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  • 1
    Keywords: SPECTRA ; CANCER ; Germany ; human ; SUPPORT ; COHORT ; GENOME ; PATIENT ; DNA ; INFECTION ; SKIN ; PCR ; HPV ; BETA ; PREVALENCE ; immunosuppression ; SKIN-CANCER ; papillomaviruses ; GAMMA ; RECIPIENTS ; VIRAL LOAD ; allergy ; cutaneous HPV ; HUMAN PAPILLOMAVIRUSES ; HPV types ; 33 ; ALLERGIES ; organ transplant recipients ; RANGE ; cutaneous warts
    Abstract: BACKGROUND: A broad spectrum of human papillomaviruses (HPV) has been detected in warts from immunocompetent patients and a much more diverse range from immunosuppressed organ transplant recipients (OTR). OBJECTIVES: To determine the HPV types in warts from OTR, we assessed present infections of mucosal (alpha-PV), wart-associated (alpha-, micro- and nu-PV) and cutaneous HPV types (beta-/gamma-PV) in immunocompetent patients and OTR. Patients/methods Forty-one warts from 29 immunocompetent patients (non-OTR) and 53 warts from 33 OTR were analysed for DNA of human alpha-, beta-, gamma-, micro- and nu-PV. For frequent types viral load was determined by quantitative real-time PCR. RESULTS: Compared with non-OTR prevalence of cutaneous HPV (79% vs. 49%, P 〈 0.01) and the number of multiple infections (62% vs. 17%, P 〈 0.0001) were significantly increased. The mean viral load of the wart-associated HPV was more than 10(5)-fold higher compared with human beta-PV in both cohorts. CONCLUSIONS: The high load of wart-associated HPV suggests an active role of these viruses rather than cutaneous types in warts independent of immunosuppression; however, the substantial fraction of warts with low HPV genome copies remains to be explained.
    Type of Publication: Journal article published
    PubMed ID: 19519829
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  • 2
    Keywords: OPTIMIZATION ; PEPTIDE ; INHIBITOR ; tumor ; CELL ; INHIBITION ; KINASE ; MICROSCOPY ; MODEL ; MODELS ; SUPPORT ; SYSTEM ; SYSTEMS ; TOOL ; TUMORS ; ACTIVATION ; cell signaling ; DOMAIN ; BIOLOGY ; CYCLE ; ASSAY ; DESIGN ; PARAMETERS ; RECRUITMENT ; STRATEGIES ; lipids ; UNCERTAINTY ; parameter estimation ; systems biology ; BEHAVIOR ; AFFINITY ; AKT ; REPRESENTATION ; signaling ; PROTOCOL ; FLUORESCENCE MICROSCOPY ; PROFILES ; USA ; COMPOUND ; KINASE INHIBITOR ; lipid ; CALIFORNIA ; STATE ; STRATEGY ; A KINASE ; EXPERIMENTAL-DESIGN ; RANGE ; PI3K ; chemically induced
    Abstract: Differential equation models that describe the dynamic changes of biochemical signaling states are important tools to understand cellular behavior. An essential task in building such representations is to infer the affinities, rate constants, and other parameters of a model from actual measurement data. However, intuitive measurement protocols often fail to generate data that restrict the range of possible parameter values. Here we utilized a numerical method to iteratively design optimal live-cell fluorescence microscopy experiments in order to reveal pharmacological and kinetic parameters of a phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) second messenger signaling process that is deregulated in many tumors. The experimental approach included the activation of endogenous phosphoinositide 3-kinase (PI3K) by chemically induced recruitment of a regulatory peptide, reversible inhibition of PI3K using a kinase inhibitor, and monitoring of the PI3K-mediated production of PIP(3) lipids using the pleckstrin homology (PH) domain of Akt. We found that an intuitively planned and established experimental protocol did not yield data from which relevant parameters could be inferred. Starting from a set of poorly defined model parameters derived from the intuitively planned experiment, we calculated concentration-time profiles for both the inducing and the inhibitory compound that would minimize the predicted uncertainty of parameter estimates. Two cycles of optimization and experimentation were sufficient to narrowly confine the model parameters, with the mean variance of estimates dropping more than sixty-fold. Thus, optimal experimental design proved to be a powerful strategy to minimize the number of experiments needed to infer biological parameters from a cell signaling assay.
    Type of Publication: Journal article published
    PubMed ID: 19911077
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC); 20070426-20070429; Leipzig; DOCSA.06.02 /20070411/
    Publication Date: 2007-04-04
    Keywords: ultrasound ; registration ; aneurysm ; Ultraschall ; Neuronavigation ; Aneurysma ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC); 20070426-20070429; Leipzig; DOCP 026 /20070411/
    Publication Date: 2007-04-04
    Keywords: image registration ; free form deformation ; aneurysm ; Registrierung ; freie Deformation ; Aneurysma ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC); 20070426-20070429; Leipzig; DOCSA.06.01 /20070411/
    Publication Date: 2007-04-04
    Keywords: aneurysm ; imaging ; coregistration ; Aneurysma ; Bildgebung ; Koregistrierung ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
    ISSN: 1617-4623
    Keywords: Key words Gonococci ; aniA ; Pan1 ; Nitrite reductase ; Anaerobiosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The aniA gene of Neisseria gonorrhoeae encodes an outer membrane lipoprotein which is strongly induced when gonococci are grown anaerobically in vitro in the presence of nitrite. Database searches with the amino acid sequence derived from the aniA structural gene revealed significant homologies to copper-containing nitrite reductases from several denitrifying bacteria. We constructed an insertional mutation in the aniA locus of strain MS11 by allelic replacement, to determine whether this locus was necessary for growth in oxygen-depleted environments, and to demonstrate that AniA was indeed a nitrite reductase. The mutant was severely impaired in its ability to grow microaerophilically in the presence of nitrite, and we observed a loss in viability over several hours of incubation. No measurable nitrite reductase activity was detected in the aniA mutant strain, and activity in the strain with a wild-type locus was inducible. Finally, we report investigations to determine whether AniA protein is involved in gonococcal pathogenesis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1617-4623
    Keywords: Key words Gonococci ; Pilli ; Transcription ; Anaerobiosis ; Growth phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The type-4 pilus of Neisseria gonorrhoeae is a dominant surface antigen which facilitates adhesion to host target cells, an essential event in gonococcal infection. pilC2 encodes a 110-kDa protein involved in pilus assembly, pilus-mediated adherence to human epithelial cells in culture and natural competence for DNA transformation. Luciferase activity directed from a chromosomal pilC2::luxAB transcriptional fusion was reduced approximately 4-fold when cells were grown anaerobically. We observed a concomitant reduction in gonococcal piliation by electron microscopy and a reduction in the ability to adhere to ME-180 human epithelial cells when bacteria were grown in the absence of oxygen. Furthermore, we present evidence for growth-phase regulation of the gonococcal pilC2 gene in Escherichia coli, and show that all sequences necessary for growth-phase regulation are contained on a 121-bp pilC2 fragment. Expression from the minimal pilC2 fragment fused to lacZ in single-copy in E. coli was induced 2-fold when cells entered stationary phase. Surprisingly, induction does not require rpoS, the gene, which encodes the starvation-induced sigma factor RpoS. In summary, we have demonstrated that pilC2 is both positively and negatively regulated at the level of transcription. This regulation is most probably relevant to physiological conditions within the human host which influence gonococcal infections.
    Type of Medium: Electronic Resource
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