Diagnostic value of MRI in a pelvic mass of prostatic origin: Part 2.
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Humans↗
Biomedical subjects
Ulrich Vogel
Publications and source records attributed to Ulrich Vogel.
Microarray analyses of meningococcal genome composition and gene regulation: a review of the recent literature.
The development of microarrays for genome comparison and transcriptional profiling along with the public availability of several meningococcal genome sequences has promoted studies elucidating (i) intraspecific and interspecific genomic differences of members of the genus Neisseria, and (ii) the transcriptional response of meningococci to a variety of environmental stresses such as heat shock, iron starvation, serum treatment, and contact with eukaryotic cells. Furthermore, microarray-based finetyping of meningococci is in development. It will remain a difficult, but important, goal to identify sets of genes determining the virulence potential of hypervirulent meningococcal lineages in comparison with apathogenic ones. The recent identification of the meningococcal disease-associated island through the application of microarray analyses has been a step towards this aim. Transcriptional profiling of meningococci has brought about the compilation of large datasets, which also provide information about several regulons. Meningococcal microarray analysis has established a basis for studies clarifying the function of previously unknown genes, and has supported the identification of interesting vaccine candidates. However, harmonization of protocols and tools, as well as central databases are needed to foster the comparability of studies and the integration of knowledge.
Gene Expression Profiling↗
IS1301 fingerprint analysis of Neisseria meningitidis strains belonging to the ET-15 clone.
Meningococci of the ET-15 clone frequently cause clusters of invasive meningococcal disease (IMD) and are associated with a high case-fatality ratio. Timely typing of strains from outbreaks of IMD caused by this clone is hampered by the low variability of its surface antigens. We present a new Southern blot-based typing method for ET-15 meningococci based on the insertion element IS1301, which was present in all 70 ET-15 strains tested. Fingerprints were stable in vitro over a period of 100 days of cultivation on agar plates. The discriminatory power of IS1301 fingerprinting exceeded that of typing by serogrouping and antigen sequencing of the outer membrane proteins PorA and FetA, as determined by the analysis of 52 epidemiologically unrelated strains. In addition, the method provided conclusive results with regard to the comparison of strains from clusters of IMD. The investigation of insertion sites of IS1301 revealed several new intragenic insertions, among others, into open reading frames homologous to mafB and tspB. A previously described insertion in nadA was present in more than two-thirds of the strains analyzed, suggesting that NadA is probably an unreliable vaccine candidate for the prevention of ET-15 disease.
Bacterial Proteins↗
Standardized nonculture techniques recommended for European reference laboratories.
Culture-confirmed diagnosis of meningococcal invasive infections is often hindered by early antibiotic treatment. Nonculture molecular standardized methods are now essential tools for the immediate management of meningococcal infections. The European Monitoring Group on Meningococci (EMGM) recommends the following measures. (1) The implementation of standardized protocols of extraction methods for DNA isolation from clinical specimens for PCR-based identification and genogrouping of Neisseria meningitidis. (2) The use of molecular approaches (sequencing of target genes) for the determination of meningococcal susceptibility to antibiotics, such as sequencing of penA and rpoB genes for susceptibility to penicillin G and rifampicin, respectively. (3) The use of nonculture strain characterization by multilocus sequence typing (MLST) and sequence typing of porA and fetA. These approaches can be implemented either by individual reference laboratories or through collaboration and referral between centres.
Bacterial Outer Membrane Proteins↗
Molecular epidemiology of hospital-acquired vancomycin-resistant enterococci.
Vancomycin-resistant Enterococcus faecium strains are a significant cause of nosocomial infections in predisposed patients. Multiple-locus variable-number tandem repeat analysis (MLVA) has been validated recently by use of a global strain collection. In this report, we applied MLVA together with multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) to type 14 isolates from three clusters of patients colonized or infected with vancomycin-resistant Enterococcus faecium and another 10 epidemiologically unrelated isolates from the same hospital. The clusters could be distinguished by all three typing methods, which proved to be concordant. PFGE patterns provided the highest resolution. We observed seven sequence types (ST), six MLVA types (MT), and nine distinct ST/MT combinations. The combination of MLST and MLVA may be an alternative to PFGE in hospital epidemiology, providing the benefits of high accuracy, reproducibility, and portability.
Bacterial Typing Techniques↗
Evidence for indirect nosocomial transmission of Neisseria meningitidis resulting in two cases of invasive meningococcal disease.
