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Biomedical subjects

A Krämer

Publications and source records attributed to A Krämer.

At least 19 recordsLinked to original sources
PubMed2006

A statistical method for estimating the proportion of cases resulting from cross-transmission of multi-resistant pathogens in an intensive care unit.

Multi-resistant bacteria are an increasing challenge for infection control in hospitals and the proportion of patients newly colonized with multi-resistant bacteria during their hospital stay can be used to assess the effectiveness of infection control measures. Current laboratory methods for estimating this require expensive additional tests. We propose an alternative statistical method to estimate the proportion of cases resulting from transmission in a hospital from the distribution of time intervals between subsequent cases. A prerequisite for the application of this method is the existence of records from regular screening of the patients during their hospital stay, usually performed in intensive care units (ICUs). We describe the method and present an example of its application using records of two multi-resistant pathogens collected in an ICU over a three-year period. The estimated proportion of cases resulting from transmission was 0.73 (95% CI: 0.56-0.90) for meticillin-resistant Staphylococcus aureus and 0.45 (95% CI 0.15-0.75) for imipenem-resistant Pseudomonas aeruginosa. The method proposed here can be used for retrospective evaluation of clinical records in order to evaluate the effectiveness of infection control measures in low endemicity settings.

Cross Infection↗
PubMed2006

Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo.

Cyclin B1 is the regulatory subunit of cyclin-dependent kinase 1 (Cdk1) and is critical for the initiation of mitosis. Accumulating data indicate that the deregulation of cyclin B1 is tightly linked to neoplastic transformation. To study the phenotype and the potential preclinical relevance, we generated HeLa cell lines stably transfected with the plasmids encompassing short hairpin RNA (shRNA) targeting cyclin B1. We demonstrate that the reduction of cyclin B1 caused inhibition of proliferation by arresting cells in G2 phase and by inducing apoptosis. Cells, entering mitosis, were impaired in chromosome condensation and alignment. Importantly, HeLa cells with reduced cyclin B1 were more susceptible to the treatment of small interfering RNA targeting Polo-like kinase 1 (Plk1) and to the administration of the chemotherapeutic agent taxol. Finally, HeLa cells with reduced cyclin B1 showed inhibited tumor growth in nude mice compared to that of control cells. In summary, our data indicate that cyclin B1 is an essential molecule for tumor cell survival and aggressive proliferation, suggesting that the downregulation of cyclin B1, especially in combination with other molecular targets, might become an interesting strategy for antitumor intervention.

Animals↗
PubMed2005

[Does migration from high and intermediate endemic regions increase the prevalence of hepatitis B infection in Germany?].

BACKGROUND AND OBJECTIVE: Germany is one of the low endemic areas for hepatitis B. There are 7,3 million foreign citizens and 3,2 million migrants from the former USSR and Eastern Europe with German roots, the "Resettlers" (Aussiedler), who migrated to Germany mostly from countries with moderate or high HBsAg prevalence. The aim of this study was to determine the HBsAg prevalence in adult foreign citizens and resettlers compared with that among the adult German population. METHODS: Adult foreign citizens and resettlers were categorized according to their country of origin into groups with low, intermediate or high HBsAg prevalence, using data from the WHO. Statistics of the Federal Office for Statistics, the Federal Office for Administration and the Federal Ministry of the Interior were used for the demographic analysis. The number of chronic HBsAg carriers for the different population groups and the whole population was then calculated. RESULTS: 84% of the adult migrant population in Germany migrated from countries with intermediate and high HBsAg endemicity. For 2003 we calculated 503 040 HBsAg carriers in Germany. 42% of these have a migratory background, even though migrants represent only 12.7% of the whole population. The risk for chronic infection with HBsAg is 7.1 (4.8-13.2) for the resettlers and is 4.3 (3.0-8.1) times higher for foreign citizens than for the German population. CONCLUSIONS: These remarkable differences in prevalence make it important that migrants and their close contacts be vaccinated properly, pregnant women be included in screening programs and cases of chronic hepatitis B be treated adequately.

Adult↗
PubMed2005

Structure-function analysis of the U2 snRNP-associated splicing factor SF3a.

Human splicing factor SF3a is a part of the 17 S U2 snRNP (small nuclear ribonucleoprotein), which interacts with the pre-mRNA branch site early during spliceosome formation. The SF3a subunits of 60, 66 and 120 kDa are all required for SF3a function in vitro. Depletion of individual subunits from HeLa cells by RNA interference results in a global inhibition of splicing, indicating that SF3a is a constitutive splicing factor. Structure-function analyses have defined domains necessary for interactions within the SF3a heterotrimer, association with the U2 snRNP and spliceosome assembly. Studies aimed at the identification of regions in SF3a60 and SF3a66, required for proper intracellular localization, have led to a model for the final steps in U2 snRNP biogenesis and the proposal that SF3a is incorporated into the U2 snRNP in Cajal bodies.

