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

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to further evaluate the relative safety of extracorporeal photopheresis in the treatment of patients with AIDS-related complex. Twenty patients with AIDS-related complex, three from the initial report and 17 additional patients, were enrolled. The patient population had various risk factors. There were nine homosexuals, five heterosexual consorts of human immunodeficiency virus (HIV)-positive patients, four reformed i.v. drug abusers, and two hemophilia patients. The patients received monthly treatment with extracorporeal photopheresis. In 16 of the 19 patients, this study provides evidence of clinical stability over a longer period. The relative stability of beta 2-microglobulin and neopterin levels demonstrates that photopheresis therapy does not have an untoward effect on the degree of activation of the immune system with respect to induction of HIV replication. Antibody titers to the major viral antigens, envelope glycoproteins (gp) 120 and 41, reverse transcriptase enzyme gp 66/31 and 55, and the core protein p24 remained stable throughout the course of therapy. A subjective improvement was noted in the majority of patients. The evaluation of T-cell subsets revealed that the photopheresis treatment did not have a detrimental effect on CD3 and CD8 cells. Some decreases were noted in the CD4 cell counts but the decline may be less than is normally seen at corresponding stages of HIV infection. Skin test responsivity improved in 11 patients, remained unchanged in seven patients, and declined in two. The preliminary results suggest that in HIV disease, extracorporeal photopheresis is safe and warrants a prospective controlled trial.
...
PMID:Extracorporeal photopheresis in the treatment of AIDS-related complex: extended trial. 809 83

Since 1987 major advances have been made in our understanding of the pathogenesis of infection and the possible inhibition of the HIV virus. Various drugs targeted to the different steps of viral replication have been selected, but drugs such as soluble CD4 or dextran derivatives aimed to inhibit or interfere with the GP120-CD4 attachment step have shown little or no clinical benefit. Protease inhibitors or interferons acting at the post-transcriptional level are currently under phase I to II investigation. The only group of compounds clinically active belong to the nucleosides analogues that act as DNA chain terminators and by inhibiting viral reverse transcriptase. Zidovudine (AZT), didanosine (ddI) and dideoxycytidine (ddC) have been extensively studied, and used on a large clinical scale. Stavudine (D4T), deoxyfluorothymidine (FLT) and 3'thiacytidine (3TC) are entering phase I-II studies. Being the first nucleoside analogue discovered and used since early 1985, zidovudine remains the gold standard of anti-HIV therapy. Zidovudine is indicated at a dosage varying between 500 and 1000 mg in patients with AIDS and ARC, in asymptomatic patients with CD4 < 200/mm3 and in asymptomatic patients with CD4 between 200 and 500 cells/mm3 with a rapid decrease of CD4 cell count or a positive P24 circulating antigen. There is as yet no consensus concerning patients with more than 500 cell/mm3. ddI and ddC are currently indicated for patients intolerant to AZT or in those who have not responded (clinically or biologically) to AZT. Emergence of resistance to AZT has been reported in 30 to 80% of patients at various stages of the disease and after six to nine months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Current use of anti-HIV drugs in AIDS. 840 95

Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable.
...
PMID:Zidovudine toxicity. Clinical features and management. 848 Dec 17

Before becoming acyclic, middle-aged rats display an attenuated LH surge and a decreased number of activated GnRH neurons. The present study examined whether the decreased activation of GnRH neurons in middle-aged rats could be due to defective glutamate neurosignaling in the hypothalamus. Arcuate nucleus/median eminence (ARC/ME) fragments were isolated from young (2-month-old) and middle-aged (9- to 11-month-old) rats at 1700 h on proestrus and incubated in vitro with or without the specific glutamate agonists, D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (1 mM), kainate (1 mM), and N-methyl-D-aspartate (NMDA; 50 mM). The results showed that basal GnRH release was similar in the two age groups. In contrast, stimulated GnRH release by D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and NMDA was significantly attenuated in middle-aged vs. young rats. KCl stimulation at the end of the experiments confirmed the viability of all ARC/ME fragments. Quantitative reverse transcriptase-PCR revealed that messenger RNA levels for the major NMDA receptor subunit (NMDAR1) were significantly lower in the preoptic area and ARC/ME of the middle-aged rat on proestrus afternoon. As a whole, these findings suggest that a defect in hypothalamic glutamate neurosignaling may be an important mechanism leading to age-related defects in LH secretion and acyclicity in female animals.
...
PMID:Decreased gonadotropin-releasing hormone neurosecretory response to glutamate agonists in middle-aged female rats on proestrus afternoon: a possible role in reproductive aging? 864 Nov 83

