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)

Helper T cell cytokine and antibody responses were investigated in mice after infection with Babesia microti (King strain). Infection of CBA mice with 106 parasitized erythrocytes resulted in the development of a transitory high parasitaemia which peaked 14 days post infection (DPI), and was resolved at 24 DPI. Th1 responses were activated predominately during the acute phase (6-18 DPI) whereas Th2 responses predominated during the recovery phase (14-28 DPI) as detected by the reverse transcriptase polymerase chain reaction. Increased expression of Th1 cytokines was first detected at 6 DPI (IL-2) and 8 DPI (IFN-gamma) and their peak levels were reached at 12 DPI. After the peak levels were reached, they progressively declined and fell to baseline levels (22 DPI). Increased expression of Th2 cytokines (IL-4 and IL-10) first appeared at 14 DPI, peaked at 20 DPI and Th2 cytokine levels were elevated till the end of the study (28 DPI). Levels of serum IFN-gamma detected by a sandwich ELISA correlated well with IFN-gamma gene expression and were detectable at 8-18 DPI. IgM against B. microti was first detected in serum by ELISA at 4 DPI, and peaked at 10 DPI. The levels of IgM subsequently declined but remained positive at low titre till the end of study. IgG against B. microti was first detected at 8 DPI and peak levels were reached at 24 DPI and remained at that level until the end of study. The results of the present study show that Th1 cytokines predominated in the early inflammatory response and might be involved in control of levels of acute parasitaemia whereas the Th2-associated responses, including expression of IL-4 and IL-10 and the production of parasite-specific IgG, might be the functional means for the reduction and clearance of the parasite from the body. It was concluded that an effective vaccine against Babesia spp. should be designed to induce Th1 responses to maintain the parasitaemia at unfulminating levels and also maintain Th2 responses to clear the parasite from the body.
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PMID:Helper T cell and antibody responses to infection of CBA mice with Babesia microti. 1065 20

Hepatitis A is a widespread infectious disease world-wide. In Italy, shellfish consumption was shown to be a major risk factor for hepatitis A infection, especially when these products are eaten raw or slightly cooked. The aim of the present study was to evaluate Hepatitis A virus (HAV) resistance in experimentally contaminated mussels treated at different temperatures (60, 80 and 100 degrees C) for various times. The presence of HAV was evaluated by cell culture infection and reverse transcriptase-polymerase chain reaction confirmation. The experiments, carried out on HAV suspension and contaminated mussel homogenate both containing about 10(5) 50% tissue culture infectious dose ml-1, showed that, under our experimental conditions, the treatments at 60 degrees C for 30 min, 80 degrees C for 10 min and an immersion at 100 degrees C for 1 min were not sufficient to inactivate all the viruses; it was necessary to prolong the treatment at 100 degrees C for 2 min to completely inactivate the virus. Thus it is advisable to eat only cooked shellfish, paying particular attention to the times and temperatures used in the cooking process, since evidence suggests that the shellfish body may protect the virus from the heat effect.
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PMID:Inactivation of hepatitis A virus in heat-treated mussels. 1066 11

Anti-HIV drug regimens can fail for a number of reasons including virological resistance, difficulties of adherence and poor tolerability. However, this brief review focuses on the development of "pharmacological" resistance as an area of great importance in drug failure. For nucleoside reverse transcriptase inhibitors (NRTIs) this is related to the possible down-regulation of the intracellular phosphorylation of an NRTI with time. For protease inhibitors the concern is cells expressing transmembrane energy-dependent transporters (such as p-glycoprotein, p-gp; or multi-drug resistance protein, MRP) which efflux drug (particularly protease inhibitors) out of the cell so that intracellular concentrations of drug are insufficient for antiviral effect.
Infection 1999
PMID:Pharmacological issues relating to viral resistance. 1088 28

