Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increase in levels of estrogen and progesterone during pregnancy may affect intra-uterine HIV-1 infection through their effect on maternal immunocompetent cells. These hormones were examined for containing HIV-1 production from ACH-2 lymphocytes and U1 monocytes. Neither of the hormones has an effect on ACH-2, but with U1, the physiological concentrations (0.1 microgram 0.1 ng) of progesterone and estrogen demonstrate significant inhibition of HIV-1 release. Except for the highest dose of 1 microgram/ml, the dose-response to progesterone and estrogen was not correlated with the negative influence on proliferation of both types of cells. The results suggest that in vivo low doses of female steroids may display specific antiviral activity in monocytes but not in lymphocytes.
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PMID:Pregnancy hormones, estrogen and progesterone, prevent HIV-1 synthesis in monocytes but not in lymphocytes. 160 Nov 28

HIV infection is associated with a long period of clinical latency before the development of symptoms and HIV-related disease. Two chronically HIV-infected cell lines, U1 (promonocytic) and ACH-2 (T-lymphocytic) have been developed as models for studying the mechanisms governing viral latency and the reactivation of virus expression. We have previously shown that a variety of physiologic stimuli, including cytokines and cell stress, can up-regulate HIV expression from these cell lines. In this study we demonstrate that heat shock can also up-regulate the production of virus from both ACH-2 and U1 cells. Heat induction of virus appears to be mediated at the transcriptional level as established in long terminal repeat-chloramphenicol acetyl transferase transient transfection experiments with the use of U937 cells. This inductive effect in part requires the NF-kappa B-binding region of the HIV-long terminal repeat. Furthermore, although physiologic levels of heat are not sufficient to directly induce virus production from these cells, these temperatures are able to synergistically enhance virus production in U1 cells stimulated with IL-6 and granulocyte macrophage-CSF. In contrast, the inductive effect of other cytokines (i.e., TNF-alpha) was not affected by heat stimulation. These in vitro observations suggest that the hyperthermia associated with opportunistic infections, particularly in conjunction with certain cytokines that are released during immune reactions, may play a role in the in vivo induction of HIV expression in infected cells.
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PMID:Heat shock induction of HIV production from chronically infected promonocytic and T cell lines. 169 94

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.
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PMID:Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage. 170 78

Alpha interferon (IFN-alpha) is effective in preventing the release of human immunodeficiency virus (HIV) from chronically infected T-lymphocytic (ACH-2) and promonocytic (U1) cell lines stimulated with the phorbol ester phorbol-12-myristate-13 acetate (PMA). In the present study, we observed that together with particle production, shedding of HIV antigen (p24gag) occurs in the T-cell line ACH-2 both constitutively and after stimulation with PMA. IFN-alpha, although effective in suppressing the release of HIV particles, did not inhibit shedding of p24gag into the culture supernatants of either unstimulated or PMA-stimulated cells. These observations may be of relevance in the evaluation of the in vivo efficacy of IFN-alpha treatment of HIV-infected individuals as determined by levels of p24 antigen in plasma.
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PMID:Alpha interferon suppresses virion but not soluble human immunodeficiency virus antigen production in chronically infected T-lymphocytic cells. 171 Feb 93

Viral replication seric markers (VRSM), (BeHAg, BcHAg, and DNA-VHB) and the hepatic tissue BcHAg of thirty four patients suffering from chronic hepatopathies (6 PCH, 18 ACH, and 10 cirrhosis) were investigated. The greatest incidence of RVSM was observed in PCH. The combined study using all the markers demonstrated a positive correlation: DNA-VHB and BeHAg (p less than 0,001); DNA-VHB and BcHAg (p less than 0,001); BeHAg and BcHAg (p less than 0,001). The same result was obtained when comparing BcHAg (n) with the rest of RVSM: DNA-VHB (p less than 0,001), BeHAg (p less than 0,001) and seric BcHAg (p less than 0,01). Patients with a most intense histologic activity according to the Knodell index, presented a higher ratio of positive nuclei for BcHAg. The conclusion is that there is a good correlation amongst replication markers, specially hepatic BcHAg and DNA-VHB.
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PMID:[Study of viral replication in HbsAg positive chronic hepatitis]. 178 40

