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

Polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human T-cell lymphotropic virus types I [HTLV-I] and II [HTLV-II]) in multiple sclerosis. Eleven patients with relapsing-remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. Cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. Cultured cells were subjected to polymerase chain reaction analysis with primers selected for the pol and gag (human spumaretrovirus), pol and env (HTLV-I), and pol (HTLV-II) genes. Polymerase chain reaction was negative in all patient and blood donor control samples, whereas positive controls were consistently reactive with high sensitivity. No culture exhibited cytopathic effects and supernatants were negative for reverse transcriptase activity. Thus, our results do not support a role for these retroviruses in the pathogenesis of multiple sclerosis.
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PMID:No evidence for spumavirus or oncovirus infection in relapsing-remitting multiple sclerosis. 133 76

HTLV-1, HIV-1 and HIV-2 western blot analysis of sera from patients with multiple sclerosis (MS), from patients with other neurological diseases and from blood donors, revealed a rather frequent cross-reactivity with retroviral proteins in the MS group, though no patient was positive with the corresponding specific ELISA serology. Statistical analysis revealed a significant difference between the MS group and the two control groups for HIV-1 and HIV-2 reverse transcriptase fragments and for HTLV-1 p24. The general significance of these observations is discussed in the light of a retroviral hypothesis for the aetiology of MS. It is suggested that, if a retrovirus is present in MS patients, it does not necessarily belong to the HTLV sub-family and could as well be a lentivirus, like Visna virus, the causative agent of a demyelinating disease in sheep which is one--natural--model for MS.
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PMID:Antibody to reverse transcriptase of human retroviruses in multiple sclerosis. 172 34

Presence of cytopathic effect and enzyme reverse transcriptase in cultures of peripheral blood mononuclear cells is described in 2 of 15 patients with multiple sclerosis and none of healthy controls. These findings might indicate: the presence of a new human retrovirus in these individuals, despite the low detection rate, and the shortcomings inherent in methodology used for detection of known human retroviruses in the study of new groups of diseases, such as those with possible autoimmune background.
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PMID:Retrovirus in multiple sclerosis. 248 51

A leptomeningeal cell line (clonal but not immortal) was isolated from lumbar-punctured cerebrospinal fluid in a patient with definite multiple sclerosis (MS). This cell line, named LM7, was characterized by immunocytochemical and ultrastructural analyses and was found to produce specific viral reverse transcriptase activity, whereas electron microscopy revealed the presence of viral particles. This patient had no antibodies against human T-leukaemia virus type 1 (HTLV-I) or human immunodeficiency viruses types 1 and 2 (HIV-1, HIV-2). Moreover, monoclonal antibodies against HTLV-I and HIV-1 failed to recognize epitopes in induced LM7 cells. The possible relationship between MS and the virus present in LM7 cells is discussed.
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PMID:Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles. 248 22

Long-term peripheral blood mononuclear cell (MNC) cultures stimulated with interleukin 2 (IL-2) or IL-2 + phytohemagglutinin were established from 33 multiple sclerosis (MS) patients, 9 with other neurological diseases (OND), and 24 normal controls (C). Cultures were analysed for growth characteristics, reverse transcriptase (RT) in the culture medium, 2'-5' oligoadenylate synthetase in the cells, and cell morphology. None of these parameters differed in the MS group compared with the OND and C groups. Furthermore, 11 cerebrospinal fluid cell cultures were established without feeder cells. Morphology studies of the cells and RT assays of the supernatants from these cultures were normal. Induction studies by dexamethasone and 2-bromo-5'-deoxyuridine in 2 of these cultures did not reveal any signs of a virus. The significance of these results for the retrovirus hypothesis is discussed.
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PMID:Search for a retrovirus in long-term cultured cerebrospinal fluid cells and peripheral blood mononuclear cells from patients with multiple sclerosis. 261 88

Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Quervain's thyroiditis, multiple sclerosis, acquired hypogammaglobulinaemia, and certain forms of non-A, non-B hepatitis have come under passing suspicion of a retroviral aetiology. With AIDS threatening to become pandemic, and a second AIDS virus appearing in West Africa, human retroviruses are under intensive study for new antiviral drugs targeted to their unique mode of replication, and for the development of vaccines.
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PMID:Retroviruses and human disease. 288 52

Experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), is a paralytic disease of the central nervous system (CNS) mediated by T-lymphocytes reactive to myelin basic protein (MBP). Lewis rats actively immunized with fragment 68 to 82 of guinea pig MBP develop a monophasic disease with spontaneous recovery. Lymphocyte recognition of the primary encephalitogenic sequence of MBP (fragment 68 to 82) is V beta 8.2 T cell receptor (TCR) skewed [1-3]. Lewis rats in clinical remission at 1 month and 3 months after spontaneous resolution of EAE retain V beta 8.2 T-lymphocytes in the CNS when analyzed by reverse transcriptase polymerase chain reaction or in situ hybridization. In contrast, 1 and 3 months after clinical remission from syngeneic bone marrow transplantation, V beta 8.2 T lymphocytes are absent from the CNS. During clinically active EAE and inflammatory breakdown of the blood-brain barrier, immune ablation and reconstitution with syngeneic bone marrow results in clinical tolerance of the new immune system to myelin.
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PMID:Syngeneic bone marrow transplantation eliminates V beta 8.2 T lymphocytes from the spinal cord of Lewis rats with experimental allergic encephalomyelitis. 747 84

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

Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences. In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B7-1 results in T cell-mediated autoimmune disease, whereas B7-2 stimulation generates regulatory autoreactive T cells that abrogate disease severity. Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry. In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression of B7-1 and interleukin (IL) 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B7-1 staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B7-2 was expressed predominantly on macrophages both in MS lesions of varied time duration and in inflammatory infarcts. These findings indicate that an early event in the initiation of MS involves upregulation of B7-1 and IL-12, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses.
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PMID:Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. 750 44

We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a female patient with nervous system disease, the biological characteristics of CM-1 cells was studied in this paper. Another T lymphocytes, such as peripheral T lymphocytes donated by a male patient with multiple sclerosis, could be transformed into a malignant lymphoma line by using filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line was established. The CM-1 and CM-2 cells were transplanted by subcutaneous inoculation into nude mice, and could cause the occurrence of typical malignant lymphoma. The observation of electron micrographs suggested the existence of virions in the CM-1 and CM-2 cells, and these virions were similar to retrovirus in the ultra-structure characteristics. It was found that this virus possesses reverse transcriptase activity. Results obtained from serological assay, molecular hybridization and PCR excluded the existence of other human viruses, which were commonly used in our laboratory. The unknown virus possesses strong transformation activity, and probably is a new retrovirus. Meanwhile, the work on the clone and sequence analysis of this virus are being carried out.
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PMID:Establishment of a human malignant T lymphoma cell line carrying retrovirus-like particles with RT activity. 751 81


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