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  • MEDLINE/PubMed (NLM)  (24)
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  • 1
    Language: English
    In: BMC microbiology, 24 June 2014, Vol.14, pp.166
    Description: Bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. Such lipoproteins are viable vaccine candidates. Haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. One such lipoprotein, OmpP4, is homologous to the outer membrane lipoprotein e (P4) of H. influenzae. In H. influenzae, e (P4) stimulates production of bactericidal and protective antibodies and contributes to pathogenesis by facilitating acquisition of the essential nutrients heme and nicotinamide adenine dinucleotide (NAD). Here, we tested the hypothesis that, like its homolog, H. ducreyi OmpP4 contributes to virulence and stimulates production of bactericidal antibodies. We determined that OmpP4 is broadly conserved among clinical isolates of H. ducreyi. We next constructed and characterized an isogenic ompP4 mutant, designated 35000HPompP4, in H. ducreyi strain 35000HP. To test whether OmpP4 was necessary for virulence in humans, eight healthy adults were experimentally infected. Each subject was inoculated with a fixed dose of 35000HP on one arm and three doses of 35000HPompP4 on the other arm. The overall parent and mutant pustule formation rates were 52.4% and 47.6%, respectively (P = 0.74). These results indicate that expression of OmpP4 in not necessary for H. ducreyi to initiate disease or progress to pustule formation in humans. Hyperimmune mouse serum raised against purified, recombinant OmpP4 did not promote bactericidal killing of 35000HP or phagocytosis by J774A.1 mouse macrophages in serum bactericidal and phagocytosis assays, respectively. Our data suggest that, unlike e (P4), H. ducreyi OmpP4 is not a suitable vaccine candidate. OmpP4 may be dispensable for virulence because of redundant mechanisms in H. ducreyi for heme acquisition and NAD utilization.
    Keywords: Bacterial Outer Membrane Proteins -- Metabolism ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Pathogenicity ; Virulence Factors -- Metabolism
    E-ISSN: 1471-2180
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  • 2
    Language: English
    In: The Journal of infectious diseases, November 2012, Vol.206(9), pp.1407-14
    Description: Haemophilus ducreyi encounters several classes of antimicrobial peptides (APs) in vivo and utilizes the sensitive-to-antimicrobial-peptides (Sap) transporter as one mechanism of AP resistance. A mutant lacking the periplasmic solute-binding component, SapA, was somewhat more sensitive to the cathelicidin LL-37 than the parent strain and was partially attenuated for virulence. The partial attenuation led us to question whether the transporter is fully abrogated in the sapA mutant. We generated a nonpolar sapBC mutant, which lacks both inner membrane permeases of the Sap transporter, and tested the mutant for virulence in human volunteers. In vitro, we compared LL-37 resistance phenotypes of the sapBC and sapA mutants. Unlike the sapA mutant, the sapBC mutant was fully attenuated for virulence in human volunteers. In vitro, the sapBC mutant exhibited significantly greater sensitivity than the sapA mutant to killing by LL-37. Similar to the sapA mutant, the sapBC mutant did not affect H. ducreyi's resistance to human defensins. Compared with the sapA mutant, the sapBC mutant exhibited greater attenuation in vivo, which directly correlated with increased sensitivity to LL-37 in vitro. These results strongly suggest that the SapBC channel retains activity when SapA is removed.
    Keywords: Drug Resistance, Bacterial ; Antimicrobial Cationic Peptides -- Pharmacology ; Haemophilus Ducreyi -- Enzymology ; Membrane Transport Proteins -- Metabolism ; Virulence Factors -- Metabolism
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 3
    Language: English
    In: The Journal of infectious diseases, 01 March 2009, Vol.199(5), pp.684-92
    Description: A gene expression study of Haemophilus ducreyi identified the hypothetical lipoprotein HD0192, renamed here "fibrinogen binder A" (FgbA), as being preferentially expressed in vivo. To test the role played by fgbA in virulence, an isogenic fgbA mutant (35000HPfgbA) was constructed using H. ducreyi 35000HP, and 6 volunteers were experimentally infected with 35000HP or 35000HPfgbA. The overall pustule-formation rate was 61.1% at parent sites and 22.2% at mutant sites (P = .019). Papules were significantly smaller at mutant sites than at parent sites (13.3 vs. 37.9 mm(2); P = .002) 24 h after inoculation. Thus, fgbA contributed significantly to the virulence of H. ducreyi in humans. In vitro experiments demonstrated that fgbA encodes a fibrinogen-binding protein; no other fibrinogen-binding proteins were identified in 35000HP. fgbA was conserved among clinical isolates of both class I and II H. ducreyi strains, supporting the finding that fgbA is important for H. ducreyi infection.
