 glioblastomas (9%). In 2 of these cases, samples from a lower tumor stage (WHO grade II) could be analyzed and revealed the early occurrence of these mutations in both cases. Since the mitochondrial D-loop contains additional repeats and highly polymorphic non-coding sequences, we compared 17 glioblastomas with the corresponding blood samples of the same patients by direct sequencing of the complete D-loop. In 6 of these tumors (35%), instability was detected in 1 or 2 of 3 repeat regions; in 1 of these repeats, the instability was linked to a germline T-to-C transition. Furthermore, of 2 tumors (12%) 1 carried 1 and the other 9 additional transitions. In the latter patient, 6.7 kb of the protein coding mtDNA sequence were analyzed. Six silent transitions and 2 missense mutations (transitions) were found. All base substitutions appeared to be homoplasmic upon sequencing, and 89% occurred at known polymorphic sites in humans. Our data suggest that the same mechanisms that generate inherited mtDNA polymorphisms are strongly enhanced in gliomas and produce somatic mutations.

Adult↗

PubMed2001

Creutzfeldt-Jakob disease after receipt of a previously unimplicated brand of dura mater graft.

BACKGROUND: Iatrogenic Creutzfeldt-Jakob disease (CJD) transmission via dura mater grafts has been reported in many countries. In September 1998, a 39-year-old Colorado woman was reported as having suspected CJD after receiving a dura mater graft 6 years earlier. METHODS: An investigation was initiated to confirm the diagnosis of CJD and assess the possible source of CJD transmission. The authors determined the presence or absence of other known CJD risk factors, checked for epidemiologic evidence of possible CJD transmission via neurosurgical instruments, and evaluated the procedures used in the collection and processing of the graft, including whether the donor may have had CJD. RESULTS: The CJD diagnosis was confirmed in the dural graft recipient by neuropathologic and immunodiagnostic evaluation of the autopsy brain tissue. She had no history of receipt of cadaveric pituitary hormones or corneal grafts or of CJD in her family. The authors found no patients who underwent a neurosurgical procedure within 6 months before or 5 months after the patient's surgery in 1992 who had been diagnosed with CJD. The dura mater was obtained from a 57-year-old man with a history of dysarthria, ataxia, and behavioral changes of uncertain origin. The graft was commercially prepared by use of a process that included treatment with 0.1 N sodium hydroxide and avoided commingling of dura from different donors. CONCLUSIONS: The patient's age, absence of evidence for other sources of CJD, the latent period, and the report of an unexplained neurologic illness in the donor of the dura mater indicate that the graft was the most likely source of CJD in this patient.

Adult↗

PubMed2001

Gliomatosis cerebri: post-mortem molecular and immunohistochemical analyses in a case treated with thalidomide.

Gliomatosis cerebri (GC) is a rare tumor of the central nervous system (CNS) characterized by widespread diffuse infiltration of the brain and spinal cord by neoplastic glial cells. We report the case of a 17-year-old boy with a bioptically diagnosed fibrillary astrocytoma. The administration of thalidomide, which was suggested to be beneficial in the treatment of human cancers, had no substantial clinical effect on our patient. Autopsy studies revealed a diffuse infiltration of the frontal and temporal lobes of the right hemisphere, brainstem, and the leptomeninges covering the whole spinal cord by an astrocytic tumor, which showed features both of low-grade astrocytoma and glioblastoma multiforme. No mutations in the p53 and PTEN tumor suppressor genes were found; immunoreactivities for p53, PTEN, and EGFR could not be detected.

Adolescent↗

PubMed2001

Heterogeneous tissue distribution of a mitochondrial DNA polymorphism in heteroplasmic subjects without mitochondrial disorders.

CONTEXT: Several maternally inherited point mutations of the mitochondrial genome cause mitochondrial disorders, but the correlation between genotype and phenotype remains obscure in many cases. The same mutation may cause various diseases, probably because of a different tissue distribution. OBJECTIVE: To assess the role of random somatic segregation in generating interperson differences by analysis of an apparently neutral polymorphism. DESIGN: Screening of 81 brain samples from subjects without mitochondrial disorders and selection of five necropsy cases showing a high level of heteroplasmy for the polymorphism. MAIN OUTCOME MEASURES: A proportion of various distinct genotypes in the mtDNA pool of the tissues, identified by fluorescent PCR products, representing a short polycytosine tract of variable length in the mitochondrial displacement loop. RESULTS: Differences were found between organs or groups of organs within subjects, pointing towards somatic segregation of mtDNA. In addition, marked differences of this organ distribution occurred between subjects, which cannot be explained by tissue specific selection. CONCLUSIONS: The observed interperson differences can be explained by somatic segregation, which occurs randomly at various developmental stages. Besides tissue specific selection, this process might participate in the distribution of pathogenic mtDNA mutations.

