Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pro-inflammatory (IL-6, TNFalpha and IL-8) and anti-inflammatory (IL-10) cytokines were determined in weekly samples from 52 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IL-6 increased immediately after transplant peaking at week +3, but IL-8 concentrations were elevated only during week +1. After a slight decrease in week +1, TNF-alpha significantly increased from week +2 and peaked at week +3, whereas, IL-10 values started to rise in week +2 and peaked during week +4. IL-6 and TNF-alpha were positively correlated from week +2 to week +4, and IL-6 levels at week +1 were related with fever and severe stomatitis. Serum levels of IL-6 at week +1 and IL-10 at week +4 were significantly higher in patients with early transplant-related complications, such as fever, severe stomatitis or acute GVHD > or = overall grade II than in those without the complications. We conclude that a high serum IL-6 level at week +1 may be an early predictor of transplant-related complications and that it seems to trigger pro- and anti-inflammatory cytokine release. Kinetic patterns of IL-6 and IL-10 were more exaggerated in those with complications after HSCT.
 ...
PMID:The kinetics of circulating cytokines including IL-6, TNF-alpha, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation. 1175 47

We investigated the primary cellular immune responses to human immunodeficiency virus type 1 (HIV-1) Env and Gag proteins elicited by recombinant vesicular stomatitis viruses (rVSVs). The primary response to Env peaked 5 to 7 days after intraperitoneal vaccination, at which time 40% of CD8(+) cells were Env tetramer positive and activated (CD62L(Lo)). These freshly isolated cells actively lysed target cells pulsed with the p18-I10 peptide and secreted gamma interferon and tumor necrosis factor alpha after stimulation with the Env p18-I10 peptide. The primary response to Env elicited by rVSVs was sixfold higher than that elicited by recombinant vaccinia viruses (rVVs) at 5 days postvaccination. An intranasal route of vaccination with VSV-Env also elicited a strong primary response to Env. The primary immune response to Gag elicited by rVSV peaked 7 days after vaccination, at which time 3% of CD8(+) cells were Gag tetramer positive and CD62L(Lo) and functional by intracellular cytokine staining. This response was eightfold higher than that elicited by rVV expressing Gag. VSV-GagEnv, which expresses both Gag and Env from a single recombinant, also induced strong cytotoxic T-lymphocyte (CTL) responses to both Env and Gag. Our quantitative analyses illustrate the potency of the VSV vector system in CTL induction.
 ...
PMID:High-level primary CD8(+) T-cell response to human immunodeficiency virus type 1 gag and env generated by vaccination with recombinant vesicular stomatitis viruses. 1186 40

Substantial effort has been invested in developing methodologies for efficient gene transfer into human, repopulating, hematopoietic stem cells. Oncoretroviral vectors are limited by the lack of nuclear mitosis in quiescent stem cells during ex vivo transduction, whereas the preintegration complex of lentiviral vectors contains nuclear-localizing signals that permit genome integration without mitosis. We have developed a flexible and versatile system for generating lentiviral vector particles and have pseudotyped such particles with amphotropic, ecotropic, feline endogenous virus (RD114) or vesicular stomatitis virus (VSV-G) envelope proteins. Particles of all four types could be concentrated approximately 100-fold by ultracentrifugation or ultrafiltration. RD114 or amphotropic particles were more efficient than VSV-G-pseudotyped particles at transducing human cord blood CD34(+) cells and clonogenic progenitors within that population. Amphotropic particles transduced cytokine-mobilized, human peripheral blood CD34(+) cells capable of establishing hematopoiesis in immunodeficient mice more efficiently than the other two types of particles. We conclude that the use of amphotropic pseudotyped lentiviral vector particles rather than the commonly used VSV-G-pseudotyped particles should be considered in potential applications of lentiviral vectors for gene transfer into this therapeutically relevant target cell population.
 ...
PMID:Comparison of various envelope proteins for their ability to pseudotype lentiviral vectors and transduce primitive hematopoietic cells from human blood. 1186 13