    Keywords: Bacterial Proteins -- Metabolism ; Chancroid -- Microbiology ; Fibrinogen -- Metabolism ; Haemophilus Ducreyi -- Genetics ; Lipoproteins -- Metabolism
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 4
    In: Infection and Immunity, 2001, Vol. 69(4), p.2549
    Description: In a previous study, Haemophilus ducreyi was found in the pustule and dermis of samples obtained at the clinical end point in the human model of infection. To understand the kinetics of localization, we examined infected sites at 0, 24, and 48 h after inoculation and at the clinical end point. Immediately after inoculation, bacteria were found predominantly in the dermis but also in the epidermis. Few bacteria were detectable at 24 h; however, by 48 h, bacteria were readily seen in the pustule and dermis. H. ducreyi was associated with polymorphonuclear leukocytes and macrophages in the pustule and at its base, but was not associated with T cells, Langerhans' cells, or fibroblasts. H. ducreyi colocalized with collagen and fibrin but not laminin or fibronectin. Association with phagocytes, collagen, and fibrin was seen as early as 48 h and persisted at the pustular stage of disease. Optical sectioning by confocal microscopy and transmission electron microscopy both failed to demonstrate intracellular H. ducreyi. These data identify collagen and fibrin as potentially important targets of adherence in vivo and strongly suggest that H. ducreyi remains extracellular throughout infection and survives by resisting phagocytic killing in vivo.
    Keywords: Bacterial Adhesion ; Collagen -- Physiology ; Fibrin -- Physiology ; Haemophilus Ducreyi -- Physiology ; Phagocytes -- Microbiology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 5
    Language: English
    In: Health Psychology, 2016, Vol.35(6), pp.584-593
    Description: Objective: Coping processes directed toward avoiding and approaching stressor-related thoughts and emotions predict psychological adjustment. However, few studies have examined how the relationship between dispositional emotional tendencies and stressor-specific coping affects outcomes. The aim of the current study was to examine the association of dispositional emotional expressivity (i.e., the propensity to experience and express emotions strongly) with cancer-specific coping through avoidance and emotional approach to predict intrusive thoughts and depressive symptoms in Latinas with breast cancer. Method: Recently diagnosed Latina breast cancer patients receiving treatment completed standardized assessments via interview at 2 time points: within 18 months of diagnosis (Time 1; N = 95) and 3 months later (Time 2; N = 79). Results: Most women were immigrants (93%), reported a combined household income of $20,000 or less (75%), did not graduate from high school (59%), and primarily spoke Spanish (88%). In path analyses, more recent immigration was associated with greater dispositional expressivity, which in turn was associated with coping with the cancer experience using both greater avoidance and emotional approach strategies. Only avoidance-oriented strategies predicted an increase in intrusive thoughts at 3 months. No significant effects on depressive symptoms were observed. Conclusions: Findings suggest that Latina breast cancer patients who have a propensity to experience and express emotions strongly may be initially overwhelmed by their cancer-related emotions and consequently turn to avoidance-oriented and emotional approach strategies to cope with their diagnosis. Avoidance-oriented coping in turn may uniquely predict an increase in cancer-related intrusive thoughts 3 months later.
