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)

Lymphoma was diagnosed in a 7-year-old domestic cat found to be infected with FeLV and feline immunodeficiency virus (FIV). The cat was affected by chronic disorders suggestive of immunosuppression, including gingivitis, periodontitis, keratitis, and abscesses. Despite treatment, peripheral keratitis of the left eye progressed, resulting in uveitis, chronic glaucoma, and eventual corneal rupture. Microscopic retinal and optic disk pathologic processes also were suspected. Abnormal jaw movements that were believed to be indicative of neurologic disease were observed. Approximately 17 months later, the cat developed generalized lymphadenopathy, hepatosplenomegaly, and bilateral renomegaly. Lymphoblastic lymphoma and glomerulonephritis were diagnosed histologically. Manganese- and magnesium-dependent reverse transcriptase activity were detected in supernatants from lymph node and spleen mononuclear cell cultures, suggesting T-lymphocyte infection with FeLV and FIV.
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PMID:Feline leukemia virus and feline immunodeficiency virus infections in a cat with lymphoma. 253 74

Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated autoimmune uveitis induced by immunization with bovine uveal melanin protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy. This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed for histology and the left eye was analysed for cytokines by quantitative reverse transcriptase-polymerase chain reaction. Western blot analysis showed that uveal melanin-protein contains gp100. In three independent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which received Ad2CMV-gp100 before immunization than in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injection prevents the development of EMIU, at least in part, through cytokine regulation.
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PMID:Recombinant adenovirus encoding gp100 modulates experimental melanin-protein induced uveitis (EMIU). 965 89

Ocular complication of AIDS are seen in about 75% of patients. Viral infections are predominant and can involve either external segment in the eye (Herpes type 8 in Kaposi sarcoma, molluscum contagiosum, Herpes simplex and zoster), or the posterior segment of the eye (CMV retinitis). The introduction of a Highly Active Antiretroviral Therapy (HAART) which associates two reverse transcriptase inhibitors and one antiprotease has changed the evolution of AIDS. The decrease of onset of CMV retinitis in AIDS patient is one of the best exemple. For the first time it was possible to stop the maintenance therapy against CMV retinitis in patients that have a sufficient increase in CD4+ cells and they did not present any relapse of CMV retinitis. But an increase of ocular inflammation can be observed with the onset of HAART such as uveitis or cystoid macular edema.
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PMID:[Diagnosis and treatment of ocular viral infections in AIDS patients]. 986 23

To identify the cellular immune processes underlying intra-ocular inflammation, aqueous humour was obtained at cataract surgery from 22 patients with clinically inactive uveitis and 24 patients with age-related cataract. mRNA expression for the cytokines IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta); T cell subsets CD3, CD4, CD8; monocytes and macrophages (CD14); and B cells (CD19) was measured using reverse transcriptase-polymerase chain reaction (RT-PCR) and radiometric analysis. The majority of uveitis patients demonstrated a T cell-mediated inflammatory response, predominately involving a Th1-like cytokine profile with expression of IL-2 and IFN-gamma in 16/22 and 18/22 samples, respectively. These cytokines were present in only a small number of patients with age-related cataract. This Th1-like polarization was supported by an increased expression of CD8 in a number of patients. IL-1beta was expressed in only six uveitic eyes. Only four patients expressed either IL-4 or IL-10 and no patient expressed both. TGF-beta mRNA could be detected in 18/22 uveitis patients and 15/24 controls. IL-12, the paradigmatic Th1-inducing cytokine, was absent in all samples but CD14 was expressed in the majority of patients and controls. CD19 could not be detected in any sample. The cellular infiltrate in the uveitic eyes showed clear evidence of low IL-1 and absent IL-12 expression despite a Th1-like profile and high expression of macrophages. This strongly suggests that the systemic immunosuppressive therapy used prior to surgery in some patients and/or the chronicity of the uveitis had actively suppressed/switched off macrophage function, leading to resolution of T cell activity.
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PMID:Molecular analysis of resolving immune responses in uveitis. 1046 47

