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Article ; Online: Infection of a Nylon Foil Orbital Implant Due to Fusarium brachygibbosum and Lomentospora prolificans After Intranasal Methamphetamine Use.

Zhou, Paul S / Dermarkarian, Christopher R / Andrade, Rosa M / Tao, Jeremiah P

Ophthalmic plastic and reconstructive surgery

2023 Volume 40, Issue 1, Page(s) e25–e28

Abstract: The authors describe a case of nylon foil implant infection caused by Fusarium brachygibbosum , and Lomentospora prolificans following medial orbital wall fracture repair in the setting of postoperative nasal methamphetamine use. A 61-year-old male ... ...

Abstract	The authors describe a case of nylon foil implant infection caused by Fusarium brachygibbosum , and Lomentospora prolificans following medial orbital wall fracture repair in the setting of postoperative nasal methamphetamine use. A 61-year-old male presented with OS pain and swelling after a physical assault on his face. A CT of maxillofacial bones without contrast showed a moderately comminuted fracture of the medial wall of the left orbit with depression of fracture fragments into the left ethmoid air cells. Six days after repair of the medial wall fracture, the patient returned with a new onset headache, OS pain, and swelling to the left medial canthal area. He reported snorting methamphetamine approximately 48 hours before his current presentation. CT imaging showed fat stranding and soft tissue density in the extraconal space adjacent to the left medial rectus muscle and chronic fracture deformity of lamina papyracea with approximately 4 mm of medial displacement of the fracture fragments. The patient showed little clinical improvement after 48 hours of intravenous antibiotics, which led to the removal of the nylon foil implant by a left orbitotomy. Intraoperative tissue cultures grew coagulase-negative Staphylococcus , F. brachygibbosum , and Lomentospora (Scedosporium) prolificans . The patient was subsequently transitioned to oral clindamycin 600 mg three times daily and voriconazole 200 mg two times daily. To the authors' knowledge, this is the first case report to document an association between snorted methamphetamine and a fungal infection of an orbital implant.
MeSH term(s)	Male ; Humans ; Middle Aged ; Scedosporium ; Nylons ; Orbital Fractures/diagnosis ; Orbital Fractures/etiology ; Orbital Fractures/surgery ; Orbital Implants ; Pain ; Fusarium
Chemical Substances	Nylons
Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632830-1
ISSN	1537-2677 ; 0740-9303
ISSN (online)	1537-2677
ISSN	0740-9303
DOI	10.1097/IOP.0000000000002527
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Article: New drug target in protozoan parasites: the role of thioredoxin reductase.

Andrade, Rosa M / Reed, Sharon L

Frontiers in microbiology

2015 Volume 6, Page(s) 975

Abstract: Amebiasis causes approximately 70,000 deaths annually and is the third cause of death due to parasites worldwide. It is treated primarily with metronidazole, which has adverse side effects, is mutagenic and carcinogenic, and emergence of resistance is an ...

Abstract	Amebiasis causes approximately 70,000 deaths annually and is the third cause of death due to parasites worldwide. It is treated primarily with metronidazole, which has adverse side effects, is mutagenic and carcinogenic, and emergence of resistance is an increasing concern. Unfortunately, better therapeutic alternatives are lacking. Re-purposing of older FDA approved drugs is advantageous to drug discovery since safety and pharmacokinetic effects in humans are already known. In high throughput screening studies, we recently demonstrated that auranofin, a gold containing compound originally approved to treat rheumatoid arthritis, has activity against trophozoites of E. histolytica, the causative agent of amebiasis. Auranofin's anti-parasitic activity is attributed to its monovalent gold molecule that readily inhibits E. histolytica thioredoxin reductase. This anti-oxidant enzyme is the only thiol-dependent flavo-reductase present in E. histolytica. Auranofin has also shown promising activity against other protozoans of significant public health importance. Altogether, this evidence suggests that auranofin has the potential to become a broad spectrum alternative therapeutic agent for diseases with a large global burden.
Language	English
Publishing date	2015-09-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2015.00975
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Article ; Online: Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

Kelly, Emily A / Echeverri Alegre, Jose I / Promer, Katherine / Hayon, Jesica / Iordanov, Roumen / Rangwalla, Khuzaima / Zhang, Jerry J / Fang, Zian / Huang, Cindy / Bittencourt, Cassiana E / Reed, Sharon / Andrade, Rosa M / Bern, Caryn / Clark, Eva H / Whitman, Jeffrey D

The Journal of infectious diseases

2023 Volume 229, Issue 1, Page(s) 198–202

Abstract: Background: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early ... ...

