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  1. Article ; Online: Complement interactions with the pathogenic Neisseriae: clinical features, deficiency states, and evasion mechanisms.

    Lewis, Lisa A / Ram, Sanjay

    FEBS letters

    2020  Volume 594, Issue 16, Page(s) 2670–2694

    Abstract: Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, while Neisseria meningitidis is an important cause of bacterial meningitis and sepsis. Complement is a central arm of innate immune defenses and plays an important role in ... ...

    Abstract Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, while Neisseria meningitidis is an important cause of bacterial meningitis and sepsis. Complement is a central arm of innate immune defenses and plays an important role in combating Neisserial infections. Persons with congenital and acquired defects in complement are at a significantly higher risk for invasive Neisserial infections such as invasive meningococcal disease and disseminated gonococcal infection compared to the general population. Of note, Neisseria gonorrhoeae and Neisseria meningitidis can only infect humans, which in part may be related to their ability to evade only human complement. This review summarizes the epidemiologic and clinical aspects of Neisserial infections in persons with defects in the complement system. Mechanisms used by these pathogens to subvert killing by complement and preclinical studies showing how these complement evasion strategies may be used to counteract the global threat of meningococcal and gonococcal infections are discussed.
    MeSH term(s) Animals ; Complement System Proteins/immunology ; Gonorrhea/immunology ; Gonorrhea/pathology ; Humans ; Immune Evasion ; Meningococcal Infections/immunology ; Meningococcal Infections/pathology ; Neisseria gonorrhoeae/immunology ; Neisseria gonorrhoeae/pathogenicity ; Neisseria meningitidis/immunology ; Neisseria meningitidis/pathogenicity
    Chemical Substances Complement System Proteins (9007-36-7)
    Language English
    Publishing date 2020-03-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.13760
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Alternative pathway amplification and infections

    Shaughnessy, Jutamas / Chabeda, Aleyo / Lewis, Lisa A. / Ram, Sanjay

    Immunological Reviews. 2023 Jan., v. 313, no. 1, p. 162-180

    2023  , Page(s) 162–180

    Abstract: The alternative pathway (AP) is the phylogenetically oldest arm of the complement system and may have evolved to mark pathogens for elimination by phagocytes. Studies using purified AP proteins or AP‐specific serum showed that C3b amplification on ... ...

    Abstract The alternative pathway (AP) is the phylogenetically oldest arm of the complement system and may have evolved to mark pathogens for elimination by phagocytes. Studies using purified AP proteins or AP‐specific serum showed that C3b amplification on bacteria commenced following a lag phase of about 5 min and was highly dependent on the concentration of complement. Most pathogens have evolved several elegant mechanisms to evade complement, including expressing proteases that degrade AP proteins and secreting proteins that block function of C3 convertases. In an example of convergent evolution, many microbes recruit the AP inhibitor factor H (FH) using molecular mechanisms that mimic FH interactions with host cells. In most instances, the AP serves to amplify C3b deposited on microbes by the classical pathway (CP). The role of properdin on microbes appears to be restricted to stabilization of C3 convertases; scant evidence exists for its role as an initiator of the AP on pathogens in the context of serum. Therapeutic complement inhibition carries with it an increased risk of infection. Antibody (Ab)‐dependent AP activation may be critical for complement activation by vaccine‐elicited Ab when the CP is blocked, and its molecular mechanism is discussed.
    Keywords antibodies ; blood serum ; complement ; convergent evolution ; phylogeny ; proteinases ; risk ; therapeutics
    Language English
    Dates of publication 2023-01
    Size p. 162-180
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note REVIEW
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13160
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  3. Article: Complement interactions with the pathogenic Neisseriae: clinical features, deficiency states, and evasion mechanisms

    Lewis, Lisa A. / Ram, Sanjay

    FEBS letters. 2020 Aug., v. 594, no. 16

    2020  

    Abstract: Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, while Neisseria meningitidis is an important cause of bacterial meningitis and sepsis. Complement is a central arm of innate immune defenses and plays an important role in ... ...

