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Berlin Brandenburg

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  • 1
    Language: English
    In: The Journal of infectious diseases, 15 April 2008, Vol.197(8), pp.1103-9
    Description: Haemophilus ducreyi contains 3 TonB-dependent receptors: the hemoglobin receptor HgbA, which is required for virulence in humans; the heme receptor TdhA; and an uncharacterized conserved hypothetical protein TdX (HD0646). A double tdX/tdhA mutant (FX527) was constructed on the background of a human-passaged variant of strain 35000 (35000HP). Six volunteers were infected with 35000HP at 3 sites on one arm and with FX527 at 3 sites on the other. The pustule formation rate was 55.6% (95% confidence interval [CI], 35.7%-75.4%) at 18 parent-strain sites and 44.4% (95% CI, 15.0%-73.9%) at 18 mutant-strain sites (P = .51). Similar amounts of 35000HP and FX527 were recovered from pustules in semiquantitative culture. Thus, TdX and TdhA are not necessary for virulence, whereas HgbA is both necessary and sufficient for virulence in humans. The data suggest that hemoglobin is the sole source of heme/iron used by H. ducreyi in vivo and has implications for the potential of HgbA as a vaccine.
    Keywords: Bacterial Outer Membrane Proteins -- Biosynthesis ; Bacterial Proteins -- Biosynthesis ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Pathogenicity ; Membrane Proteins -- Biosynthesis
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 2
    Language: English
    In: The Journal of infectious diseases, 01 June 2008, Vol.197(11), pp.1531-6
    Description: Haemophilus ducreyi 35000HP contains a cluster of homologues of genes required for the synthesis of enterobacterial common antigen (ECA), suggesting that H. ducreyi may express a putative ECA-like glycoconjugate. WecA initiates the synthesis of ECA by transferring N-acetylglucosamine to undecaprenyl-P, to form lipid I. A wecA mutant (35000HPwecA) was constructed, and 5 volunteers were inoculated at 3 sites with fixed doses of 35000HP on one arm and at 3 sites with varying doses of 35000HPwecA on the other arm. 35000HPwecA caused pustules to form at 3 sites inoculated with a dose 2.5-fold higher than that of 35000HP. However, at sites inoculated with similar doses of 35000HP and 35000HPwecA, pustules developed at 46.7% (95% confidence interval [CI], 23.3%-70.0%) of 15 parent-strain sites and at 8.3% (95% CI, 0.01%-23.6%) of 12 mutant-strain sites (P = .013). Thus, the expression of wecA contributes to the ability of H. ducreyi to cause pustules in humans.
    Keywords: Multigene Family ; Antigens, Bacterial -- Genetics ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Genetics
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 3
    In: Infection and Immunity, 2007, Vol. 75(12), p.5678
    Description: Dendritic cells (DC) orchestrate innate and adaptive immune responses to bacteria. How Haemophilus ducreyi, which causes genital ulcers and regional lymphadenitis, interacts with DC is unknown. H. ducreyi evades uptake by polymorphonuclear leukocyte and macrophage-like cell lines by secreting LspA1 and LspA2. Many H. ducreyi strains express cytolethal distending toxin (CDT), and recombinant CDT causes apoptosis of DC in vitro. Here, we examined interactions between DC and H. ducreyi 35000HP, which produces LspA1, LspA2, and CDT. In human volunteers infected with 35000HP, the ratio of myeloid DC to plasmacytoid DC was 2.8:1 in lesions, compared to a ratio of 1:1 in peripheral blood. Using myeloid DC derived from monocytes as surrogates for lesional DC, we found that DC infected with 35000HP remained as viable as uninfected DC for up to 48 h. Gentamicin protection and confocal microscopy assays demonstrated that DC ingested and killed 35000HP, but killing was incomplete at 48 h. The expression of LspA1 and LspA2 did not inhibit the uptake of H. ducreyi, despite inactivating Src kinases. Infection of DC with live 35000HP caused less cell surface marker activation than infection with heat-killed 35000HP and lipopolysaccharide (LPS) and inhibited maturation by LPS. However, infection of DC with live bacteria caused the secretion of significantly higher levels of interleukin-6 and tumor necrosis factor alpha than infection with heat-killed bacteria and LPS. The survival of H. ducreyi in DC may provide a mechanism by which the organism traffics to lymph nodes. Partial activation of DC may abrogate the establishment of a full Th1 response and an environment that promotes phagocytosis.