Nosocomial transmission of Neisseria meningitidis has only rarely been reported. Here, we present a significant spatiotemporal association of two cases of invasive meningococcal disease identified by retrospective cluster analysis with the program SaTScan. The most likely epidemiological link was simultaneous hospitalization, resulting in indirect nosocomial transmission.
Adolescent↗
Nuclear trafficking of a gadolinium conjugate in nude mice xenografted with human LN-229 glioma.
We synthesized a novel fluorescein isothiocyanate-labeled gadolinium-diethylenetriamine pentaacetic acid (DTPA) conjugate in which the commonly used gadolinium-DTPA complex is flanked by the nuclear localization sequences of the simian virus-40 T antigen and the acute lymphatic leukemia-1 (ALL-1) protein. The distribution of the conjugate after i.p. or i.v. injection in nude mice bearing human LN-229 glioma xenografts was confirmed by magnetic resonance imaging, with an increase in signal intensity in all the organs and tumors except for healthy brain parenchyma with an intact blood-brain barrier. Nuclear uptake and efflux of the conjugate was demonstrated by confocal laser scanning microscopy. Such gadolinium conjugates may therefore be of value in the development of novel diagnostic and therapeutic agents.
Active Transport, Cell Nucleus↗
Genetic mechanisms for loss of encapsulation in polysialyltransferase-gene-positive meningococci isolated from healthy carriers.
Encapsulated Neisseria meningitidis expressing serogroups A, B, C, W-135, or Y remain a major cause of morbidity and mortality globally. This bacterium is, however, a common commensal inhabitant of the human nasopharynx that causes disease infrequently. Isolates obtained from healthy carriers are frequently unencapsulated and therefore essentially avirulent. The lack of capsule can be due to inactivation of capsule synthesis genes by a variety of genetic mechanisms, or the absence of capsule synthesis genes. Analysis of inactivation mechanisms was undertaken in a diverse but representative set of 166 acapsulate meningococci isolated from carriage that possessed capsule synthesis genes. Slipped strand mispairing in the siaA and siaD genes of the capsule synthesis locus was observed in 39 isolates. Insertion sequence (IS) elements (IS1016-like, IS1106 and IS1301) were responsible for the loss of encapsulation in 46 isolates. Irreversible gene silencing events (insertions, deletions, base exchanges) were found in 47 isolates. Two non-synonymous mutations were identified in close vicinity of the putative active site of the UDP-N-acetylglucosamine 2-epimerase encoded by the siaA gene. The mechanisms for loss of encapsulation were not associated with particular meningococcal genotypes. There was no evidence for successive gene silencing events in the capsule genes, suggesting that the irreversible inactivation events observed were the result of short-term, within-host evolution. These observations are consistent with the postulate that particular meningococcal clonal complexes are associated with possession of a capsule and that this association is important for transmission success.
Adolescent↗
Analysis of the periodontal microbiota in childhood-type hypophosphatasia.
Seven patients with childhood-type hypophosphatasia and healthy control subjects were analysed for microbiological and clinical evidence of periodontitis. The bacterial composition of the subgingival plaque was analysed by 16S rRNA gene cloning and sequencing, DNA-DNA hybridisation with specific probes, and specific PCR. With the exception of the genus Veillonella and the species Eikenella corrodens, no differences between the cohorts in the composition of bacterial orders, families, genera, and species were observed. Accordingly, patients showed only slightly more bleeding on probing (BOP), and slightly higher periodontal probing depth (PPD) values than controls. Although this pilot study did not have the power to assess the prevalence of periodontitis in HP, we suggest that most paediatric patients suffering from HP harbour a subgingival microbiota, which is comparable to that of the healthy population.
Adolescent↗
The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance.