Several first-generation nucleoside analogues have been tested against chronic hepatitis B virus (HBV) infection, but trials were unsuccessful or accompanied by toxicity. Recently, oral second-generation nucleoside analogues have been developed that have potent activity against HBV. The best-studied compound so far is lamivudine ((-)2'-deoxy-3'-thiacytidine; 3TC). Lamivudine is an inhibitor of reverse transcriptase (RT) activity and is in clinical use in human immunodeficiency virus (HIV)-infected individuals. As several studies on the use of lamivudine for hepatitis B show, the development of resistance in the viral polymerase under lamivudine treatment, however, causes a significant clinical problem. All other drugs in advanced clinical development for HBV are nucleosides; cross-resistance is therefore expected in most cases. The history of HIV treatment demonstrates that new classes of drugs, the protease inhibitors and non-nucleosidic inhibitors of RT, allowed for a longer-term clinical benefit when used in combination with nucleoside analogues. The development of non-nucleosidic compounds with different modes of action therefore appears very important for the treatment of chronic hepatitis B as well.
Infection 1999
PMID:Development of resistance and perspectives for future therapies against hepatitis B infections: lessons to be learned from HIV. 1088 29

The utilization of accurate and sensitive methods for the measurement of cytokines in body fluids is prerequisite for the proper use of these mediators in clinical practice. Many factors contribute to the complexity of cytokine quantitation. Bioassays historically preceded immunoassays, which are now very popular, but there is a need for standardization. Nevertheless, due to the local effects of cytokines, the study of their blood levels is of limited value for an understanding of the pathophysiology of these mediators. This explains the development of alternative approaches to assess the ability of cells to produce cytokines. These include the Enzyme-Linked Immuno Spot Assay (ELISPOT), the measurement of cell-associated cytokines by flow cytometry, and the study of cytokine secretion by isolated peripheral blood mononuclear cells or by whole blood test. All these techniques, associated with a local detection of cytokines by immunohistochemistry or in situ hybridization and reverse transcriptase polymerase chain reaction, appear to be complementary tools for a better understanding of the biology of cytokines. Selected examples of possible clinical applications related to infectious diseases, cancer, autoimmune diseases, allergy, transplantation and preclinical evaluation of drugs and biotechnology products are given.
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PMID:The clinical usefulness of the measurement of cytokines. 1092 46

Antiretrovirals, particularly nucleoside analogue reverse transcriptase inhibitors (RTIs) - DDI, 3TC and D4T, are widely used to effectively control human immunodeficiency virus (HIV) infection. These drugs have several adverse effects including anemia, peripheral neuropathy, pancreatitis and, on rare occasions, lactic acidosis. We describe the case of a 39 year old patient who had severe lactic acidosis after receiving stavudine (D4T) and didanosine (DDI) for an 8 month period. She had never manifested an opportunistic infection and presented a CD4 count of 378 cells/mm3 and an undetectable viral load (< 400 copies/ml). The purpose of the following report is to alert clinicians and infectious diseases specialists to the occurrence of lactic acidosis in asymptomatic HIV patients receiving antiretrovirals for long periods of time.
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PMID:Lactic acidosis and antiretroviral therapy: a case report and literature review. 1093 99

Infection of peripheral blood mononuclear cells (PBMNCs) has been demonstrated to be a crucial event in the vertical transmission of viruses, and it is known that hepatitis C virus (HCV) can infect PBMNCs. The relationship between vertical transmission of HCV and the presence of positive and negative strands of HCV-RNA in the PBMNCs of HCV-carrier mothers was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR). During the study, 13 consecutive mothers who transmitted infection to their offspring and 53 consecutive mothers who did not were examined. The positive strand of HCV-RNA was identified in the PBMNCs of all mothers who transmitted the infection and in 13 of 53 mothers who did not (P < 10(-6)). The HCV-RNA(-) strand was found in 5 of 13 mothers who transmitted the infection, and the strand was not found in the mothers who did not transmit the infection (P =.0001). Neither maternal PBMNC infection nor HCV transmission to the offspring was significantly related to the viral genotype or to the maternal viral load. These data show that maternal PBMNC infection by HCV and viral replicative activity in PBMNCs are important factors in the transmission of HCV from mother to child. The mechanism through which HCV infection of PBMNC favors vertical transmission of the virus is still incompletely understood.
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PMID:Vertical transmission of HCV is related to maternal peripheral blood mononuclear cell infection. 1097 45