The effects of electrical field stimulation and of purine compounds, adenosine and adenosine-5'-triphosphate (ATP) were examined on the mouse isolated rectum. Electrical field stimulation induced frequency-dependent contractions of mouse rectal muscles which were potentiated by physostigmine and inhibited by atropine or tetrodotoxin. Contractile amplitude at 37 degrees C was significantly (P less than 0.05) greater than at 25 degrees C, but the degree of potentiation by physostigmine was significantly (P less than 0.05) greater at 25 degrees C. ATP (1.6 x 10(-4)-1.28 x 10(-3) M) and adenosine (1.8 x 10(-4)-1.48 x 10(-3) M) inhibited in concentration-related fashion contractile responses induced by KCl (1.34 x 10(-2) M-1.07 x 10(-1) M) by acetylcholine (2.2 x 10(-7) M-1.4 x 10(-5) M) and by CaCl2 in high KCl (120 mM)-CaCl2-free Tyrode solution. Theophylline and quinidine ('purinoceptor' antagonists) antagonized ACH contractile effects and so could not be satisfactorily employed in the characterization of the purine receptors in the mouse rectum. It may be concluded from this study that in the mouse rectum, acetylcholine is an excitatory neurotransmitter and that there is a non-adrenergic, non-cholinergic inhibitory neuromuscular transmission in this tissue. Further, ATP and adenosine have been demonstrated to cause relaxation in this tissue by possibly a post-synaptic mechanism involving inhibition of Ca2+ influx into the depolarized muscle.
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PMID:The effects of electrical stimulation, adenosine and adenosine-5'-triphosphate (ATP) on mouse rectal muscle. 187 77

The effects of oxygen deprivation, or anoxia, on human immunodeficiency virus (HIV-1) expression in chronically (ACH.2) and acutely (H9/HIV-1-IIIB) infected cell lines was investigated. Temporary cellular anoxia has previously been shown to activate transcription of endogenous type C leukemia virus sequences, resulting in a significant increase in retroviral RNA within the cell (1). Here we report a 15-fold increase in HIV-1-specific RNA in unstimulated ACH.2 T cells within 24 h of anoxia. This induction of RNA is accompanied by an accumulation of intracellular p24 gag protein as well as an increase in envelope protein. Anoxia induces a further increase in total HIV-1 RNA in ACH.2 cells prestimulated to produce virus by phorbol 12-myristate 13-acetate and in H9 T cells acutely infected with HIV-1-IIIB. The induction of RNA in ACH.2 cells appears to be reversible. Anoxic culture for 24 h followed by a 24-h re-oxygenation period results in a return to "resting state" levels of HIV-1 RNA. These data indicate that oxygen tension within the cellular environment modulates HIV-1 expression, providing a model system in which to study the reversible regulation of HIV-1 RNA and viral gene products within the cell.
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PMID:Anoxia induces human immunodeficiency virus expression in infected T cell lines. 190 63

The effect of recombinant protein from the envelope (gp120) of the HIV on B lymphocytes purified from either HIV-infected individuals or healthy seronegative controls was examined. B cells from peripheral blood and lymph nodes of HIV-infected individuals spontaneously secreted TNF-alpha; this secretion was augmented by the presence of gp120, whereas B cells from healthy seronegative donors failed to secrete significant levels of TNF-alpha in the presence or absence of gp120. In a coculture system of B cells and chronically HIV-infected T cells (ACH-2), where viral expression is largely mediated by TNF-alpha, gp120 increased virus expression only if the B cells were obtained from HIV-infected individuals. The effects of gp120 on viral expression in this system were not mediated via CD4 receptor binding or FcR binding of anti gp120-gp120 immune complexes. Besides its effect on cytokine production, gp120 also stimulated Ig secretion in B cells from HIV-infected individuals, but not from normal donors. Finally, it was demonstrated by in situ hybridization that germinal centers of lymph nodes from HIV-infected individuals contain large amounts of HIV RNA that is in close proximity to germinal center B cells. These findings suggest that the hyperplastic germinal centers of lymph nodes provide an unique environment for virus expression and accumulation where gp120 stimulates B cells to secrete HIV inductive cytokines, such as IL-6 and TNF-alpha, and thereby further enhances virus expression in infected cells in a paracrine manner.
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PMID:Recombinant gp120 specifically enhances tumor necrosis factor-alpha production and Ig secretion in B lymphocytes from HIV-infected individuals but not from seronegative donors. 191 99