Neisseria meningitidis binds factor H (fH), a key regulator of the alternative complement pathway. A approximately 29 kD fH-binding protein expressed in the meningococcal outer membrane was identified by mass spectrometry as GNA1870, a lipoprotein currently under evaluation as a broad-spectrum meningococcal vaccine candidate. GNA1870 was confirmed as the fH ligand on intact bacteria by 1) abrogation of fH binding upon deleting GNA1870, and 2) blocking fH binding by anti-GNA1870 mAbs. fH bound to whole bacteria and purified rGNA1870 representing each of the three variant GNA1870 families. We showed that the amount of fH binding correlated with the level of bacterial GNA1870 expression. High levels of variant 1 GNA1870 expression (either by allelic replacement of gna1870 or by plasmid-driven high-level expression) in strains that otherwise were low-level GNA1870 expressers (and bound low amounts of fH by flow cytometry) restored high levels of fH binding. Diminished fH binding to the GNA1870 deletion mutants was accompanied by enhanced C3 binding and increased killing of the mutants. Conversely, high levels of GNA1870 expression and fH binding enhanced serum resistance. Our findings support the hypothesis that inhibiting the binding of a complement down-regulator protein to the neisserial surface by specific Ab may enhance intrinsic bactericidal activity of the Ab, resulting in two distinct mechanisms of Ab-mediated vaccine efficacy. These data provide further support for inclusion of this molecule in a meningococcal vaccine. To reflect the critical function of this molecule, we suggest calling it fH-binding protein.
Adjuvants, Immunologic↗
Diagnostic value of MRI in a pelvic mass of prostatic origin.
We report on the case of a 55-year-old male with acute urinary retention, caused by a large pelvic mass. Contrast enhanced computed tomography showed a vascularized prostatic mass with calcifications. To rule out potential bladder and rectum infiltration and to optimize imaging prior to surgical exploration, an MRI examination including MR angiography and spectroscopy was performed. Clinical findings including intraoperative results are presented in this report in detail and correlated to the results of the state of the art magnetic resonance imaging.
Calcinosis↗
Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients.
BACKGROUND: The persistence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with poor prognosis. Preliminary studies indicated that these patients might benefit from secondary adjuvant targeted therapy. HER2 protein is suggested as one of the most promising targets. The aims of this study were (1) to determine the HER2 status of DTC in BM of breast cancer patients and (2) to compare the HER2 status of DTC and corresponding primary tumors. METHODS: BM aspirates from 137 primary breast cancer patients were included into the study. A double staining procedure was used for the identification of cytokeratin-positive (CK)/HER2 positive cells. HER2 status of the primary tumor was immunohistochemically assessed by the HERCEP-test. RESULTS: In 46 of 137 (34%) breast cancer patients CK-positive cells were detectable in BM. DTC with HER2 positivity were found in 20 (43%) of these patients. The HER2 expression on DTC was heterogeneous in 7 of 17 (41%) patients. Concordance rate of HER2 status between primary tumor and DTC was 62%. In 12 of 20 patients with HER2 negative tumors HER2 positive DTC were detected. CONCLUSIONS: HER2 positive DTC can be detected in patients with HER2 negative primary tumors. Therefore, the antigenic profile of DTC may be considered for treatment decision since these patients might actually benefit from trastuzumab. However, the HER2 overexpression on DTC is heterogeneous in individual patients which may reduce the efficacy of an immunotherapy based strategy directed against HER2-antigen only.
Adult↗
Evolution of bacteriophages infecting encapsulated bacteria: lessons from Escherichia coli K1-specific phages.
Bacterial capsules are not only important virulence factors, but also provide attachment sites for bacteriophages that possess capsule degrading enzymes as tailspike proteins. To gain insight into the evolution of these specialized viruses, we studied a panel of tailed phages specific for Escherichia coli K1, a neuroinvasive pathogen with a polysialic acid capsule. Genome sequencing of two lytic K1-phages and comparative analyses including a K1-prophage revealed that K1-phages did not evolve from a common ancestor. By contrast, each phage is related to a different progenitor type, namely T7-, SP6-, and P22-like phages, and gained new host specificity by horizontal uptake of an endosialidase gene. The new tailspikes emerged by combining endosialidase domains with the capsid binding module of the respective ancestor. For SP6-like phages, we identified a degenerated tailspike protein which now acts as versatile adaptor protein interconnecting tail and newly acquired tailspikes and demonstrate that this adapter utilizes an N-terminal undecapeptide interface to bind otherwise unrelated tailspikes. Combining biochemical and sequence analyses with available structural data, we provide new molecular insight into basic mechanisms that allow changes in host specificity while a conserved head and tail architecture is maintained. Thereby, the present study contributes not only to an improved understanding of phage evolution and host-range extension but may also facilitate the on purpose design of therapeutic phages based on well-characterized template phages.
Bacterial Capsules↗
Meningococcal biofilm formation: structure, development and phenotypes in a standardized continuous flow system.