Serum samples of four HIV-1 seroconversion serum panels were subjected in a single assay tube simultaneously to ultrasensitive enzyme immunoassays (immune complex transfer enzyme immunoassays) for p24 antigen of HIV-1 and for antibody IgGs to p17 and reverse transcriptase (RT) of HIV-1. Signals became positive 7-15 days earlier than the detection of antibodies to HIV-1 by conventional methods and remained strongly positive even after levels of p24 antigen declined. Thus the simultaneous detection of p24 antigen and antibody IgGs to p17 and RT made possible both as early a diagnosis of HIV-1 infection as the appearance of p24 antigen in the circulation, shortening "the window period," and as reliable a diagnosis of the infection as that by the detection of antibodies to HIV-1 from the time of seroconversion until late stages of the infection, since the serum level of antibody IgG to RT was high not only in asymptomatic carriers but also in patients with AIDS-related complex and AIDS.
...
PMID:Earlier diagnosis of HIV-1 infection by simultaneous detection of p24 antigen and antibody IgGs to p17 and reverse transcriptase in serum with enzyme immunoassay. 881 65

T-cell mediated cytotoxicity play an important role in the control of human immunodeficiency virus (HIV) infection. The polyclonal cytotoxic T lymphocyte (CTL) response against target cells infected with a recombinant vaccinia virus expressing Env, Gag, Nef or reverse transcriptase (RT) proteins has been studied in four groups of individuals: acquired immune deficiency syndrome (AIDS) patients, AIDS-related complex (ARC) patients, HIV-1 seropositive subjects and seronegative controls. CTL lines have been generated by non-specific stimulation with phytohemagglutinin and interleukin-2 and target cells have been prepared from autologous B lymphocytes. CTL from asymptomatic and ARC individuals recognized most of the various proteins of HIV-1 but those from AIDS patients had very low or absent responses to the majority of proteins, with the anti-Nef cytotoxic activity decreasing first. Two of 10 AIDS patients had demonstrable recognition of Gag p24, one of RT and eight patients had no recognition of any of the proteins. The effector cells were demonstrated to be predominantly of the CD8+ phenotype, using the appropriate monoclonal antibodies. When heterologous target cells were substituted for autologous cells, the cytotoxic response was abrogated in the vast majority of cases demonstrating its human leucocyte antigen (HLA) class I restriction. Among the 10 HIV-seronegative subjects, nine had no CTL activity against the various HIV-1 proteins but one subject was able to recognize Env and RT. In the evolution of HIV infection from the seropositive stage to AIDS, CTL polyclonal activities progressively decrease, with Nef responses disappearing first, then Env and Gag p55, followed by RT and Gag p24.
...
PMID:Loss of T-cell cytotoxic responses in the course of HIV-1 infection. 949 84

Antibodies inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcriptase activity (RTI-antibody), Binding inhibition antibody (BI-antibody) and polymerization inhibition antibody (PI-antibody) were investigated for their ability to inhibiting RT activity in 248 HIV-1 infected individuals and 99 healthy individuals. In BI-antibody, high titer samples were determined more in than in RTI- and PI-antibodies. No significance was indicated between AC, ARC and AIDS is any antibody, however, progression from AC to AIDS was poled to high titer and low titer in RTI- and BI-antibodies. Moreover, time course of each antibody levels in the same infected individuals were resulted in no change, going up or down through all the experimental term, though all samples were collected in AC. These results were suggested that the determination factor of each stage in HIV progression would be multiple, and that the various dynamics of RTI-, BI- and PI-antibodies in the same infected individuals might be caused in the term from HIV infection to AIDS progression, prognosis or appearing of the drug resistant strain but stages of the disease.
...
PMID:[Studies for dynamics of reverse transcriptase inhibiting antibody in sera from HIV-1 infected individuals]. 974 18