Animals↗
PubMed2004

[Health situation of and health service provided for adult migrants--a survey conducted during school admittance examinations].

BACKGROUND: In spite of the increasing numbers of migrants in Germany, only few epidemiological studies have been carried out to investigate the health status of ethnic minorities in Germany. Results from national and international studies on the health of immigrants are inconsistent showing either increased or decreased morbidity in relation to native inhabitants. A survey was undertaken to study the self-reported health status, help-seeking behaviour, and health care utilization among immigrants and Germans. METHODS: 565 adults (276 immigrants and 289 Germans, 97% parents) in Bielefeld, Germany, were interviewed while they accompanied children who attended the pre-school medical examinations. In the analysis descriptive statistics and logistic regression models were used. RESULTS: The self-reported general health status of the study population was good for Germans and immigrants. Germans utilized health care facilities and preventive programmes (e. g. screening programmes) more frequently than immigrants. Furthermore, Germans reported higher levels of satisfaction with health care and a higher level of knowledge about several diseases as compared to immigrants. Logistic regression models indicate that neither migration itself (OR = 0.7, 95% CI = 0.4 - 1.1) nor socio-economic factors (OR for low vs. high social level = 1.2, 95% CI = 0.6 - 2.4) were significantly associated with physical diseases among the study population. CONCLUSIONS: We found no indications that immigrants are less healthy compared to Germans. Further investigations are needed to clarify the differences in patterns of health care utilisation and participation in preventive programmes among Germans and ethnic minorities.

Adult↗
PubMed2004

Using mandatory data collection on multiresistant bacteria for internal surveillance in a hospital.

OBJECTIVES: Multiresistant pathogens cause major clinical problems and considerably increase treatment costs. Since 2001 the Protection Against Infection Act (PIA) obligates hospitals in Germany to the documentation of multiresistant bacteria. We analyzed the use of these data for routine internal surveillance. METHODS: We used standard data collected for the mandatory documentation and studied consecutive diagnoses of Methicillin-resistant Staphylococcus aureus (MRSA) in a 893-bed tertiary level hospital in North Rhine-Westphalia in Germany. Based on the Poisson distribution for the cumulative yearly incidence of MRSA, we defined a threshold level for an outbreak. RESULTS: During a 12-month time period 80 patients were diagnosed with MRSA. The time structure and spatial distribution of different MRSA phenotypes (defined through specific antibiotic resistance patterns) were consistent with the within-hospital transmission. In the two preceding time periods of 12 months each, 15 respectively 8 patients with MRSA were found. The defined alert threshold level for cumulative yearly incidence was crossed in the beginnings of the outbreak. CONCLUSION: Monitoring the mandatory data collected on multiresistant bacteria allows the early detection of accumulations suspect for the within-hospital transmission. This knowledge can be used for a fast reaction and breaking off the transmission chains.

Data Collection↗
PubMed2003

Differences in health complaints among university students from three European countries.

BACKGROUND: The purpose of this research was to assess the prevalence of somatic and psychosomatic health complaints in a cross-national population of university students and to study risk factors associated with health complaints. METHODS: The analysis was based on samples of first-year students from Pamplona (Spain), Bielefeld (Germany), and Kaunas (Lithuania). The total sample included 2343 students. Ten health complaints were measured by a symptom checklist with a self-administered questionnaire. Sociodemographic and lifestyle data were also collected. Factor analysis was employed to develop three complaint scores. RESULTS: Multifactorial logistic regression analysis revealed substantial associations between the factors female gender and psychosocial stress and high levels (>median) of complaint scores. Furthermore, after adjustment for age, sex, and lifestyle variables Lithuanian students were less likely to report gastrointestinal complaints (OR 0.62, CI 0.43-0.90) and neck ache/backache (OR 0.41, CI 0.28-0.61) compared to Spanish students. In addition, German students were less likely to report psychosomatic (OR 0.49, CI 0.35-0.69) and gastrointestinal complaints (OR 0.47, CI 0.34-0.65) than their Spanish peers. CONCLUSIONS: Although the results cannot be generalized to the general population of the respective countries, the different profiles of reported complaints should give rise to special interventions in this young population.

Adolescent↗
PubMed2003

Association between infections and signs and symptoms of 'atopic' hypersensitivity--results of a cross-sectional survey among first-year university students in Germany and Spain.

