Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Bovine leukemia virus (BLV) infection of rabbits provides a safe and relatively inexpensive in vivo mammalian system for the study of the mechanisms controlling expression of a unique group of lymphotropic retroviruses. This group of viruses, which includes C-type human T-lymphotropic virus types I and II and lentiviruslike human immunodeficiency virus type 1, possesses genes coding for "trans-activating" products. Rabbits experimentally inoculated with BLV became persistently infected, as demonstrated by a number of tests. All BLV-inoculated rabbits developed persistent serum antibody to BLV. Furthermore, all BLV-inoculated rabbits had peripheral blood mononuclear cells which, when stimulated, expressed the virus, as demonstrated by viral induction of syncytium formation in a BLV-susceptible fibroblast line. The presence of BLV in circulating cells was confirmed by using peripheral blood mononuclear cells from randomly selected BLV-inoculated rabbits, which showed the presence of viral reverse transcriptase activity, BLV transcriptional activity, or BLV proviral DNA. Additional tests showed that infected lymphocytes maintained in culture with recombinant human interleukin-2 formed multinucleated giant cells and produced virus when incubated in cytokine-containing medium. BLV-infected rabbits also showed alterations in several parameters associated with immunity, beginning 6 months after inoculation. Thirty-eight percent of infected rabbits developed abnormally low T-cell responses, as measured by phytolectin stimulation, and T-cell responses cycled between normal and abnormally low over a period of 20 to 24 months. Forty-four percent of rabbits infected for longer than 12 months suffered from recurrent conjunctivitis and rhinitis. By 24 months postinoculation, 28% of infected rabbits were dead or were killed because of poor clinical condition.
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PMID:Persistent infection of rabbits with bovine leukemia virus associated with development of immune dysfunction. 255 35

The met proto-oncogene receptor tyrosine kinase has been identified as a receptor for hepatocyte growth factor (HGF)/scatter factor (SF). HGF/SF is a multifunctional cytokine that stimulates mitogenesis, dissociation, and motility of a broad spectrum of epithelial and endothelial cells in culture, promotes the progression of carcinoma cells to a more invasive phenotype, and acts as a morphogenic factor for tubular epithelia. HGF/SF is predominantly expressed by mesenchymal cells, whereas the met/HGF/SFR is predominantly expressed by epithelial and carcinoma cells in culture. We have shown by Northern analyses that the met/HGF/SFR is expressed in many adult mouse tissues. To elucidate the normal physiologic role for the met/HGF/SFR and the possible pathologic consequences of deregulation of this pathway, we have examined the expression of the met/HGF/SFR in adult mouse tissue by in situ hybridization. We show that the met/HGF/SFR is generally expressed in epithelia, including hepatocytes, epithelial cells that line the proximal and distal convoluted tubules of the kidney, epithelia of stomach, esophagus, uterus, lung and skin, as well as in granulosa cells of developing and mature oocytes. By reverse transcriptase PCR amplification, we show that the HGF/SF gene is expressed at low levels in many of these tissues. Our data support a possible role for the met/HGF/SFR in epithelial cell growth and tissue organization.
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PMID:Expression of the hepatocyte growth factor/scatter factor receptor tyrosine kinase is localized to epithelia in the adult mouse. 747 19

The antiviral drugs didanosine (ddI) and zidovudine (AZT), synthetic nucleoside analogs, have been used in the treatment of acquired immunodeficiency syndrome (AIDS). Although clinical use of zidovudine (AZT) is still widely used, it is associated with the development of virus disease resistance and toxicity to the hematopoietic system. Alternative nucleoside reverse transcriptase derivatives such as didanosine (ddI) have been developed in order to reduce the incidence of virus disease resistance and hematological toxicity. We report here studies designed to ev evaluate the toxicity profile comparing didanosine (ddI) with zidovudine (AZT) when used alone or in combination with normal non-adherent, T-cell depleted human marrow cells plated in the presence or absence of the human cytokine fusion protein of granulocyte-macrophage colony stimulating factor and interleukin-3 (PIXY321). As expected, didanosine (ddI) was less toxic for human hematopoietic progenitor cells, i.e., CFU-GEMM, CFU-GM, CFU-Meg, and BFU-E than zidovudine. Toxicity was additive when didanosine (ddI) and zidovudine (AZT) were combined. In the absence of drugs PIXY321 colony formation was increased for all progenitor cells cultured. In the presence of didanosine (ddI) or zidovudine (AZT), either as single-agents or combined, PIXY321 reduced toxicity significantly. These results demonstrate PIXY321 is an effective cytokine capable of reversing the toxicity associated with anti-viral drugs when used in vitro where didanosine (ddI) is less toxic than zidovudine (AZT); however their suppression of hematopoietic progenitors is additive when combined.
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PMID:Influence of human granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein (PIXY321) on the hematopoietic toxicity associated with anti-viral drugs (zidovudine and didanosine) in vitro using normal human marrow cells. 747 1

