Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induction of an immunological antitumor response capable of eradicating metastatic tumors is the ultimate goal of immunotherapy. We have recently shown that this can be achieved by interleukin 2 (IL-2) therapy directed to the tumor microenvironment by a recombinant antibody-IL-2 fusion protein. It is not known, however, whether this curative treatment is associated with a predominance of T cells carrying specific T cell receptor variable beta regions (TCRBV) or the presence of clonally expanded T cells. To address this question, we have used a quantitative reverse transcriptase-coupled PCR method to analyze the TCRBV region repertoire in tumor-infiltrating lymphocytes of treated and untreated animals. As controls the TCRBV region repertoire was analyzed in blood and skin from disease-free animals. The results indicate an overexpression of TCRBV5 in the tumors of all treated mice and an additional overexpression of individual regions in each tumor. Direct sequencing of these TCRBV regions did not reveal any evidence of clonal expansions. However, since clonal expansions could exist as subpopulations in highly expressed regions, not detectable by direct sequencing, a denaturing gradient gel electrophoresis assay was used for clonal analysis of TCRBV PCR products. Denaturing gradient gel electrophoresis analysis of selected TCRBV regions revealed the presence of clonotypic T cells in tumors from both treated and untreated animals. These data indicate that targeted IL-2 therapy in this model does not induce clonal T cell responses de novo, rather it acts as an activator for an already existing population of clonotypic T cells.
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PMID:Activation of preexisting T cell clones by targeted interleukin 2 therapy. 967 56

Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 micrograms/mouse/d for 3 or 7 d. In non-treated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-gamma]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.
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PMID:Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection. 1056 55

While the effectiveness of conventional antiviral treatment is well proven, its limitations are becoming more and more evident. New approaches are resulting from the "decoding" of the pathogenesis of HIV infection. Thus, for example, experimental studies are looking at drug-induced blockade of the co-receptors necessary for the infection of the target cells. Treatment can be applied at all stages of viral replication. So far, reverse transcriptase and protease inhibitors have been employed. Other strategies are aimed at immunostimulation (e.g. with interleukin 2) and immunosuppression (cortisone, hydroxyurea). The development of therapeutic vaccines is difficult, but prophylactic vaccines hold out greater promise; field trials are underway.
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PMID:[Pathogenesis of HIV infection as the key to eradication? New therapeutic approaches]. 1086 8

Because prevention of heterosexual HIV transmission is not always possible, it is important to develop effective strategies of postexposure prophylaxis (PEP). Since in vivo comparison of drug potency is difficult, we developed an in vitro model with cells resembling primary targets during sexual transmission: monocyte-derived dendritic cells (MO-DCs), Langerhans cells (MO-LCs), and resting autologous CD4(+) T cells. Nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively) were evaluated for their antiviral activity, when added immediately after infection or at a later time point. In parallel, their immune-suppressive effect was examined by measuring inhibition of mixed MO-DC/allogeneic CD4(+) T cell cultures. Most RTIs potently inhibited HIV replication, even if added 24 hr after infection (representing PEP). The sensitivity to antiretroviral drugs was similar in HIV-infected MO-DCs and MO-LCs, but decreased in cocultures with resting autologous CD4(+) T cells. The NNRTIs efavirenz and UC-781 as well as the NRTIs AZT, 3TC, and d4T showed a similar high potency in MO-DC plus autologous CD4(+) T cell cocultures as compared with CEM T cells, whereas their activity in phytohemagglutinin/interleukin 2 (PHA/IL-2)-activated CD4(+) T cells was lower. The dideoxynucleoside RTI abacavir as well as the phosphonates (R)-PMPA and PMEA were more active in infected MO-DCs as compared with either CEM T cells or PHA/IL-2 activated CD4(+) T cells. Infection in cocultures of MO-DCs and autologous CD4(+) T cells could be aborted in a proportion of the cultures, with high concentrations of PMEA and/or efavirenz, but not with AZT. Suppressive activity in mixed leukocyte cultures was observed only at very high concentrations of RTI. Our data suggest that cocultures of MO-DCs and autologous CD4(+) T cells can be used as a possible in vitro model to explore protocols for PEP after sexual HIV transmission.
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PMID:Activity of reverse transcriptase inhibitors in monocyte-derived dendritic cells: a possible in vitro model for postexposure prophylaxis of sexual HIV transmission. 1239 48