    Keywords: Chancroid -- Immunology ; Dendritic Cells -- Immunology ; Haemophilus Ducreyi -- Immunology ; Myeloid Cells -- Immunology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 4
    Language: English
    In: Psychopharmacology, 2016, Vol.233(4), pp.715-725
    Description: Rationale There is an emerging body of evidence that implicates a crucial role of [gamma]-aminobutyric acid subtype A (GABA.sub.A) receptors in modulating the rewarding effects of a number of abused drugs. Modulation of GABA.sub.A receptors may therefore represent a novel drug-class independent mechanism for the development of abuse treatment pharmacotherapeutics. Objectives We tested the hypothesis that the GABA.sub.A receptor benzodiazepine-site (BDZ) negative modulator Ro15-4513 would reduce the reward-related effects of three pharmacologically dissimilar drugs; toluene vapor, d-methamphetamine, and diazepam using intracranial self-stimulation (ICSS) in mice. We also examined whether Ro15-4513 attenuated dopamine release produced by d-methamphetamine in an in vivo microdialysis procedure. Results Ro15-4513 abolished ICSS reward facilitation produced by all three abused drugs at Ro15-4513 doses which had no effect on ICSS when administered alone. In contrast, the BDZ antagonist flumazenil only attenuated the ICSS-facilitating effects of diazepam. Administration of the same dose of Ro15-4513 which abolished drug-facilitated ICSS produced a 58 % decrease in d-methamphetamine-stimulated dopamine in the nucleus accumbens of mice relative to d-methamphetamine alone. Conclusions These results demonstrate that negative modulation of GABA.sub.A receptors can produce profound reductions in reward-related effects of a diverse group of drugs that activate the mesolimbic reward pathway through different mechanisms. These data suggest that pharmacological modulation of GABA.sub.A receptors may represent a viable pathway for the development of drug abuse pharmacotherapies.
    Keywords: Benzodiazepine ; D-methamphetamine ; Ro15-4513 ; Intracranial self-stimulation (ICSS) ; Toluene ; Inhalant abuse ; GABA ; Brain stimulation reward (BSR) ; Flumazenil ; Negative allosteric modulation
    ISSN: 0033-3158
    E-ISSN: 1432-2072
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  • 5
    Language: English
    In: Biophysical Journal, 01/2010, Vol.98(3), S1, p.174a
    ISSN: 00063495
    E-ISSN: 15420086
    Source: Elsevier (via CrossRef)
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(9), p.e73679
    Description: PURPOSE: Metastatic neuroendocrine tumors secrete serotonin and other vasoactive substances that are responsible for carcinoid syndrome and carcinoid heart disease. We sought to evaluate the discriminatory utility of diagnostic biomarkers in determining the presence and severity of carcinoid heart disease in patients with metastatic neuroendocrine tumors. PATIENTS AND METHODS: A cross-sectional study of patients with neuroendocrine tumors with documented liver metastases and/or carcinoid syndrome between April 2009-October 2012 in 5 tertiary referral centers. Serum was analyzed for Chromogranin A, Chromogranin B and N-terminal pro Brain Natriuretic Peptide (NT-proBNP). Plasma was analyzed for Neurokinin A and 5-Hydroxyindoleacetic acid (5HIAA). Echocardiography was used to determine the presence and severity of carcinoid heart disease. Non-parametric receiver operating characteristic curves were constructed for biomarkers, and the area under the curve determined. The severity of cardiac involvement was correlated with the concentration of each biomarker. RESULTS: A total of 187 patients were identified of whom 37 (20%) had carcinoid heart disease. Significantly higher median values of all biomarkers were found in the patients with cardiac involvement. NT-proBNP and plasma 5HIAA had the highest areas under the curve for the prediction of carcinoid heart disease [NT-proBNP 0.82 (95% confidence interval 0.74-0.90, p〈0.0001) and 5HIAA 0.85 (95% confidence interval 0.78-0.92, p〈0.0001]. NT-proBNP was moderately correlated (r = 0.48, p〈0.001) whereas plasma 5HIAA was only weakly correlated (r = 0.34, p〈0.001) with the echocardiographic severity score. CONCLUSION: NT-proBNP and plasma 5HIAA are both sensitive and specific biomarkers for the presence of carcinoid heart disease whereas only NT-proBNP is moderately correlated with disease severity.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: Journal of cancer education : the official journal of the American Association for Cancer Education, August 2019, Vol.34(4), pp.654-657
    Description: Latina women continue to face disproportionate breast cancer risk and well-documented breast health care barriers in Philadelphia. In response to breast health needs among Latinas in Philadelphia, a health-focused community-based organization, in partnership with a network of social and health service providers, began offering community-based navigation in 2005. Later, through funding from a federal agency, the organization launched the Naveguemos con Salud (NCS) Breast Health Partnership Project from 2010 to 2013. NCS offered breast health awareness and education to a broad audience of Latinas in Philadelphia and community-based navigation services to all interested in accessing a clinical breast exam (CBE) and/or mammogram. A 2017 survey revisited breast health needs among the same core population to inform next steps. Here, we explore how findings and lessons learned from a past program and an assessment of current needs can inform future community-clinical linkage and community-based navigation to improve access to breast cancer screening and a continuum of care for Latinas.