Abstract	Background: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. Methods: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. Results: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. Discussion: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.
MeSH term(s)	Pregnancy ; Humans ; Female ; United States ; Texas/epidemiology ; Trypanosoma cruzi ; Chagas Disease/diagnosis ; Chagas Disease/drug therapy ; Chagas Disease/epidemiology ; California/epidemiology ; Antiparasitic Agents
Chemical Substances	Antiparasitic Agents
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad404
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Article: Acute HIV infection presenting as fulminant meningoencephalitis with massive CSF viral replication.

Andrade, Rosa M / Torriani, Francesca J / Ellis, Ronald J

Neurology. Clinical practice

2014 Volume 4, Issue 3, Page(s) 256–259

Abstract: A 22-year-old man presented to the emergency department with 10 days of malaise, generalized rash, sore throat, oral ulcers, headache, nausea, and vomiting. On examination he had fever (101.5°F), hepatosplenomegaly, generalized maculopapular rash, and ... ...

Abstract	A 22-year-old man presented to the emergency department with 10 days of malaise, generalized rash, sore throat, oral ulcers, headache, nausea, and vomiting. On examination he had fever (101.5°F), hepatosplenomegaly, generalized maculopapular rash, and lymphadenopathy. He rapidly became obtunded, requiring intubation. Initial laboratory studies showed mild transaminitis, increased lactate dehydrogenase, and 4,600 leukocytes per μL with 61% bands and 18% lymphocytes. Bacterial and fungal blood cultures were negative as well as a rapid HIV test, additional serologies (including rapid plasma reagin and
Language	English
Publishing date	2014-02-10
Publishing country	United States
Document type	Case Reports
ZDB-ID	2645818-4
ISSN	2163-0933 ; 2163-0402
ISSN (online)	2163-0933
ISSN	2163-0402
DOI	10.1212/CPJ.0000000000000037
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Article ; Online: Auranofin Resistance in

Ma, Christopher I / Tirtorahardjo, James A / Jan, Sharon / Schweizer, Sakura S / Rosario, Shawn A C / Du, Yanmiao / Zhang, Jerry J / Morrissette, Naomi S / Andrade, Rosa M

Frontiers in cellular and infection microbiology

2021 Volume 11, Page(s) 618994

Abstract: Auranofin, a reprofiled FDA-approved drug originally designed to treat rheumatoid arthritis, has emerged as a promising anti-parasitic drug. It induces the accumulation of reactive oxygen species (ROS) in parasites, ... ...

Abstract	Auranofin, a reprofiled FDA-approved drug originally designed to treat rheumatoid arthritis, has emerged as a promising anti-parasitic drug. It induces the accumulation of reactive oxygen species (ROS) in parasites, including
MeSH term(s)	Animals ; Auranofin/pharmacology ; Parasites ; Reactive Oxygen Species ; Thioredoxin-Disulfide Reductase/genetics ; Toxoplasma/genetics
Chemical Substances	Reactive Oxygen Species ; Auranofin (3H04W2810V) ; Thioredoxin-Disulfide Reductase (EC 1.8.1.9)
Language	English
Publishing date	2021-03-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2021.618994
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Article ; Online: Auranofin is highly efficacious against Toxoplasma gondii in vitro and in an in vivo experimental model of acute toxoplasmosis.

Andrade, Rosa M / Chaparro, Juan D / Capparelli, Edmund / Reed, Sharon L

PLoS neglected tropical diseases

2014 Volume 8, Issue 7, Page(s) e2973

Abstract: Background: The mainstay of toxoplasmosis treatment targets the folate biosynthetic pathways and has not changed for the last 50 years. The activity of these chemotherapeutic agents is restricted to one lifecycle stage of Toxoplasma gondii, they have ... ...