The development of effective, safe vaccines for human and bovine respiratory syncytial virus (RSV) has been problematic. Inactivated RSV vaccines are of variable efficacy; poor efficacy may be related to induction of ineffective cell-mediated immunity (CMI). To characterize CMI in calves vaccinated with formalin inactivated (FI) BRSV, 11 calves were vaccinated twice with FI-BRSV (n=5) or mock vaccine (n=6) at a 2 week interval and challenged 1 month later. Prior to challenge a cannula was placed in the efferent lymphatic of the caudal mediastinal lymph node of each calf; lymph derived lymphocytes (LDL) were collected for analysis of CMI. Cytotoxic T lymphocyte (CTL) activity by LDL and/or peripheral blood mononuclear cells (PBMC) was measured by 51Cr release on days 5, 7, 9, and 10 post-challenge. Messenger RNA for interferon gamma (IFN-gamma), interleukin 2 (IL-2) and IL-4 was measured on days 0-10 by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA of LDL. BRSV-specific IFN-gamma production by PBMC was measured on days 0 and 10 by ELISA. Clinical signs and postmortem changes following challenge were evaluated. There was no difference between groups in clinical signs, postmortem changes, CTL activity, cytokine message expression, or IFN-gamma production. For both groups, percentage lysis by CTL peaked on days 7-10 and ranged from 11 to 25%. Failure of vaccination to prevent disease following challenge was likely associated with failure to prime for improved CMI responses.
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PMID:Cytotoxic T lymphocyte activity and cytokine expression in calves vaccinated with formalin-inactivated bovine respiratory syncytial virus prior to challenge. 1465 42

Trefoil family factor 2 (TFF2), also known as spasmolytic peptide, is a low-molecular-weight protein that is upregulated in gastric tissues infected with Helicobacter or having other inflammatory conditions, but a precise function is yet to be elucidated. The role of TFF2 in the development of gastritis, colitis, and inflammatory cytokine responses was examined both in vivo and in vitro using wild-type and TFF2 knockout mice. TFF2 knockout and wild-type mice were infected with Helicobacter felis (H. felis) to induce gastritis. Colitis was induced in TFF2 knockout and wild-type mice by administering dextran sodium sulfate (DSS) in drinking water. Histopathology, clinical disease (colitis), and antibody levels (H. felis) were examined. TFF2 expression in tissues was determined by reverse transcriptase PCR, and the inflammatory and proliferative responses of TFF2-expressing macrophages and spleen cells were examined by cytokine enzyme-linked immunosorbent assay, thymidine incorporation, and gene array studies. TFF2 knockout mice have increased susceptibility to H. felis-induced gastritis, with enhanced gastric inflammation. They were also more susceptible to DSS-induced colitis, with prolonged colonic hemorrhage and persistent weight loss. Remarkably, TFF2 expression was not limited to the gastrointestinal tract, as suggested in previous studies, but was also present in macrophages and lymphocytes. The inflammatory and proliferative responses of these immune cell types were dysregulated in TFF2 knockout mice. TFF2-/- cells were hyperresponsive to interleukin 1 beta stimulation but showed normal responses to lipopolysaccharide, suggesting a specific role for TFF2 in interleukin 1 receptor but not Toll-like receptor 4 signaling via their Toll-interleukin 1 resistance domains. TFF2-/- lymphocytes also produced higher levels of interleukin 2 than wild-type cells. Thus, TFF2 was expressed in the gastrointestinal cells and in immune cells and was a negative regulator of gastrointestinal inflammation and immune cell cytokine responses. Our studies suggest that TFF2 not only controls gastrointestinal repair but also regulates mononuclear cell inflammatory responses.
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PMID:Trefoil family factor 2 is expressed in murine gastric and immune cells and controls both gastrointestinal inflammation and systemic immune responses. 1710 60

Biphalin, a dimeric enkephalin analog, is under investigation as a potential, long-lasting medication of pain associated with chronic diseases, like cancer or AIDS. The role of cytokines, and splenocytes in anti-Friend leukemia virus (FLV) activity of biphalin, a synthetic opioid, and AZT was investigated in vitro. Mouse splenocytes inhibited FLV replication in Mus dunni (Dunni) cells when they were added to the cell culture. This inhibitory effect of splenocytes also was evident when cells were combined with biphalin and AZT as measured using a focus-forming assay. Under cell-free conditions, recombinant interferon gamma (IFNgamma), interleukin 2 (IL-2) and IL-4 directly inhibited the FLV reverse transcriptase (RT) activity by 27% to 36%. IFNgamma at 0.005 pg to 500 ng inhibited FLVRT activity by 61% to 80%. Acombination of 250 ng IFNgamma and 50 mug biphalin resulted in a 94% reduction of FLVRT activity, as compared with 61% inhibition by IFNgamma alone. The combination of AZT and IFNgamma, IL-2 or IL-4 also induced a stronger suppression of FLV RT activity than either cytokine or AZT used alone. In addition, cloned RT from Moloney murine leukemia virus (MMLV) was directly sensitive to inhibition by biphalin. Thus, the anti-FLV effects of splenocytes in combination with biphalin and AZT in cell culture are likely mediated to a large degree by the direct effect of cytokines. This antiviral activity of splenocytes or cytokines combined with chemotherapy, biphalin, and/or AZT, could be used as a complementary therapy to current approaches for retroviral infection and benefit acquired immunodeficiency syndrome (AIDS) patients. In conclusion, biphalin applied primarily as a new medicine for chronic pain treatment in AIDS patients may play a significant beneficial role as a component of antiviral HIV multidrug therapies.
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PMID:Molecular assessment of the potential combination therapy of cytokines with biphalin and AZT for Friend leukemia virus infection in vitro. 1844 80