    Keywords: Avoidance ; Approach ; Breast Cancer ; Coping ; Latina
    ISSN: 0278-6133
    E-ISSN: 1930-7810
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  • 6
    Language: English
    In: Journal of Behavioral Medicine, 2017, Vol.40(6), pp.875-885
    Description: Breast cancer patients often experience adverse physical side effects of medical treatments. According to the biobehavioral model of cancer stress and disease, life stress during diagnosis and treatment may negatively influence the trajectory of women’s physical health-related adjustment to breast cancer. This longitudinal study examined chronic and episodic stress as predictors of bothersome physical symptoms during the year after breast cancer diagnosis. Women diagnosed with breast cancer in the previous 4 months ( N  = 460) completed a life stress interview for contextual assessment of chronic and episodic stress severity at study entry and 9 months later. Physical symptom bother (e.g., pain, fatigue) was measured at study entry, every 6 weeks through 6 months, and at nine and 12 months. In multilevel structural equation modeling (MSEM) analyses, both chronic stress and episodic stress occurring shortly after diagnosis predicted greater physical symptom bother over the study period. Episodic stress reported to have occurred prior to diagnosis did not predict symptom bother in MSEM analyses, and the interaction between chronic and episodic stress on symptom bother was not significant. Results suggest that ongoing chronic stress and episodic stress occurring shortly after breast cancer diagnosis are important predictors of bothersome symptoms during and after cancer treatment. Screening for chronic stress and recent stressful life events in the months following diagnosis may help to identify breast cancer patients at risk for persistent and bothersome physical symptoms. Interventions to prevent or ameliorate treatment-related physical symptoms may confer added benefit by addressing ongoing non-cancer-related stress in women’s lives.
    Keywords: Stress ; Life events ; Breast cancer ; Physical symptoms ; Survivorship
    ISSN: 0160-7715
    E-ISSN: 1573-3521
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  • 7
    Language: English
    In: Annals of Behavioral Medicine, 2016, Vol.50(3), pp.370-384
    Description: BACKGROUND: Few studies examine whether dispositional approach and avoidance coping and stressor-specific coping strategies differentially predict physical adjustment to cancer-related stress.PURPOSE: This study examines dispositional and situational avoidance and approach coping as unique predictors of the bother women experience from physical symptoms after breast cancer treatment, as well as whether situational coping mediates the prediction of bother from physical symptoms by dispositional coping.METHOD: Breast cancer patients (N = 460) diagnosed within the past 3months completed self-report measures of dispositional coping at study entry and of situational coping and bother from physical symptoms every 6weeks through 6months.RESULTS: In multilevel structural equation modeling analyses, both dispositional and situational avoidance predict greater symptom bother. Dispositional, but not situational, approach predicts less symptom bother. Supporting mediation models, dispositional avoidance predicts more symptom bother indirectly through greater situational avoidance. Dispositional approach predicts less symptom bother through less situational avoidance.CONCLUSION: Psychosocial interventions to reduce cancer-related avoidance coping are warranted for cancer survivors who are high in dispositional avoidance and/or low in dispositional approach.
    Keywords: Avoidance ; Approach ; Coping ; Breast cancer ; Physical symptoms
    ISSN: 0883-6612
    E-ISSN: 1532-4796
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  • 8
    In: Infection and Immunity, 2000, Vol. 68(11), p.6441
    Description: Haemophilus ducreyi expresses a peptidoglycan-associated lipoprotein (PAL) that exhibits extensive homology to Haemophilus influenzae protein 6. We constructed an isogenic PAL mutant (35000HP-SMS4) by the use of a suicide vector that contains lacZ as a counterselectable marker. H. ducreyi 35000HP-SMS4 and its parent, 35000HP, had similar growth rates in broth and similar lipooligosaccharide profiles. 35000HP-SMS4 formed smaller, more transparent colonies than 35000HP and, unlike its parent, was hypersensitive to antibiotics. Complementation of the mutant in trans restored the parental phenotypes. To test whether expression of PAL is required for virulence, nine human volunteers were experimentally infected. Each subject was inoculated with two doses (41 to 89 CFU) of live 35000HP and one dose of heat-killed bacteria on one arm and with three doses (ranging from 28 to 800 CFU) of live 35000HP-SMS4 on the other arm. Papules developed at similar rates at sites inoculated with the mutant or parent but were significantly smaller at mutant-inoculated sites than at parent-inoculated sites. The pustule formation rate was 72% (95% confidence interval [CI], 46.5 to 90.3%) at 18 parent sites and 11% (95% CI, 2.4 to 29.2%) at 27 mutant sites (P 〈 0.0001). The rates of recovery of H. ducreyi from surface cultures were 8% (n = 130; 95% CI, 4.3 to 14.6%) for parent-inoculated sites and 0% (n = 120; 95% CI, 0.0 to 2.5%) for mutant-inoculated sites (P 〈 0.001). H. ducreyi was recovered from six of seven biopsied parent-inoculated sites and from one of three biopsied mutant-inoculated sites. Confocal microscopy confirmed that the bacteria present in a mutant inoculation site pustule lacked a PAL-specific epitope. Although biosafety regulations precluded our testing the complemented mutant in humans, these results suggest that expression of PAL facilitates the ability of H. ducreyi to progress to the pustular stage of disease.