The alpha2-adrenoceptor mediating inhibition of forskolin-stimulated cyclic AMP accumulation in human neuroblastoma SH-SY5Y cells was further characterized. The alpha2-adrenoceptor agonists, UK 14,304 (5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline), oxymetazoline, guanfacine, (-)-noradrenaline and clonidine concentration-dependently decreased cyclic AMP accumulation in this cell line (Emax ca. 50% inhibition). Agonist pEC50 values ranged between 6.7 and 7.8. Clonidine was a partial agonist. The effects of UK 14,304 were blocked after a pertussis toxin treatment. The concentration-response curves of UK 14,304 were shifted to the right in a parallel manner by the following antagonists (mean pK(B) values): yohimbine (8.17), idazoxan (7.63), prazosin (6.66), 2-[2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2 H,4H) isoquinolindione (ARC 239; 7.12) and 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB-4101; 8.12). The relatively high pKB values of prazosin and ARC 239 point to a non-alpha2A-adrenoceptor-mediated effect. The relatively high pK(B) value of WB-4101 further characterizes the alpha2-adrenoceptor in SH-SY5Y cells as being of the alpha2C subtype. The analysis of the expression of alpha2-adrenoceptor subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the exclusive presence of alpha2C-adrenoceptor mRNA in SH-SY5Y cells. We propose that inhibition of forskolin-stimulated cAMP accumulation in SH-SY5Y cells be used as a functional model of human, native alpha2C-adrenoceptors.
...
PMID:Functional alpha2C-adrenoceptors in human neuroblastoma SH-SY5Y cells. 1037 21

The unique nature of the replication cycle of the retroviruses, including HIV, offera number of possible targets for chemotherapeutic agents. These are RNA viruses which have the capacity to make DNA copies through their characteristic enzyme, reverse transcriptase, encoded in the pole region of the viral genoma. Reverse transcription is an attractive target for therapeutic intervention as this event is uniquelly associated with retroviruses. Dideoxynucleoside analogues can compete with endogenous nucleosides that are the natural substrate for reverse transcriptase or may be incorporated intro the growing chain of proviral DNA and terminate elongation. Reverse transcriptase inhibition is the principal mechanism of action of zidovudine (AZT) and related nucleosides, dideoxyinosine (ddl) and dideoxycitidine (ddC), which all attach to reverse transcriptase to the same site. This review will discuss current approaches to the antiretroviral therapy in AIDS patients. Several well controlled clinical trials have established both the efficacy and toxicity of AZT in patients with AIDS and severe ARC and it was shown that this drug decreased the incidence and severity of opportunistic infections, with the highly significant reduction in early mortality. The efficacy of newer reverse transcriptase-inhibiting nucleoside derivatives will be discussed too, as well as the issue of combination therapies.
...
PMID:[Antiretroviral therapy of acquired immunodeficiency syndrome (AIDS)]. 1817 Sep 76

Sequencing analysis of a 5-kb DNA fragment from Streptomyces venezuelae ATCC 15439 revealed the presence of one 3.1-kb open reading frame (ORF), designated afsRsv. The deduced product of afsR-sv (1,056 aa) was found to have high homology with the global regulatory protein AfsR. Homology-based analysis showed that afsR-sv represents a transcriptional activator belonging to the Streptomyces antibiotic regulatory protein (SARP) family that includes an Nterminal SARP domain containing a bacterial transcriptional activation domain (BTAD), an NB-ARC domain, and a Cterminal tetratricopeptide repeat domain. Gene expression analysis by reverse transcriptase PCR (RT-PCR) demonstrated the activation of transcription of genes belonging to pikromycin production, when afsR-sv was overexpressed in S. venezuelae. Heterologous expression of the afsR-sv in different Streptomyces strains resulted in increased production of the respective antibiotics, suggesting that afsR-sv is a positive regulator of antibiotics biosynthesis.
...
PMID:Identification and functional characterization of an afsR homolog regulatory gene from Streptomyces venezuelae ATCC 15439. 1930 59


<< Previous 1 2 3 4 5 6 Next >>

---