Lentiviral vectors may improve hematopoietic stem cell (HSC) gene transfer because of their enhanced ability to transduce nondividing cells. However, many studies report efficient transduction only at high multiplicities of infection (MOI). This study reports efficient transduction of human CD34(+) cells with a drug resistance gene allowing post-transduction selection using lentivirus under low-MOI conditions that did not require cytokine stimulation or viral concentration. We used the P140K methylguanine-DNA-methyltransferase mutant (P140K MGMT) as the gene insert into a second-generation lentiviral backbone and triple-plasmid transfection to generate vesicular stomatitis virus (VSV)-G protein-pseudotyped virus. The P140K MGMT gene product, O(6)-alkylguanine-DNA-alkyltransferase (AGT), provides protection from the therapeutic drug combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the wild-type AGT inhibitor O(6)-benzylguanine (BG). Low-speed spinoculation enhanced transduction more than addition of Polybrene or multiple virus exposures. Addition of cytokines was not required. Low-MOI transduction (< or =1) of human CD34(+) and CD34(+) lin(-) cells with P140K MGMT lentivirus resulted in an average 41% and 89% gene transfer rate as assessed by PCR, respectively, and concordant AGT expression that conferred substantial clonogenic survival advantage after BG/BCNU treatment. During in vitro drug selection, 87% of surviving CD34(+) cell-derived colony-forming units (CFU) were transduced. This work shows the potential utility of lentiviral vectors for drug resistance gene transfer to HSCs for the purpose of in vivo selection and marrow protection. Because drug selection will enrich for transduced progenitors, high MOI can be avoided, improving the safety profile of lentiviral gene transfer.
 ...
PMID:Lentiviral transduction of P140K MGMT into human CD34(+) hematopoietic progenitors at low multiplicity of infection confers significant resistance to BG/BCNU and allows selection in vitro. 1194 64

The 4-1BB (a TNFR superfamily member) is an inducible costimulatory molecule that can exert regulatory effects on T cells independently of CD28 stimulation. The in vitro expression of 4-1BB (CD137) is induced following activation of T cells with various stimuli, including anti-TCR mAbs, lectins, and a combination of PMA and ionomycin. To delineate further the physiological role of 4-1BB in immunity, mice deficient in this receptor were generated. These mutant mice developed normally, and were viable and fertile. Humoral responses to vesicular stomatitis virus were comparable with those seen in wild-type mice, whereas the IgG2a and IgG3 isotype responses to keyhole limpet hemocyanin were somewhat reduced in the mutant mice. The 4-1BB-deficient mice demonstrated enhanced T cell proliferation in response to mitogens or anti-CD3 even in the environment of reduced ability to secrete growth-supporting cytokines (IL-2 and IL-4). Although T cells from 4-1BB-deficient mice showed enhanced proliferation, the T cell immune responses of these animals, such as cytokine production and CTL activity, were diminished. In addition, 4-1BB deletion appears to play a role in the regulation of myeloid progenitor cell growth, leading to an increase in these precursor cells in peripheral blood, bone marrow, and spleen.
 ...
PMID:Immune responses in 4-1BB (CD137)-deficient mice. 1202 42

Efficient induction of T cell responses is normally assumed to require both TCR-mediated signaling and engagement of co-stimulatory molecules, in particular CD28. However, the importance of CD28 co-stimulation in induction and maintenance of antiviral T cell responses is not clearly established. For this reason antiviral CD4(+) and CD8(+) T cell responses in CD28-deficient mice were studied using two different viruses [vesicular stomatitis virus and lymphocytic choriomeningitis virus (LCMV)]. Intracellular cytokine staining and/or MHC-peptide tetramers were used to enumerate antigen-specific T cells. In addition, we used DNA constructs encoding viral epitopes to probe the importance of the epitope itself. Our results reveal that while the context of antigen presentation (live virus versus DNA construct) is a critical factor in determining the requirement for CD28 co-stimulation, epitope and virus dose play little if any role. Direct visualization of antigen-specific cells also confirms the notion that CD28 is more critical for the generation of antiviral T(h)1 cells than for T(c)1 cells generated in response to the same virus (LCMV). Most importantly, the present study reveals that CD28 generally is essential for the host to respond optimally over a broad set of conditions, and our results may imply that the relatively CD28 independent activation of LCMV-specific CD8(+) T cells may represent an extreme situation related to the non-cytolytic nature of this virus allowing the delivery of a uniquely strong and prolonged signal 1.
 ...
PMID:Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells. 1209 29