High prevalence of hepatitis B virus (HBV) infection in China offers a unique setting to examine HBV's influence on the presentation of dengue fever. In 398 patients admitted for suspected dengue fever, 89% (353/398) were positive for dengue IgM antibodies. Among dengue-infected patients, 8% (29/353) had chronic HBV co-infection. Only dengue virus serotype 1 was identified by virus isolation and reverse transcriptase-polymerase chain reaction assays. No case of dengue hemorrhagic fever/dengue shock syndrome was diagnosed. In addition to routine clinical tests, interleukin 2 (IL-2), IL-4, IL-6, IL-10, interferon gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) levels were measured in the sera of 95% (334/353) of dengue-infected subjects as well as controls. Surprisingly, HBV/dengue co-infected patients made less IL-6 (P < 0.05) and TNFalpha (P < 0.05) than patients with only dengue infection. Similar levels of IL-4, IL-10, and IFNgamma were found in both groups. Thus, HBV co-infection seems to alter the cytokine production pattern when patients contract dengue infection.
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PMID:Unique impacts of HBV co-infection on clinical and laboratory findings in a recent dengue outbreak in China. 1868 15

Induction of an antigenically broad and vigorous primary T-cell immune response by myeloid dendritic cells (DC) in blood and tissues could be important for an effective prophylactic or therapeutic vaccine to human immunodeficiency virus type 1 (HIV-1). Here we show that a primary CD8(+) T-cell response can be induced by HIV-1 peptide-loaded DC derived from blood monocytes of HIV-1-negative adults and neonates (moDC) and by Langerhans cells (LC) and interstitial, dermal-intestinal DC (idDC) derived from CD34(+) stem cells of neonatal cord blood. Optimal priming of single-cell gamma interferon (IFN-gamma) production by CD8(+) T cells required CD4(+) T cells and was broadly directed to multiple regions of Gag, Env, and Nef that corresponded to known and predicted major histocompatibility complex class I epitopes. Polyfunctional CD8(+) T-cell responses, defined as single-cell production of more than one cytokine (IFN-gamma, interleukin 2, or tumor necrosis factor alpha), chemokine (macrophage inhibitory factor 1beta), or cytotoxic degranulation marker CD107a, were primed by moDC, LC, and idDC to HIV-1 Gag and reverse transcriptase epitopes, as well as to Epstein-Barr virus and influenza A virus epitopes. Thus, three major types of blood and tissue myeloid DC targeted by HIV-1, i.e., moDC, LC, and idDC, can prime multispecific, polyfunctional CD8(+) T-cell responses to HIV-1 and other viral antigens.
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PMID:Primary human immunodeficiency virus type 1-specific CD8+ T-cell responses induced by myeloid dendritic cells. 1935 76

The nephrotic syndrome is a rare complication of allogeneic stem cell transplantation (alloHSCT). We present two cases of nephrotic syndrome during chronic graft-versus-host disease (GvHD) involving altered cytokine gene expression in renal tissue. A patient with acute lymphatic leukemia demonstrated nephrotic syndrome due to minimal change disease as a marker of chronic GvHD. A patient with acute lymphoblastic leukemia suffered from severe nephrotic syndrome due to membranous glomerulopathy. In the two presented cases of GvHD-linked nephrotic syndrome, increased cytokine gene expression [tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interferon gamma (IFN-gamma), interleukin 2 (IL-2), IL-6, and IL-10] assessed using semiquantitative evaluation with reverse transcriptase polymerase chain reaction (RT-PCR) in situ on renal biopsy was observed.
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PMID:Glomerular lesion and increased cytokine gene expression in renal tissue in patients with decompensated nephrotic syndrome due to chronic GvHD. 2044 93


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