Fine needle aspiration of renal transplants is a safe effective means of obtaining intragraft material for diagnostic evaluation of transplant dysfunction in the first 3-6 months post engraftment. Aspiration can be performed daily as an outpatient to assess causes of renal insufficiency and response to therapeutic intervention. Aspiration also provides a unique tool for the investigation of pathogenetic mechanisms in acute rejection; samples can be subjected to reverse transcriptase-polymerase chain reaction with quantitation of cytokine gene expression. We have utilized this technique to demonstrate the strong, likely causal, relationship between gamma-interferon and acute rejection. The ability to perform aspirates frequently affords an opportunity to map the cytokine cascade prior to and during episodes of acute rejection. This may identify new areas for therapeutic intervention during the process of rejection.
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PMID:Renal transplant fine needle aspiration and cytokine gene expression. 749 89

A cytokine-mediated excessive increase in nitric oxide (NO) by macrophages or glial cells via an inducible isoform of NO synthase (iNOS) has been proposed to play an important role in demyelinating diseases. To further investigate the role of iNOS in demyelination, experimental allergic encephalomyelitis (EAE), a known animal model of multiple sclerosis (MS) in mice, was chosen in this study. A semiquantitative reverse transcriptase-polymerase chain reaction (RT/PCR) analysis revealed an increase in the mRNA levels of iNOS and cytokines known to induce iNOS or inflammatory cytokines (interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-6, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta) in the spinal cord corresponding to the severity of the disease without significant change in the mRNA levels of immunoregulatory cytokines (IL-4, IL-10 and transforming growth factor (TGF)-beta) during the course of EAE. An immunohistochemical examination of the spinal cord using an iNOS-specific antibody showed iNOS-positive cells to be mainly inflammatory cells with a higher frequency of iNOS-positive cells at the peak of EAE than in the early phase. These iNOS-positive cells at the peak appeared to be composed of infiltrating macrophages and most of them were located in the necrotic area. These results suggested that cytokine-induced excessive NO via iNOS by macrophages caused tissue damage in the central nervous system in EAE.
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PMID:Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis. 749 86

Human immunodeficiency virus (HIV) infection leads to a progressive loss of CD4+ T helper (Th) type 1 cell-mediated immunity that is associated with defective in vitro CD4+ T cell proliferation and abnormal T cell death by apoptosis in response to T cell receptor (TCR) stimulation. Quantification of interleukin (IL)-2, interferon gamma, IL-4, IL-5, and IL-10 secretion by immunoassays, and of interferon gamma, IL-4 and IL-10 messenger RNA expression by competitive reverse transcriptase polymerase chain reaction after in vitro stimulation of the TCR revealed a similar Th1 cytokine profile in T cells from HIV-infected persons and from controls. These data indicated that the loss of CD4+ Th1 cell function in HIV-infected persons is not related to a Th1 to Th2 cytokine switch as previously proposed, but to a process of activation-induced death of CD4+ Th1 cells. Despite the absence of elevated levels of Th2 cytokines, apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented in vitro by antibodies to IL-10 or IL-4, two Th2 cytokines that downregulate Th1 cell responses, or by the addition of recombinant IL-12, a cytokine that upregulates Th1 functions. TCR-induced apoptosis of T cell hybridomas and preactivated T cells has been shown to involve the CD95 (Fas/Apo-1) molecule. CD4+ and CD8+ T cells from HIV-infected persons expressed high levels of the CD95 molecule, and, in contrast to T cells from controls, were highly sensitive to antibody-mediated CD95 ligation, which induced apoptosis in a percentage of T cells similar to that induced by TCR stimulation. As TCR-induced apoptosis, CD95-mediated apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented by the addition of recombinant IL-12. Together, these findings suggest that apoptosis of CD4+ T cells from HIV-infected persons involves an abnormal sensitivity to CD95 ligation, and to TCR stimulation in the presence of normal levels of Th2 cytokines. The preventive effect of IL-12 on both mechanisms has potential implications for the design of immunotherapy strategies aimed at the upregulation of CD4+ Th1 cell functions in AIDS.
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PMID:T helper type 1/T helper type 2 cytokines and T cell death: preventive effect of interleukin 12 on activation-induced and CD95 (FAS/APO-1)-mediated apoptosis of CD4+ T cells from human immunodeficiency virus-infected persons. 750 20

Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.
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PMID:Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. 750 78

The purpose of this investigation was to determine whether mouse lung fibroblast subsets have the ability to produce nitric oxide (NO), and if so, to characterize the induction and effects of its synthesis. Previously, we isolated Thy1+ and Thy1- subpopulations of mouse lung fibroblasts, which differ in terms of cytokine production, morphology, response to cytokines and radiation, and ability to present antigen to T lymphocytes. When treated with the proinflammatory cytokines IFN-gamma, TNF-alpha, and IL-1 alpha, these fibroblast lines produce micromolar quantities of NO2- and NO3-, two stable end products of the NO pathway. A combination of all three cytokines provided the greatest induction, and there was no measurable production of NO in unstimulated cells. Thy1+ fibroblasts have fewer requirements for induction of NO production than the Thy1- line, in that NO production could be induced by only two of the above cytokines, where the Thy1- fibroblasts required all three. Inducible NO synthase (iNOS) mRNA was shown to be present by the reverse transcriptase-polymerase chain reaction as early as 2 hr after cytokine treatment in both cell lines. Addition of the NO synthase inhibitors NG-monomethyl-L-arginine and aminoguanidine inhibited production of NO2- and NO3-, but not iNOS mRNA. This inhibition was partially reversed by the addition of an excess of L-arginine. Interestingly, inhibition of NO synthesis was shown to decrease IL-6 production by more than 50% in cytokine-treated Thy1+ fibroblasts. These results indicate for the first time that Thy1+ and Thy1- mouse lung fibroblast subsets have the capability to produce NO to differing extents in response to cytokines and may therefore play an important role in the inflammatory response in the lung as well as in the progression of lung disease.
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PMID:Induction of nitric oxide synthase in subsets of murine pulmonary fibroblasts: effect on fibroblast interleukin-6 production. 751 14

The expression of the cytokine genes was studied under physiological conditions in normal adult mice using RT-PCR method capable of detecting low levels of mRNA. Total RNA was prepared from brain, spinal cord, lung, spleen, liver and kidney of 6 to 8 week-old specific pathogen-free BALB/c mice by acid guanidinium thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by M-MLV reverse transcriptase, and amplified using the specific oligonucleotide primers for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, IFN-beta and IFN-gamma by PCR method. Although IL-1 mRNA was detected in all the organs, IL-3 mRNA was not detected in any organs tested. IL-2 or IL-4 mRNA and IL-5 mRNA were produced only in spleen and lung, respectively. However, IL-6, TNF-alpha and IFN mRNA were detected in some different organs. These results suggest that many kinds of cytokine mRNA were produced in vivo under physiological conditions in normal mice.
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PMID:[Expression of cytokine messenger RNA in mice in physiological conditions]. 751 36

The induction of the cytokine mRNA after infection with Herpes simplex virus (HSV) was studied using RT-PCR method capable of detecting low levels of mRNA. Total RNA was prepared from spleen lymphocytes 3 h after infection with HSV-1 (+GC virulent variant and -GCr attenuated variant of Miyama strain) by acid guanidinium thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by M-MLV reverse transcriptase, and amplified using the specific oligonucleotide primers for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, IFN-beta and IFN-gamma by PCR method. After HSV-1 infection, IFN-alpha, IFN-beta, IFN-gamma, IL-1 beta, IL-4, IL-6 and TNF-alpha mRNA were significantly induced, but IL-2, IL-3 and IL-5 mRNA were not induced. Although IFN-alpha, IFN-gamma and IL-6 mRNA were more strongly induced by infection with +GC virulent variant than -GCr attenuated variant, there was no significant difference in the expression of other cytokine mRNA between two variants. These results demonstrate that cytokine mRNA in addition to IFN was induced by HSV infection, and suggest that cytokines as well as IFNs may play a role in the defense mechanism against HSV infection.
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PMID:[Induction of messenger RNA of cytokines by Herpes simplex virus infection in mice]. 751 38


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