Transcription factors of the interferon regulatory factor (IRF) family have been identified as critical mediators of early inflammatory gene transcription in infected cells. We recently determined that, besides IRF-3 and IRF-7, IRF-5 serves as a direct transducer of virus-mediated signaling. In contrast to that mediated by the other two IRFs, IRF-5-mediated activation is virus specific. We show that, in addition to Newcastle disease virus (NDV) infection, vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) infection activates IRF-5, leading to the induction of IFNA gene subtypes that are distinct from subtypes induced by NDV. The IRF-5-mediated stimulation of inflammatory genes is not limited to IFNA since in BJAB/IRF-5-expressing cells IRF-5 stimulates transcription of RANTES, macrophage inflammatory protein 1 beta, monocyte chemotactic protein 1, interleukin-8, and I-309 genes in a virus-specific manner. By transient- transfection assay, we identified constitutive-activation (amino acids [aa] 410 to 489) and autoinhibitory (aa 490 to 539) domains in the IRF-5 polypeptide. We identified functional nuclear localization signals (NLS) in the amino and carboxyl termini of IRF-5 and showed that both of these NLS are sufficient for nuclear translocation and retention in infected cells. Furthermore, we demonstrated that serine residues 477 and 480 play critical roles in the response to NDV infection. Mutation of these residues from serine to alanine dramatically decreased phosphorylation and resulted in a substantial loss of IRF-5 transactivation in infected cells. Thus, this study defines the regulatory phosphorylation sites that control the activity of IRF-5 in NDV-infected cells and provides further insight into the structure and function of IRF-5. It also shows that the range of IRF-5 immunoregulatory target genes includes members of the cytokine and chemokine superfamilies.
 ...
PMID:Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes. 1213 84

Cell-mediated immunity conferred by CD4+ T helper cells is considered the predominant host defense against mucosal Candida infections, with Thelper (Th1)-type responses associated with resistance to infection and Th2-type responses associated with susceptibility to infection. Oropharyngeal candidiasis, the most common oral opportunistic infection in HIV-infected persons, is associated with a Th2-type cytokine profile in saliva. To obtain more direct evidence for a role of salivary cytokines in susceptibility to oropharyngeal candidiasis during immunosuppression, we evaluated Th1/Th2-type cytokines in the saliva of those with denture stomatitis, a form of oropharyngeal candidiasis not related to immunosuppression. Results showed that HIV-negative denture wearers with and without denture stomatitis demonstrated a mixed Th1/Th2 cytokine profile with no significant differences found between the groups. These results suggest that a local Th cytokine dichotomy in saliva is not associated with susceptibility to denture stomatitis in immunocompetent persons.
 ...
PMID:Salivary cytokine profiles in the immunocompetent individual with Candida-associated denture stomatitis. 1235 13

In this report, the role of STAT4 and local production of interleukin (IL)-12 in the central nervous system (CNS) were examined during experimental vesicular stomatitis virus (VSV) encephalitis. We have previously shown that IL-12 treatment is beneficial both in vitro and in vivo during experimental VSV infection. This inhibition of VSV replication was dependent on the production of nitric oxide (NO) by the neuronal isoform of nitric oxide synthase (NOS-1). In vitro, IL-12 induces the phosphorylation and nuclear localization of STAT4 in neuroblastoma cell lines. STAT4 expression was not required for host survival or clearance of virus during experimental VSV encephalitis. Taken together, these data suggest that while neurons can respond directly to IL-12 in vitro by signaling through STAT4, STAT4 is not required for survival. It is likely that redundant innate host inflammatory cytokine responses compensate for the absence of IL-12 signaling.
 ...
PMID:IL-12, while beneficial, is not essential for the host response to VSV encephalitis. 1245 40

Links have been observed between infections and the development of autoimmunity. Proposed explanations include activation of self-Ag-bearing APC. Using a model system in which transgenic OVA is expressed in enterocytes, we showed that CD8 T cell recognition of cross-presented Ag in gut-associated lymph nodes was tolerogenic. However, concomitant infection with vesicular stomatitis virus encoding OVA abrogated tolerance and induced disease. We now show that following transfer of naive OT-I T cells, the addition of wild-type vesicular stomatitis virus, oral cholera toxin, or CD40 triggering can induce intestinal disease in transgenic mice. Tissue damage accompanied dramatic increases in cytokine release by activated OT-I cells in the intestine. The data indicated that products of antigenically unrelated infections can combine with cross-presented self-Ags on APC to prime autoaggressiveness, independent of additional Ag release. These results help explain how diverse pathogens, lacking any homology to self-proteins, could be causative agents in induction of organ-specific autoimmunity.
 ...
PMID:Cutting edge: inflammatory signals drive organ-specific autoimmunity to normally cross-tolerizing endogenous antigen. 1247 Oct 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>