BACKGROUND: This study assessed the hypothesis that a decreased exposure to childhood infectious diseases is associated with signs and symptoms of 'atopic' hypersensitivity diseases. METHODS: A cross-sectional survey was performed among 1368 Spanish and German first-year university students between 1997 and 1999, including self-administered questionnaire data and serological tests. RESULTS: No association between the disease outcomes and hepatitis A, Helicobacter pylori infection and herpes simplex infection was observed in logistic regression analyses, adjusting for potential confounders (centre, sex, smoking, parental education). In contrast, vaccination against hepatitis B was associated with a decreased risk for the outcomes allergic rhinitis (OR 0.63, 95% CI: 0.42-0.95) and total serum IgE above 100 U/ml (OR 0.56, 95% CI: 0.39-0.81). Conversely, seropositivity to HBc antigen was significantly associated with high total serum IgE (OR 2.04, 95% CI: 1.34-3.06). CONCLUSIONS: Our study partly confirmed and partly contradicted previous evidence and hypotheses, respectively, concerning the role of the infections considered. The observation of a decreased risk in persons vaccinated against hepatitis B warrants further, prospective investigation.

Adolescent↗
PubMed2003

Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma.

Recently, centrosome aberrations have been described as a possible cause of aneuploidy in many solid tumors. To investigate whether centrosome aberrations occur in non-Hodgkin's lymphoma (NHL) and correlate with histologic subtype, karyotype, and other biological disease features, we examined 24 follicular lymphomas (FL), 18 diffuse large-B-cell lymphomas (DLCL), 33 mantle cell lymphomas (MCL), and 17 extranodal marginal zone B-cell lymphomas (MZBCL), using antibodies to centrosomal proteins. All 92 NHL displayed numerical and structural centrosome aberrations as compared to nonmalignant lymphoid tissue. Centrosome abnormalities were detectable in 32.3% of the cells in NHL, but in only 5.5% of lymphoid cells from 30 control individuals (P<0.0001). Indolent FL and MZBCL contained only 25.8 and 28.8% cells with abnormal centrosomes. In contrast, aggressive DLCL and MCL harbored centrosome aberrations in 41.8 and 35.0% of the cells, respectively (P<0.0001). Centrosomal aberrations correlated to lymphoma grade, mitotic, and proliferation indices, but not to the p53 labeling index. Importantly, diploid MCL contained 31.2% cells with abnormal centrosomes, while tetraploid samples harbored centrosome aberrations in 55.6% of the cells (P<0.0001). These results indicate that centrosome defects are common in NHL and suggest that they may contribute to the acquisition of chromosomal instability typically seen in NHL.

Cell Division↗
PubMed2002

Gangrene of the toes in a patient with chronic myelogenous leukemia after long-term hydroxyurea therapy.

Gangrene of the toes and digits appears to be a rare but very severe complication of long-term hydroxyurea therapy. Nothing is known regarding the pathophysiology and the type of vascular damage leading to this syndrome. Here we report a case of a 49-year-old male presenting with gangrene of the toes of both feet 4.5 years after initiation of hydroxyurea therapy for chronic myelogenous leukemia. Blisters on the toes occurred for the first time 9 months prior to hospitalization. Successively, all ten toes showed signs of beginning gangrene with one toe removed surgically 8 months before admission. Presence of diabetes mellitus or peripheral angiopathy was ruled out and platelet counts were within the physiologic range during the last years, excluding thrombocythemia as another rare cause for gangrene in patients with myeloproliferative diseases. Whereas perimalleolar ulcerations of the legs are a more common complication of hydroxyurea, gangrene of the toes as a consequence of hydroxyurea treatment has been described previously only once in the literature. At this point in time cessation of hydroxyurea treatment appears to be the only therapeutic option, thereby avoiding further progress of gangrene in patients with chronic myelogenous leukemia treated with hydroxyurea.

Antineoplastic Agents↗
PubMed2002

Centrosome replication, genomic instability and cancer.

Karyotypic alterations, including whole chromosome loss or gain, ploidy changes, and a variety of chromosome aberrations are common in cancer cells. If proliferating cells fail to coordinate centrosome duplication with DNA replication, this will inevitably lead to a change in ploidy, and the formation of monopolar or multipolar spindles will generally provoke abnormal segregation of chromosomes. Indeed, it has long been recognized that errors in the centrosome duplication cycle may be an important cause of aneuploidy and thus contribute to cancer formation. This view has recently received fresh impetus with the description of supernumerary centrosomes in almost all solid human tumors. As the primary microtubule organizing center of most eukaryotic cells, the centrosome assures symmetry and bipolarity of the cell division process, a function that is essential for accurate chromosome segregation. In addition, a growing body of evidence indicates that centrosomes might be important for initiating S phase and completing cytokinesis. Centrosomes undergo duplication precisely once before cell division. Recent reports have revealed that this process is linked to the cell division cycle via cyclin-dependent kinase (cdk) 2 activity that couples centriole duplication to the onset of DNA replication at the G(1)/S phase transition. Alterations in G(1)/S phase regulating proteins like the retinoblastoma protein, cyclins D and E, cdk4 and 6, cdk inhibitors p16(INK4A) and p15(INK4B), and p53 are among the most frequent aberrations observed in human malignancies. These alterations might not only lead to unrestrained proliferation, but also cause karyotypic instability by uncontrolled centrosome replication. Since several excellent reports on cell cycle regulation and cancer have been published, this review will focus on the role of centrosomes in cell cycle progression, as well as causes and consequences of aberrant centrosome replication in human neoplasias.