    Abstract Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, while Neisseria meningitidis is an important cause of bacterial meningitis and sepsis. Complement is a central arm of innate immune defenses and plays an important role in combating Neisserial infections. Persons with congenital and acquired defects in complement are at a significantly higher risk for invasive Neisserial infections such as invasive meningococcal disease and disseminated gonococcal infection compared to the general population. Of note, Neisseria gonorrhoeae and Neisseria meningitidis can only infect humans, which in part may be related to their ability to evade only human complement. This review summarizes the epidemiologic and clinical aspects of Neisserial infections in persons with defects in the complement system. Mechanisms used by these pathogens to subvert killing by complement and preclinical studies showing how these complement evasion strategies may be used to counteract the global threat of meningococcal and gonococcal infections are discussed.
    Keywords Neisseria gonorrhoeae ; Neisseria meningitidis ; complement ; humans ; meningitis ; risk ; sexually transmitted diseases
    Language English
    Dates of publication 2020-08
    Size p. 2670-2694.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note REVIEW
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.13760
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  4. Article ; Online: Mechanisms by which Factor H protects

    Menon, Smrithi S / Ramirez-Toloza, Galia / Wycoff, Keith L / Ehinger, Sean / Shaughnessy, Jutamas / Ram, Sanjay / Ferreira, Viviana P

    Frontiers in immunology

    2024  Volume 15, Page(s) 1152000

    Abstract: Chagas disease, a chronic disabling disease caused by the ... ...

    Abstract Chagas disease, a chronic disabling disease caused by the protozoan
    MeSH term(s) Humans ; Complement Factor H ; Trypanosoma cruzi ; Chagas Disease/prevention & control
    Chemical Substances Complement Factor H (80295-65-4)
    Language English
    Publishing date 2024-02-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1152000
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The "Black Fungus" in India: The Emerging Syndemic of COVID-19-Associated Mucormycosis.

    Gandra, Sumanth / Ram, Sanjay / Levitz, Stuart M

    Annals of internal medicine

    2021  Volume 174, Issue 9, Page(s) 1301–1302

    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/prevention & control ; Comorbidity ; Dexamethasone/therapeutic use ; Diabetes Complications/immunology ; Glucocorticoids/therapeutic use ; Humans ; Immunocompromised Host ; India/epidemiology ; Mucormycosis/drug therapy ; Mucormycosis/epidemiology ; Mucormycosis/prevention & control ; Prescription Drug Overuse ; Risk Factors ; SARS-CoV-2 ; Syndemic
    Chemical Substances Anti-Bacterial Agents ; Glucocorticoids ; Dexamethasone (7S5I7G3JQL)
    Language English
    Publishing date 2021-06-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 336-0
    ISSN 1539-3704 ; 0003-4819
    ISSN (online) 1539-3704
    ISSN 0003-4819
    DOI 10.7326/M21-2354
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.178/2: Show issues Location:
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  6. Article ; Online: Alternative pathway amplification and infections.

    Shaughnessy, Jutamas / Chabeda, Aleyo / Lewis, Lisa A / Ram, Sanjay

    Immunological reviews

    2022  Volume 313, Issue 1, Page(s) 162–180

    Abstract: The alternative pathway (AP) is the phylogenetically oldest arm of the complement system and may have evolved to mark pathogens for elimination by phagocytes. Studies using purified AP proteins or AP-specific serum showed that C3b amplification on ... ...

    Abstract The alternative pathway (AP) is the phylogenetically oldest arm of the complement system and may have evolved to mark pathogens for elimination by phagocytes. Studies using purified AP proteins or AP-specific serum showed that C3b amplification on bacteria commenced following a lag phase of about 5 min and was highly dependent on the concentration of complement. Most pathogens have evolved several elegant mechanisms to evade complement, including expressing proteases that degrade AP proteins and secreting proteins that block function of C3 convertases. In an example of convergent evolution, many microbes recruit the AP inhibitor factor H (FH) using molecular mechanisms that mimic FH interactions with host cells. In most instances, the AP serves to amplify C3b deposited on microbes by the classical pathway (CP). The role of properdin on microbes appears to be restricted to stabilization of C3 convertases; scant evidence exists for its role as an initiator of the AP on pathogens in the context of serum. Therapeutic complement inhibition carries with it an increased risk of infection. Antibody (Ab)-dependent AP activation may be critical for complement activation by vaccine-elicited Ab when the CP is blocked, and its molecular mechanism is discussed.
    MeSH term(s) Humans ; Complement Activation/physiology ; Complement Pathway, Alternative ; Properdin/metabolism ; Bacterial Infections/metabolism ; Complement C3b/metabolism
    Chemical Substances Properdin (11016-39-0) ; Complement C3b (80295-43-8)
    Language English
    Publishing date 2022-11-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Se 160: Show issues Location:
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  7. Article ; Online: Gardnerella Vaginolysin Potentiates Glycan Molecular Mimicry by Neisseria gonorrhoeae.