    Keywords: Breast Cancer ; Community-Based ; Latina ; Navigation ; Screening ; Women’s Health
    ISSN: 08858195
    E-ISSN: 1543-0154
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  • 8
    Language: English
    In: Analytical Chemistry, March 15, 2005, Vol.77(6), p.1928(3)
    Description: We report a novel gas-driven high-speed rotating disk electrode (HSRDE). The HSRDE when immersed in an aqueous solution rotates at ~650 Hz, generating laminar flow resulting in a diffusion layer, under steady-state conditions, of thickness ~2 [micro]m. The use of high-pressure gas to drive the rotator offers significant improvement in electrical noise as compared to conventional mechanically driven devices. The electroanalytical utility of the HSRDE was exemplified by the anodic stripping voltammetry of arsenic(III) at a gold working electrode. The charge under the arsenic stripping peak was found to increase by more than 1 order of magnitude under the enhanced mass transport regime at the HSRDE in comparison to that seen under quiescent conditions.
    Keywords: Electrochemistry -- Research ; Electrodes -- Research
    ISSN: 0003-2700
    E-ISSN: 15206882
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  • 9
    Language: English
    In: Intensive Care Medicine, 2009, Vol.35(5), pp.854-861
    Description: Byline: David J. W. Knight (1), Dale Gardiner (2), Amanda Banks (2), Susan E. Snape (3), Vivienne C. Weston (3), Stig Bengmark (4), Keith J. Girling (2,5) Keywords: Probiotics; Enteral nutrition; Nosocomial infections; Intensive care Abstract: Objective To investigate the effect of enteral Synbiotic 2000 FORTE.sup.(r) (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients. Design Prospective, randomised, double blind, placebo controlled trial. Setting Tertiary referral centre, general Adult Intensive Care Unit (ICU). Patients and participants 259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled. Intervention All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE.sup.(r) (twice a day) or a cellulose-based placebo for a maximum of 28 days. Measurements and results Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively. Conclusions Enteral administration of Synbiotic 2000 FORTE.sup.(r) has no statistically significant impact on the incidence of VAP in critically ill patients. Author Affiliation: (1) Department of Intensive Care, Christchurch Hospital, Christchurch, New Zealand (2) Department of Critical Care, Queen's Medical Centre, Nottingham, UK (3) Department of Microbiology, Queen's Medical Centre, Nottingham, UK (4) Department of Surgery, University College London, London, UK (5) Adult Intensive Care Unit, Queen's Medical Centre, Nottingham, NG7 2UH, UK Article History: Registration Date: 28/11/2008 Received Date: 10/12/2007 Accepted Date: 28/10/2008 Online Date: 16/12/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1368-1) contains supplementary material, which is available to authorized users.
    Keywords: Probiotics ; Enteral nutrition ; Nosocomial infections ; Intensive care
    ISSN: 0342-4642
    E-ISSN: 1432-1238
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  • 10
    Language: English
    In: Archives of pathology & laboratory medicine, January 2013, Vol.137(1), pp.32-40
    Description: Precise subtype diagnosis of non-small cell lung carcinoma is increasingly relevant, based on the availability of subtype-specific therapies, such as bevacizumab and pemetrexed, and based on the subtype-specific prevalence of activating epidermal growth factor receptor mutations. To establish a baseline measure of interobserver reproducibility for non-small cell lung carcinoma diagnoses with hematoxylin-eosin for the current 2004 World Health Organization classification, to estimate interobserver reproducibility for the therapeutically relevant squamous/nonsquamous subsets, and to examine characteristics that improve interobserver reproducibility. Primary, resected lung cancer specimens were converted to digital (virtual) slides. Based on a single hematoxylin-eosin virtual slide, pathologists were asked to assign a diagnosis using the 2004 World Health Organization classification. Kappa statistics were calculated for each pathologist-pair for each slide and were summarized by classification scheme, pulmonary pathology expertise, diagnostic confidence, and neoplastic grade. The 12 pulmonary pathology experts and the 12 community pathologists each independently diagnosed 48 to 96 single hematoxylin-eosin digital slides derived from 96 cases of non-small cell lung carcinoma resection. Overall agreement improved with simplification from the comprehensive 44 World Health Organization diagnoses (κ  =  0.25) to their 10 major header subtypes (κ  =  0.48) and improved again with simplification into the therapeutically relevant squamous/nonsquamous dichotomy (κ  =  0.55). Multivariate analysis showed that higher diagnostic agreement was associated with better differentiation, better slide quality, higher diagnostic confidence, similar years of pathology experience, and pulmonary pathology expertise. These data define the baseline diagnostic agreement for hematoxylin-eosin diagnosis of non-small cell lung carcinoma, allowing future studies to test for improved diagnostic agreement with reflex ancillary tests.
    Keywords: Carcinoma, Non-Small-Cell Lung -- Classification ; Lung Neoplasms -- Classification
    E-ISSN: 1543-2165
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