Adolescent↗

PubMed2001

A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation.

A specific H-bonding network formed between the central regions of transmembrane domain 6 and transmembrane domain 7 has been proposed to be critical for stabilizing the inactive state of glycoprotein hormone receptors. Many different constitutively activating TSH receptor point mutations have been identified in hyperfunctioning thyroid adenomas in the lower portion of transmembrane domain 6. Position D633 in transmembrane domain 6 of the human TSH receptor is the only one in which four different constitutively activating amino acid exchanges have been identified. Further in vitro substitutions led to constitutive activation of the TSH receptor (D633Y, F, C) as well as to the first inactivating TSH receptor mutation in transmembrane domain 6 without changes of membrane expression or TSH binding (D633R). Molecular modeling of this inactivating TSH receptor mutation revealed potential interaction partners of R633 in transmembrane domain 3 and/or transmembrane domain 7, presumably via hydrogen bonds that could be responsible for locking the TSH receptor in a completely inactive state. To further elucidate the H-bond network that most likely maintains the inactive state of the TSH receptor, we investigated these potential interactions by generating TSH receptor double mutants designed to break up possible H bonds. We excluded S508 in transmembrane domain 3 as a possible interaction partner of R633. In contrast, a partial response to TSH stimulation was rescued in a receptor construct with the double-substitution D633R/N674D. Our results therefore confirm the H bond between position 633 in transmembrane domain 6 and 674 in transmembrane domain 7 suggested by molecular modeling of the inactivating mutation D633R. Moreover, the mutagenesis results, together with a three-dimensional structure model, indicate that for TSH receptor activation and G protein-coupled signaling, at least one free available carboxylate oxygen is required as a hydrogen acceptor atom at position 674 in transmembrane domain 7.

Adenylyl Cyclases↗

PubMed2001

The large cytoplasmic loop of the glucose transporter GLUT1 is an essential structural element for function.

Alanine scanning mutagenesis and the introduction of deletions and insertions were used to address the role of the large cytoplasmic loop in 2-deoxy-D-glucose (2-DOG) uptake by GLUT1 expressed in Xenopus oocytes. Alanine scanning mutagenesis of 29 amino acid residues that are identical or homologous in GLUT1 to GLUT4 demonstrated that the transport activities of only a few variants were affected. Progressive truncation of the loop by six deletions leaving intact 59 (delta236-241), 49 (delta231-246), 39 (delta226-251), 28 (delta221-257), 18 (delta216-262), or 10 (delta213-267) amino acid residues resulted in a progressive decrease in 2-DOG uptake. Compared with wild-type GLUT1 the uptake rates varied between 33% for the delta236-241 mutant and 4% for the delta213-267 mutant. Insertional mutagenesis using hexaalanine or hexaglycine to fill in the deletion 236D-241L restored 2-DOG uptake to 73% of wild-type GLUT1 in the case of hexaalanine, whereas hexaglycine insertion was without effect. Confocal laser microscopy demonstrated that a deletion of six amino acid residues did not influence the expression level in the plasma membrane (delta236-241 mutant), whereas the plasma membrane fluorescence of the delta213-267 mutant was comparable with that of water-injected Xenopus oocytes. Computer-aided secondary structure prediction of the loop suggested that it consists of a long alpha-helix bundle interrupted or kinked by the highly conserved glycine-233.

Alanine↗

PubMed2001

Marijuana use and social networks in a community outbreak of meningococcal disease.

BACKGROUND: We examined the role of social networks and marijuana smoking in a community outbreak of infections due to Neisseria meningitidis. METHODS: We interviewed all patients and their contacts. Isolates were tested by pulsed field electrophoresis and multilocus enzyme electrophoresis. RESULTS: Nine cases of meningococcal disease occurred in the outbreak; isolates from seven cases with positive cultures were identical. Multiple overlapping social networks were found for case-patients and their contacts. All case-patients were linked by the marijuana-related activities of their contacts. CONCLUSION: Investigation of social networks and marijuana exposure might help identify close contacts of patients with meningococcal disease and help prevent secondary infections.

Adolescent↗