The aim of the study presented here was to describe the clinical presentation and outcome of invasive pulmonary aspergillosis (IPA) in a cohort of HIV-infected patients and to assess factors associated with survival by means of a longitudinal study of all HIV-infected adults with IPA who attended the infectious diseases service of a tertiary center between January 1985 and December 1998. The outcome measure was the time to death after diagnosis of IPA. The endpoint for data collection and survival analysis was 31 December 1998. Nineteen of 1,605 HIV-infected patients were identified, resulting in an overall IPA attack rate of 1.12%. Most patients had AIDS (95%). Unilateral cavitary disease was the most frequent radiographic presentation (37%). Median survival was 148 days (95% confidence interval [95% CI], 0-402), but it exceeded 12 months in 37%. In patients in whom antiretroviral treatment (ART) was initiated or modified in relation to the IPA diagnosis, median survival increased to 906 days (95% CI, 754-1,058; 1-year survival, 83%) compared with 86 days in those who did not take any ART (95% CI, 55-117; 1-year survival, 8%; P=0.0002). Survival was even longer when ART changes included only nucleoside reverse transcriptase inhibitors, prior to the availability of protease inhibitors (833 days, 95% CI, 369-1,297; 1-year survival 75%; P=0.003). Three (16%) patients are still alive after a mean time of 36 months postdiagnosis. Although IPA is a life-threatening complication of advanced AIDS, it does not always lead to short-term death. An adequate management of HIV infection together with antifungal treatment may prolong survival and, as described for other AIDS-related disorders, a significant decrease in its occurrence can be expected.
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PMID:Role of antiretroviral therapy in long-term survival of patients with AIDS-related pulmonary aspergillosis. 1105 2

Infection of mouse trigeminal ganglia by herpes simplex virus induces cytokine expression that persists long after infectious virus or viral antigens become undetectable. To examine mechanisms underlying this phenomenon, we used a thymidine kinase mutant, dlsptk, which fails to replicate in ganglia and does not reactivate upon ganglionic explant. Using quantitative reverse transcriptase-polymerase chain reaction assays, we found that levels of interferon-gamma and tumor necrosis factor-alpha transcripts in dlsptk-infected ganglia were lower than those in wild type-infected ganglia, but were significantly (eight- to 10-fold) higher than those in mock-infected ganglia from Day 3 to Day 100 postinfection. We also studied latency-associated transcript (LAT) negative mutants that exhibit increased expression of productive cycle transcripts in ganglia. Ganglia infected with these mutants contained levels of cytokine transcripts similar to those in wild type-infected ganglia; any increases in viral antigen expression mediated by the LAT deletion were not accompanied by increased cytokine expression. Thus, neither viral replication, the ability to reactivate, nor LAT expression in ganglia is required for persistent elevated cytokine expression. The results provide indirect evidence that low-level expression of viral productive cycle genes in neurons can provide signals that elicit cytokine expression.
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PMID:Persistent elevated expression of cytokine transcripts in ganglia latently infected with herpes simplex virus in the absence of ganglionic replication or reactivation. 1111 95

Microbial infection can impact on the course of autoimmune disease, both in disease-inducing and disease-protecting capacities. Here we investigated if infection with Trypanosoma brucei brucei (Tbb), the protozoan causative agent of African Sleeping Sickness, could ameliorate the course of CIA in the Dark Agouti rat, an experimental model which shares many features with human rheumatoid arthritis. Infection of animals with living, but not inoculation with dead Tbb resulted in complete or significant reduction of clinical arthritic symptoms. Infection prior to collagen immunization was more effective than a later treatment, and this effect was related to the level of parasitaemia. Using reverse transcriptase-polymerase chain reaction we detected an increase in interferon-gamma mRNA in the draining lymph nodes of Tbb-treated animals relative to controls at day 28 after disease induction. Transforming growth factor-beta could be detected in the lymph nodes in four out of six animals that had received Tbb. In the joints, immunohistochemistry revealed reduced production of tumour necrosis factor-alpha in Tbb-treated animals relative to controls. The most striking difference between Tbb-infected and control groups, as measured by ELISA, was the down-regulation of anti-collagen II IgG antibody responses in parasite-infected animals. We conclude that live parasites can exert an immunomodulatory and protective effect in CIA in which several mechanisms may work in parallel, although the almost complete down-regulation of the anti-collagen antibody response may alone explain the protective effect in CIA. The described model may be useful in further attempts to use the mechanisms involved in parasite immune defence to prevent and treat certain autoimmune conditions.
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PMID:Parasite-mediated down-regulation of collagen-induced arthritis (CIA) in DA rats. 1112 58


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