Therapeutic and prophylactic regimens directed specifically against Mycobacterium avium complex (MAC) are increasingly being used in patients infected with the human immunodeficiency virus (HIV). Several of the drugs used in the management of MAC have been associated with significant drug interactions involving the cytochrome P450 (CYP) enzyme system. This enzyme system is also highly influenced by other drugs used in the management of patients with HIV, particularly the protease inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and azole antifungals. This article reviews the published concentrations or subtherapeutic concentrations of other drugs have been described. In particular, concurrent use of rifabutin with clarithromycin or fluconazole has resulted in increased concentrations of rifabutin and an accompanying increase in the incidence of rifabutin toxicities, including uveitis and leucopenia. Similar results have been seen when rifabutin is combined with protease inhibitors or delavirdine. The macrolides, clarithromycin and azithromycin, have also been associated with significant drug interactions. Clarithromycin has a higher affinity for CYP than azithromycin and, thus, is more frequently associated with clinically significant drug interactions. Clarithromycin is an inhibitor of CYP and may result in toxic concentrations of other drugs metabolised by this enzyme system. Such interactions have been described with rifabutin and the statin lipid-lowering agents. In addition, nevirapine and efavirenz have been shown to significantly reduce clarithromycin concentrations, whereas the protease inhibitors and delavirdine may increase clarithromycin concentrations. Other drugs used in the management of patients with MAC are not metabolised by CYP and thus have a lower incidence of interactions, although the absorption of ciprofloxacin may be impaired when it is given with products containing multivalent cations, such as didanosine. However, clinicians must remain vigilant for drug interactions when reviewing a patient's medication profile, keeping in mind both interactions that have been described in the literature and those that may be predicted based upon known pharmacokinetic profiles.
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PMID:Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. 1102 Jan 35

The purpose of this study was to determine the effects of an intravitreal device releasing cyclosporine A (CsA) on recurrent inflammatory episodes in experimental uveitis. Nine normal horses were immunized peripherally with H37RA-mTB antigen twice, and then received 25 microg of H37RA-mTB antigen intravitreally in the right eye and an equal volume of balanced salt solution intravitreally in the left eye. Two weeks later, the animals randomly received either a CsA or a polymer implant (without CsA) in both eyes 1 week following implantation of the devices, 25 microg of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammation were graded following injections and implantation. The animals from each group were euthanized at 3, 14, and 28 days following the second injection. Aqueous and vitreous humor protein concentrations were measured. The presence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells and amount of tissue destruction were determined. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed for equine specific interleukin (IL) 2 and 4, interferon-gamma (IFN gamma) and beta-actin. In addition, aqueous and vitreous humor and peripheral blood were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4h of the first intravitreal H37RA-mTB antigen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous flare, myosis, and vitreous opacity. The severity of signs peaked 48 to 72 h after injection and subsequently decreased back to normal within 14 days. Following the second injection, clinical signs in the eyes with the CsA device were less severe and significantly shorter in duration than signs with the polymer only implant eyes. Aqueous and vitreous humor protein levels, infiltrating cell numbers, total number of T-lymphocytes, and levels of IL-2 and IFN gamma-mRNA were significantly less in eyes with the CsA implant compared to eyes with the polymer only. CsA implants did not completely eliminate the development of a second ('recurrent') experimental inflammatory episode in these horses. However, the duration and severity of inflammation, cellular infiltration, tissue destruction, and pro-inflammatory cytokines RNA transcript levels were significantly less in those eyes implanted with the CsA device.
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PMID:Effect of an intravitreal cyclosporine implant on experimental uveitis in horses. 1104 57

Purpose: Acute retinal necrosis (ARN) is caused by varicella zoster virus (VZV) infection. In this study, we investigated the activity of this virus and expressions of some cytokines.Patients and Methods: The expressionof VZV thymidine kinase and some cytokines were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) in 9 eyes of 8 patients with ARN.Results: Thymidine kinase expression was observed in all samples except one. Several cytokines, such as interferon (IFN) gamma, tumor necrosis factor (TNF)alpha, interleukin (IL)-1 beta, IL-6, and transforming growth factor (TGF)beta 1 were observed in the samples. Among these cytokines, a statistically significant expression of IFNgamma was observed in the samples of ARN, when compared to those of proliferative vitreoretinopathy (PVR) or other uveitis. The expression of IFNgamma also decreased during successive follow-ups.Conclusion: These cytokines may play an important role in the immune response in ARN.
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PMID:Expression of the Varicella Zoster Virus Thymidine Kinase and Cytokines in Patients with Acute Retinal Necrosis Syndrome. 1109