Abstract	Background: The mainstay of toxoplasmosis treatment targets the folate biosynthetic pathways and has not changed for the last 50 years. The activity of these chemotherapeutic agents is restricted to one lifecycle stage of Toxoplasma gondii, they have significant toxicity, and the impending threat of emerging resistance to these agents makes the discovery of new therapies a priority. We now demonstrate that auranofin, an orally administered gold containing compound that was FDA approved for treatment of rheumatoid arthritis, has activity against Toxoplasma gondii in vitro (IC50 = 0.28 µM) and in vivo (1 mg/kg). Methods/principal findings: Replication within human foreskin fibroblasts of RH tachyzoites was inhibited by auranofin. At 0.4 µM, auranofin inhibited replication, as measured by percent infected fibroblasts at 24 hrs, (10.94% vs. 24.66% of controls; p = 0.0003) with no effect on parasite invasion (16.95% vs. 12.91% p = 0.4331). After 18 hrs, 62% of extracellular parasites treated with auranofin were non-viable compared to control using an ATP viability assay (p = 0.0003). In vivo, a previously standardized chicken embryo model of acute toxoplasmosis was used. Fourteen day old chicken embryos were injected through the chorioallantoic vein with 1×104 tachyzoites of the virulent RH strain. The treatment group received one dose of auranofin at the time of inoculation (1 mg/kg estimated body weight). On day 5, auranofin-treated chicken embryos were 100% protected against death (p = 0.0002) and had a significantly reduced parasite load as determined by histopathology, immunohistochemistry and by the number of parasites quantified by real-time PCR. Conclusions: These results reveal in vitro and in vivo activity of auranofin against T. gondii, suggesting that it may be an effective alternative treatment for toxoplasmosis.
MeSH term(s)	Animals ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/therapeutic use ; Auranofin/pharmacology ; Auranofin/therapeutic use ; Cell Survival/drug effects ; Cells, Cultured ; Chick Embryo ; Disease Models, Animal ; Drug Repositioning ; Fibroblasts/parasitology ; Histocytochemistry ; Humans ; Immunohistochemistry ; Inhibitory Concentration 50 ; Parasite Load ; Parasitic Sensitivity Tests ; Real-Time Polymerase Chain Reaction ; Toxoplasma/drug effects ; Toxoplasma/growth & development ; Toxoplasma/physiology ; Toxoplasmosis/drug therapy ; Treatment Outcome
Chemical Substances	Antiprotozoal Agents ; Auranofin (3H04W2810V)
Language	English
Publishing date	2014-07-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0002973
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Article ; Online: Two key cathepsins, TgCPB and TgCPL, are targeted by the vinyl sulfone inhibitor K11777 in in vitro and in vivo models of toxoplasmosis.

Chaparro, Juan D / Cheng, Timmy / Tran, Uyen Phuong / Andrade, Rosa M / Brenner, Sara B T / Hwang, Grace / Cohn, Shara / Hirata, Ken / McKerrow, James H / Reed, Sharon L

PloS one

2018 Volume 13, Issue 3, Page(s) e0193982

Abstract: Although toxoplasmosis is one of the most common parasitic infections worldwide, therapeutic options remain limited. Cathepsins, proteases that play key roles in the pathogenesis of toxoplasmosis and many other protozoan infections, are important ... ...