    Morrill, Sydney R / Saha, Sudeshna / Varki, Ajit P / Lewis, Warren G / Ram, Sanjay / Lewis, Amanda L

    The Journal of infectious diseases

    2023  Volume 228, Issue 11, Page(s) 1610–1620

    Abstract: Bacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome associated with higher risk of infection by Neisseria gonorrhoeae-the cause of gonorrhea. Here we test if one known facet of BV-the presence of bacterial cytolysins-leads to ... ...

    Abstract Bacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome associated with higher risk of infection by Neisseria gonorrhoeae-the cause of gonorrhea. Here we test if one known facet of BV-the presence of bacterial cytolysins-leads to mobilization of intracellular contents that enhance gonococcal virulence. We cloned and expressed recombinant vaginolysin (VLY), a cytolysin produced by the BV-associated bacterium Gardnerella, verifying that it liberates contents of cervical epithelial (HeLa) cells, while vector control preparations did not. We tested if VLY mediates a well-known gonococcal virulence mechanism-the molecular mimicry of host glycans. To evade host immunity, N. gonorrhoeae caps its lipooligosaccharide (LOS) with α2-3-linked sialic acid. For this, gonococci must scavenge a metabolite made inside host cells. Flow cytometry-based lectin-binding assays showed that gonococci exposed to vaginolysin-liberated contents of HeLa cells displayed greater sialic acid capping of their LOS. This higher level of bacterial sialylation was accompanied by increased binding of the complement regulatory protein factor H, and greater resistance to complement attack. Together these results suggest that cytolytic activities present during BV may enhance the ability of N. gonorrhoeae to capture intracellular metabolites and evade host immunity via glycan molecular mimicry.
    MeSH term(s) Female ; Humans ; Neisseria gonorrhoeae ; Gardnerella/metabolism ; HeLa Cells ; N-Acetylneuraminic Acid/metabolism ; Molecular Mimicry ; Bacterial Proteins/genetics ; Vaginosis, Bacterial/microbiology ; Bacteria ; Gonorrhea/microbiology ; Complement Factor H
    Chemical Substances N-Acetylneuraminic Acid (GZP2782OP0) ; Bacterial Proteins ; Complement Factor H (80295-65-4)
    Language English
    Publishing date 2023-09-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad391
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    In stock of ZB MED Cologne/Königswinter

    Uh II Zs.50: Show issues Location:
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  8. Book ; Online: Journal Club discussion of "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China

    Ram, Sanjay / Levitz, Stuart M.

    PEER Liberia Project

    a retrospective cohort study"

    2020  

    Abstract: This presentation presents the following journal article about COVID-19 for analysis and discussion: Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. ... ...

    Abstract This presentation presents the following journal article about COVID-19 for analysis and discussion: Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi:10.1016/S0140-6736(20)30566-3.
    Keywords Coronavirus ; COVID-19 ; risk factors ; mortality ; adult patients ; Wuhan ; China ; Family Medicine ; Infectious Disease ; Medical Education ; Public Health ; Virus Diseases ; covid19
    Publishing date 2020-04-02T07:00:00Z
    Publisher eScholarship@UMMS
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The Modern Epidemic of Syphilis. Reply.

    Ghanem, Khalil G / Ram, Sanjay / Rice, Peter A

    The New England journal of medicine

    2020  Volume 382, Issue 24, Page(s) 2380

    MeSH term(s) Epidemics ; Humans ; Sexual Behavior ; Syphilis
    Language English
    Publishing date 2020-06-08
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2006129
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    Ua VI Zs.34: Show issues Location:
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  10. Article ; Online: The Modern Epidemic of Syphilis.

    Ghanem, Khalil G / Ram, Sanjay / Rice, Peter A

    The New England journal of medicine

    2020  Volume 382, Issue 9, Page(s) 845–854

    MeSH term(s) Algorithms ; Anti-Bacterial Agents/therapeutic use ; Cerebrospinal Fluid/microbiology ; Epidemics ; Female ; Humans ; Male ; Neurosyphilis/diagnosis ; Pregnancy ; Syphilis/diagnosis ; Syphilis/drug therapy ; Syphilis/epidemiology ; Syphilis/physiopathology ; Syphilis Serodiagnosis/methods ; Treponema pallidum/isolation & purification ; United States/epidemiology
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2020-02-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMra1901593
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