Aneuploidy↗
PubMed2002

Alterations of the cyclin D1/pRb/p16(INK4A) pathway in multiple myeloma.

The retinoblastoma protein (pRb), p16(INK4A), D-type cyclins, and their partners cyclin-dependent kinase (CDK) 4 and 6 constitute a G(1) regulatory pathway commonly targeted in tumorigenesis. Several malignancies show a reciprocal correlation between genetic alterations of single members of the pRb pathway. Therefore, we determined the frequency of Rb deletions and cyclin D1 alterations by fluorescence in situ hybridization as well as 5' CpG island hypermethylation of the p16(INK4A)gene using methylation-specific polymerase chain reaction in bone marrow mononuclear cells from 82 individuals with plasma cell disorders. Alterations in at least one of the components of the pathway were found in 75%. Cyclin D1 translocations or amplifications were detected in 14/82 (17.1%), Rb deletions at 13q14 in 23/82 (28%) of the cases, including three (3.6%) homozygous deletions. p16(INK4A) was hypermethylated in 33/57 (57.9%) of the samples. Further analysis revealed a highly significant correlation between cyclin D1 alterations and extramedullar or leukemic myeloma manifestations (P = 0.014; Fisher's test). Whereas Rb deletions seemed to occur alternatively to cyclin D1 alterations, no reciprocal correlation was found between p16(INK4A) hypermethylations and cyclin D1 or Rb locus aberrations. Cyclin D1 locus alterations and Rb deletions were associated with a significantly worse prognosis whereas p16(INK4A) hypermethylation had no impact on survival. We conclude that cyclin D1 and Rb aberrations seem to occur as alternative events in plasma cell malignancies and contribute to clinical course and prognosis. In contrast, although p16(INK4A) hypermethylation is frequent, inactivation of p16(INK4A) seems not to be involved in the pathogenesis of plasma cell disorders.

Chromosome Aberrations↗
PubMed2001

Structural basis for recognition of the intron branch site RNA by splicing factor 1.

During spliceosome assembly, splicing factor 1 (SF1) specifically recognizes the intron branch point sequence (BPS) UACUAAC in the pre-mRNA transcripts. We show that the KH-QUA2 region of SF1 defines an enlarged KH (hn RNP K) fold which is necessary and sufficient for BPS binding. The 3' part of the BPS (UAAC), including the conserved branch point adenosine (underlined), is specifically recognized in a hydrophobic cleft formed by the Gly-Pro-Arg-Gly motif and the variable loop of the KH domain. The QUA2 region recognizes the 5' nucleotides of the BPS (ACU). The branch point adenosine acting as the nucleophile in the first biochemical step of splicing is deeply buried. BPS RNA recognition suggests how SF1 may facilitate subsequent formation of the prespliceosomal complex A.

Adenosine↗
PubMed2001

Near-threshold photoionization of hydrogenlike uranium studied in ion-atom collisions via the time-reversed process.

Radiative electron capture, the time-reversed photoionization process occurring in ion-atom collisions, provides presently the only access to photoionization studies for very highly charged ions. By applying the deceleration mode of the ESR storage ring, we studied this process in low-energy collisions of bare uranium ions with low- Z target atoms. This technique allows us to extend the current information about photoionization to much lower energies than those accessible for neutral heavy elements in the direct reaction channel. The results prove that for high- Z systems, higher-order multipole contributions and magnetic corrections persist even at energies close to the threshold.

Journal Article↗
PubMed2001

Strong evidence for enhanced multiple electron capture from surfaces in 46 MeV/u Pb81+ collisions with thin carbon foils.

Strong evidence has been found for enhanced multiple electron capture into 46 MeV/u Pb81+ with a significant contribution from the entrance surface of thin carbon foils. Capture of up to five electrons has been observed. The multiple electron capture yield is found to increase with decreasing target thickness for thin targets. A simple model describing the data and showing the importance of capture from surfaces is discussed. Further evidence is found for a pronounced asymmetry between electron capture at the entrance and the exit surfaces. Absolute yields for multiple electron capture and projectile ionization are presented. The experimental total cross sections for single capture and ionization agree well with theory.

Journal Article↗