Abstract	Although toxoplasmosis is one of the most common parasitic infections worldwide, therapeutic options remain limited. Cathepsins, proteases that play key roles in the pathogenesis of toxoplasmosis and many other protozoan infections, are important potential therapeutic targets. Because both TgCPB and TgCPL play a role in T. gondii invasion, we evaluated the efficacy of the potent, irreversible vinyl sulfone inhibitor, K11777 (N-methyl-piperazine-Phe-homoPhe-vinylsulfone-phenyl). The inhibitor's toxicity and pharmacokinetic profile have been well-studied because of its in vitro and in vivo activity against a number of parasites. We found that it inhibited both TgCPB (EC50 = 114 nM) and TgCPL (EC50 = 71 nM) in vitro. K11777 also inhibited invasion of human fibroblasts by RH tachyzoites by 71% (p = 0.003) and intracellular replication by >99% (p<0.0001). In vivo, a single dose of K11777 led to 100% survival of chicken embryos in an model of acute toxoplasmosis (p = 0.015 Cox regression analysis). Therefore, K11777 shows promise as a novel therapeutic agent in the treatment of toxoplasmosis, and may prove to be a broadly effective anti-parasitic agent.
MeSH term(s)	Animals ; Antiparasitic Agents/pharmacology ; Cathepsins/metabolism ; Chickens ; Dipeptides/pharmacology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Humans ; Phenylalanine/analogs & derivatives ; Piperazines ; Protozoan Proteins/metabolism ; Sulfones/antagonists & inhibitors ; Tosyl Compounds ; Toxoplasmosis/drug therapy ; Toxoplasmosis/metabolism ; Vinyl Compounds/pharmacology
Chemical Substances	Antiparasitic Agents ; Dipeptides ; Piperazines ; Protozoan Proteins ; Sulfones ; Tosyl Compounds ; Vinyl Compounds ; N-pip-phenylalanine-homophenylalanine-vinyl sulfone phenyl (320A4L58IZ) ; Phenylalanine (47E5O17Y3R) ; divinyl sulfone (5PFN71LP8M) ; Cathepsins (EC 3.4.-)
Language	English
Publishing date	2018-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0193982
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Article: CD40-TRAF6 and autophagy-dependent anti-microbial activity in macrophages.

Subauste, Carlos S / Andrade, Rosa M / Wessendarp, Matthew

Autophagy

2007 Volume 3, Issue 3, Page(s) 245–248

Abstract: A fundamental question in host-pathogen interaction is to determine if the immune system activates fusion with the lysosomes to eradicate pathogens. We recently reported that this task is accomplished by the interaction between CD40 expressed on ... ...

Abstract	A fundamental question in host-pathogen interaction is to determine if the immune system activates fusion with the lysosomes to eradicate pathogens. We recently reported that this task is accomplished by the interaction between CD40 expressed on macrophages and CD154 expressed on activated CD4+ T cells. CD40 stimulation of macrophages induces vacuole-lysosome fusion through autophagy and results in killing of the obligate intracellular pathogen Toxoplasma gondii. This response is independent of IFN-gamma, STAT1 and p47 GTPases. We now report that vacuole-lysosome fusion is dependent on synergy between TRAF6 signaling downstream of CD40 and TNF-alpha. These studies identified a new paradigm by which T cells eradicate an intracellular pathogen within macrophages.
MeSH term(s)	Amino Acid Sequence ; Animals ; Autophagy/immunology ; CD40 Antigens/genetics ; CD40 Antigens/immunology ; CD40 Ligand/genetics ; CD40 Ligand/immunology ; Humans ; Lysosomes/metabolism ; Macrophages/cytology ; Macrophages/immunology ; Macrophages/parasitology ; Mice ; Molecular Sequence Data ; Recombinant Fusion Proteins ; Signal Transduction ; T-Lymphocytes/immunology ; TNF Receptor-Associated Factor 6/metabolism ; Toxoplasma/immunology ; Tumor Necrosis Factor-alpha/metabolism ; Vacuoles/metabolism
Chemical Substances	CD40 Antigens ; Recombinant Fusion Proteins ; TNF Receptor-Associated Factor 6 ; Tumor Necrosis Factor-alpha ; CD40 Ligand (147205-72-9)
Language	English
Publishing date	2007-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.4161/auto.3717
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Article ; Online: HIV-1 inhibits autophagy in bystander macrophage/monocytic cells through Src-Akt and STAT3.

Van Grol, Jennifer / Subauste, Cecilia / Andrade, Rosa M / Fujinaga, Koh / Nelson, Julie / Subauste, Carlos S

PloS one

2010 Volume 5, Issue 7, Page(s) e11733

Abstract: Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act ... ...