We report the case of a 54-year-old HIV-seropositive man who was referred to us with unilateral uveitis. The patient had been taking triple antiretroviral therapy (three reverse transcriptase inhibitors) for one week when he presented with blurring of vision in the left eye. Two weeks later, active cytomegalovirus retinitis was suspected after fundus examination and ganciclovir was immediately administered. Even if the CD4 cell count was normal (423/microliter), the diagnosis was confirmed by the presence of CMV in the anterior chamber. This case shows that an elevated CD4 count is not incompatible with CMV retinitis, especially at the beginning of the antiretroviral therapy.
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PMID:[Cytomegalovirus retinitis despite normal CD4 levels in an HIV patient. Report of a case]. 1191 43

To evaluate the role of IFN-gamma (interferon gamma) in IL-12- (interleukin-12)-induced inhibition of the inflammatory response in the eye during endotoxin-induced uveitis (EIU). C57BL/6 wild type mice and IFN-gamma-deficient (GKO) mice were injected with 250 microg of Salmonella typhymurium endotoxin as a model for EIU. Animals were then injected intraocularly with 100 ng of rIL-12 or the equivalent volume of Phosphate-buffer saline (PBS). Histopathologic grading of disease was performed 12, 36 and 72 h after endotoxin injection. Chemokine mRNA expression in the eye was evaluated by reverse transcriptase-polymerase chain reaction. Depletion of NK1.1+ cells in vivo was performed using a PK136 antibody. Depletion of IFN-gamma was performed using the R4-6A2 antibody. C57BL/6 mice treated with rIL-12 intraocularly were protected from the development of EIU. Neutralization of IFN-gamma with a monoclonal antibody abrogated such protection. The IL-12 protective effects were lost in NK1.1-depleted mice. Intraocular IL-12 decreased the expression of keratinocyte-derived chemokines (KC) gene but had no effect on macrophage inflammatory protein (MIP-2) gene. The protective effect of IL-12 during EIU occurs through production of IFN-gamma by NK1.1+ cells. IL-12-induced higher levels of IFN-gamma are also correlated with lower expression of the chemokine KC, resulting in diminished attraction of neutrophils to the inflammatory site.
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PMID:NK1.1 cells downregulate murine endotoxin-induced uveitis following intraocular administration of interleukin-12. 1763 10

The human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) pandemic has pervasive effects on culture, economics, policy, and human development. All organs can be affected by complications of HIV/AIDS, including the eye. When sufficient resources are available and widespread antiretroviral resistance does not exist, the four available classes of antiretroviral agents - nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors - can be combined to provide highly active antiretroviral therapy (HAART). For many (not all) patients, HAART converts an inexorably fatal disease into a chronic disease with a fairly good prognosis. Use of HAART often induces partial immune recovery, which has predominantly beneficial effects on ocular complications of AIDS. However, HAART-induced immune recovery sometimes results in immune recovery inflammatory syndromes, such as immune recovery uveitis. Use of HAART is the single most useful intervention for most patients with ocular complications of AIDS. However, specific ocular therapy is also critical to avoid blindness in the early months before immune recovery can occur, or if HAART is unavailable. Increasing availability of HAART worldwide shows great promise to alleviate one of the world's greatest plagues. However, predictable secular trends in the AIDS epidemic make it likely that the number of cases of ocular complications of AIDS will increase substantially before they decrease. Ophthalmologists worldwide should be familiar with the diagnosis and management of cytomegalovirus retinitis - the most common ocular complication of AIDS - and should establish partnerships with physicians who are able to provide HAART. Research is needed to determine the optimal approach for managing cytomegalovirus retinitis in resource-constrained settings.
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PMID:Medical management of human immunodeficiency virus infection. 1871 Dec 66


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