    Keywords: Bacterial Outer Membrane Proteins ; Proteoglycans ; Haemophilus Infections -- Etiology ; Haemophilus Ducreyi -- Pathogenicity ; Lipoproteins -- Metabolism ; Peptidoglycan -- Metabolism;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 9
    In: Infection and Immunity, 2003, Vol. 71(11), p.6658
    Description: With human volunteers inoculated at two sites with Haemophilus ducreyi, outcomes for a subject were not independent. In a reinfection trial, 2 of 11 previous pustule formers and 6 of 10 previous resolvers resolved all sites of infection. There was no correlation between serum bactericidal or phagocytic activity and outcome in the trial. These data indicate that different hosts are differentially susceptible to disease progression versus resolution in the model.
    Keywords: Haemophilus Ducreyi ; Infection ; Host-Pathogen Interactions ; Pathogenesis ; Models ; Microflora ; Case Reports ; Case Reports;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 10
    In: British Journal of Health Psychology, September 2017, Vol.22(3), pp.609-626
    Description: Byline: Margaret R. Bauer, Joshua F. Wiley, Karen L. Weihs, Annette L. Stanton Keywords: avoidance; intrusive thoughts; coping; cognitive processing; cancer Objectives Theories and research regarding cognitive and emotional processing during the experience of profound stressors suggest that the presence of intrusive thoughts and feelings predicts greater use of avoidance and that the use of avoidance paradoxically predicts more intrusions. However, empirical investigations of their purported bidirectional relationship are limited. Design This study presents a longitudinal investigation of the reciprocal relationship between intrusions and avoidance coping over a 6-month period in the year following breast cancer diagnosis. Methods Breast cancer patients (N = 460) completed measures of cancer-related intrusions and avoidance at study entry, 3 months, and 6 months later (i.e., an average of 2, 5, and 8 months after diagnosis, respectively). Results Cross-lagged panel analyses revealed that intrusive thoughts, feelings, and images at study entry predicted greater avoidance 3 months later, and avoidance coping at study entry predicted intrusions 3 months later, controlling for the stability of intrusions and avoidance as well as time since diagnosis. Findings were not statistically significant for avoidance predicting intrusions, or vice versa, between the 3-month and the 6-month assessment period, during which they declined. Conclusions These findings provide empirical support for the theoretical contention that avoidance and intrusive thoughts and emotions reciprocally influence one another following stressful events. Additionally, in the months shortly after breast cancer diagnosis, intrusions and avoidance are positively related. However, the relationships attenuate over time, which could indicate resolved cognitive and emotional processing of the cancer experience. Statement of contribution What is already known on this subject? Following stressful life events, individuals often experience intrusive thoughts and feelings related to the event and they report avoidance of such reminders. Many studies demonstrate that greater intrusions predict more subsequent use of avoidance coping, and other studies show that greater use of avoidance predicts more intrusions. Their reciprocal relation has not been examined, however. What does this study add? This is the first examination of the concurrent, reciprocal influence of intrusions and avoidance. Findings suggest that accounting for the bidirectional influence of avoidance and intrusions best estimates hypothesized models. Higher intrusions and avoidance predicted each other for the first 3 months after study entry, but the relationship diminished 6 months after study entry, perhaps due to productive mental processing of the stress of breast cancer diagnosis and treatment.
    Keywords: Avoidance ; Intrusive Thoughts ; Coping ; Cognitive Processing ; Cancer
    ISSN: 1359-107X
    E-ISSN: 2044-8287
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