Abstract	Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act upstream of autophagy proteins. Little is known about the role of altered regulatory signaling in disorders associated with defective autophagy. In particular, it is not known if pathogens inhibit autophagy by modulation of upstream regulatory pathways. Cells infected with HIV-1 blocked rapamycin-induced autophagy and CD40-induced autophagic killing of Toxoplasma gondii in bystander (non-HIV-1 infected) macrophage/monocytic cells. Blockade of autophagy was dependent on Src-Akt and STAT3 triggered by HIV-1 Tat and IL-10. Neutralization of the upstream receptors VEGFR, beta-integrin or CXCR4, as well as of HIV-1 Tat or IL-10 restored autophagy in macrophage/monocytic cells exposed to HIV-1-infected cells. Defective autophagic killing of T. gondii was detected in monocyte-derived macrophages from a subset of HIV-1(+) patients. This defect was also reverted by neutralization of Tat or IL-10. These studies revealed that a pathogen can impair autophagy in non-infected cells by activating counter-regulatory pathways. The fact that pharmacologic manipulation of cell signaling restored autophagy in cells exposed to HIV-1-infected cells raises the possibility of therapeutic manipulation of cell signaling to restore autophagy in HIV-1 infection.
MeSH term(s)	Autophagy/drug effects ; CD40 Antigens/pharmacology ; Cell Line ; Cells, Cultured ; HIV-1/physiology ; Humans ; Immunoblotting ; Macrophages/drug effects ; Macrophages/physiology ; Monocytes/drug effects ; Monocytes/physiology ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Sirolimus/pharmacology ; Toxoplasma/immunology
Chemical Substances	CD40 Antigens ; STAT3 Transcription Factor ; STAT3 protein, human ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2010-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0011733
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Article: CD154 activates macrophage antimicrobial activity in the absence of IFN-gamma through a TNF-alpha-dependent mechanism.

Andrade, Rosa M / Wessendarp, Matthew / Subauste, Carlos S

Journal of immunology (Baltimore, Md. : 1950)

2003 Volume 171, Issue 12, Page(s) 6750–6756

Abstract: Protection against certain intracellular pathogens can take place in the absence of IFN-gamma through mechanisms dependent on TNF-alpha. In this regard, patients with partial defect in IFN-gamma receptor 1 are not susceptible to toxoplasmosis. Thus, we ... ...

Abstract	Protection against certain intracellular pathogens can take place in the absence of IFN-gamma through mechanisms dependent on TNF-alpha. In this regard, patients with partial defect in IFN-gamma receptor 1 are not susceptible to toxoplasmosis. Thus, we used a model of Toxoplasma gondii infection to investigate whether CD154 modulates IFN-gamma-independent mechanisms of host protection. Human monocyte-derived macrophages treated with recombinant CD154 exhibited increased anti-T. gondii activity. The number of tachyzoites per 100 macrophages at 20 h postinfection was lower in CD154-treated macrophages compared with controls. This was accompanied by a decrease in the percentage of infected cells in CD154-treated macrophages at 20 h compared with 1 h postinfection. CD154-bearing cells also induced antimicrobial activity in T. gondii-infected macrophages. CD154 enhanced macrophage anti-T. gondii activity independently of IFN-gamma. TNF-alpha mediated the effects of CD154 on macrophage anti-T. gondii activity. CD154 increased TNF-alpha production by T. gondii-infected macrophages, and neutralization of TNF-alpha inhibited the effect of CD154 on macrophage anti-T. gondii activity. These results demonstrate that CD154 triggers TNF-alpha-dependent antimicrobial activity in macrophages and suggest that CD154 regulates the mechanisms of host protection that take place when IFN-gamma signaling is deficient.
MeSH term(s)	Adjuvants, Immunologic/physiology ; Animals ; CD40 Ligand/physiology ; Cells, Cultured ; Dose-Response Relationship, Immunologic ; Humans ; Interferon-gamma/deficiency ; Interferon-gamma/physiology ; Macrophage Activation/immunology ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/parasitology ; Monocytes/immunology ; Monocytes/parasitology ; Recombinant Proteins/pharmacology ; Signal Transduction/immunology ; Toxoplasma/growth & development ; Toxoplasma/immunology ; Tumor Necrosis Factor-alpha/metabolism ; Tumor Necrosis Factor-alpha/physiology
Chemical Substances	Adjuvants, Immunologic ; Recombinant Proteins ; Tumor Necrosis Factor-alpha ; CD40 Ligand (147205-72-9) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2003-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.171.12.6750
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