We show that in a standardized in vitro flow system unencapsulated variants of genetically diverse lineages of Neisseria meningitidis formed biofilms, that could be maintained for more than 96 h. Biofilm cells were resistant to penicillin, but not to rifampin or ciprofloxacin. For some strains, microcolony formation within biofilms was observed. Microcolony formation in strain MC58 depended on a functional copy of the pilE gene encoding the pilus subunit pilin, and was associated with twitching of cells. Nevertheless, unpiliated pilE mutants formed biofilms showing that attachment and accumulation of cells did not depend on pilus expression. Mutation and complementation analysis revealed that the type IV pilus-associated protein PilX, which was recently shown to mediate interbacterial aggregation, indirectly supported microcolony formation by contributing to pilus expression. A large number of PilX alleles was identified among genetically diverse meningococcal strains. PilX alleles differed in their propensity to support autoaggregation of cells in suspension, but not in their ability to support microcolony formation within biofilms in the continuous flow system.
Bacterial Capsules↗
Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis.
Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor C4b-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C4bp, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of C4b by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation.
Amino Acid Sequence↗
Cathepsin D expression in renal cell cancer-clinical implications.
BACKGROUND: Whereas the expression of Cathepsin D (Cath D) is suggested to enhance the biological aggressiveness of human malignancies, its role in renal cell carcinoma (RCC), however, has not been investigated. METHODS: By tissue microarray analysis, tumor and benign tissue samples from 176 RCC patients were investigated for Cath D expression by immunohistochemistry and Western blots. Expression levels were correlated to clinical variables and to the postoperative outcome. RESULTS: High Cath D expression levels were detected in 29%/9% of tumor and benign tissue samples, respectively (p < 0.0001). In case of a high vs. low Cath D expression level, development of distant metastases was observed in 12% vs. 88% of cases (p < 0.05). With a median follow-up of 50 (2-146) months, high level Cath D expression was correlated with an improved long-term survival when compared with patients presenting with decreased expression [median long-term survival: 82 vs. 53 months in case of a high vs. low expression level] (p < 0.05). CONCLUSIONS: The Cath D staining pattern predicted a reduced risk for metastatic spread and tumor dependent death, hereby indicating its role as a biological variable revealing additional prognostic information for renal cell cancer patients. Increased expression of Cath D in tumor vs. benign tissue samples might indicate a role for the development and progression of RCC.
Biomarkers, Tumor↗
Genetic analysis of meningococci carried by children and young adults.
BACKGROUND: Neisseria meningitidis is a diverse commensal bacterium that occasionally causes severe invasive disease. The relationship between meningococcal genotype and capsular polysaccharide, the principal virulence factor and vaccine component, was investigated in carried meningococci isolated from 8000 children and young adults in Bavaria, Germany. METHODS: Of the 830 meningococci isolated (carriage rate, 10.4%) by microbiological techniques, 822 were characterized by serogrouping, multilocus sequence typing, and genetic analysis of the capsule region. Statistical and population genetic analyses were applied to these data. RESULTS: The rapid increase in carriage rates with age of carrier, the low prevalence of hyperinvasive meningococci, and the relative prevalence of the 4 disease-associated serogroups were consistent with earlier observations. There was no genetic structuring of the meningococcal population by age of carrier or sampling location; however, there was significant geographic structuring of the meningococci isolated in civil, but not military, institutions. The rate of capsule gene expression did not vary with age of carrier or meningococcal genotype, except for serogroup C, for which increased expression was associated with ST-11 (formerly ET-37) complex meningococci. CONCLUSIONS: Serogroup C capsule expression during carriage may contribute to the invasive character of ST-11 complex meningococci and to the high efficacy of meningococcal serogroup C conjugate polysaccharide vaccine.
Adolescent↗
DNA sequence-based tandem repeat analysis of the clfB gene is less discriminatory than spa typing for methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) are a major challenge for hospital hygiene. Typing by DNA sequence analysis of the repeat region of the protein A gene (spa) significantly improved typing of MRSA in the hospital setting. However, microevolution of spa repeats in epidemic clones appears to occur at a fairly slow clock rate. Therefore, DNA sequence-based methods providing additional resolution are desirable in some situations. We evaluated the use of the clfB repeat region proposed recently by others as a possible complementation to spa typing. Using epidemic MRSA isolates from two German university hospitals, we show that the clfB repeat region does not offer any additional discriminatory power.
Adhesins, Bacterial↗