Freshly isolated B lymphocytes from patients infected with human immunodeficiency virus (HIV), in contrast to B cells from normal controls, were shown to induce viral expression in two cell lines: ACH-2, a T cell line, and U1, a promonocytic cell line, which are chronically infected with HIV, as well as in autologous T cells. In 10 out of 10 HIV-infected individuals with hypergammaglobulinemia, spontaneous HIV-inductive capacity was found with highly purified peripheral blood B cells, whereas peripheral blood or tonsillar B cells from six healthy, HIV-negative donors did not induce HIV expression unless the cells were stimulated in vitro. The induction of HIV expression was observed in direct coculture experiments of B lymphocytes and HIV-infected cells, and could also be mediated by supernatants from cultures of B cells. Significantly higher amounts of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were detected in the B cell culture supernatants from HIV-infected patients with hypergammaglobulinemia (IL-6: mean = 536 pg/ml; TNF-alpha: mean = 493 pg/ml), as compared with normal uninfected controls (IL-6: mean = 18 pg/ml; TNF-alpha: mean = 23 pg/ml). Antibodies against these cytokines abolished the HIV-inductive capacity of B cells. We conclude that in vivo activated B cells in HIV-infected individuals can upregulate the expression of virus in infected cells by secreting cytokines such as TNF-alpha and IL-6, and, therefore, may play a role in the progression of HIV infection.
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PMID:Activated B lymphocytes from human immunodeficiency virus-infected individuals induce virus expression in infected T cells and a promonocytic cell line, U1. 198 16

A series of renin inhibitors containing lactam-bridged P1-P1' dipeptide mimetics based on the ACHPA (4(S)-amino-5-cyclohexyl-3(S)-hydroxypentanoic acid) design was studied. The inhibitors were obtained by aldol addition of various lactams with N alpha-Boc-L-cyclohexylalaninal, followed by Boc group removal and acylation with Boc-Phe-His. The aldol diastereomer having the S configuration at the two newly generated stereogenic centers gave optimal enzyme inhibition. Potency was further enhanced in the gamma-lactam ring series by substitution with small hydrophobic groups to mimic the P1' side chain of the renin substrate. Thus, 2(S)-[(Boc-L-phenylalanyl-L-histidyl)amino]-3-cyclohexyl-1(S)-hydroxyl-1 - (1,5,5-trimethyl-2-oxopyrrolidin-3(S)-yl)propane (34) has an IC50 of 1.3 nM in the human plasma renin assay. A variety of substituents on the lactam nitrogen are tolerated and can be used to vary the physical properties of the inhibitor. By using a model of the human renin active site, the conformation of 34 in the enzyme-inhibitor complex is proposed. This modeled conformation is very similar to the solid-state conformation of 2(S)-[(Boc-L-phenylalanyl-L-histidyl)amino]-3-cyclohexyl-1(S)-hydroxyl- 1-(1-methyl-2-oxopyrrolidin-3(S)-yl)propane (36), the structure of which was determined by single-crystal X-ray diffraction analysis. The most potent ACH-PA-lactam renin inhibitors show good selectivity when assayed against other types of aspartic proteinases. By varying the lactam ring substituents, potent and selective inhibitors of cathepsin D and cathepsin E can be obtained.
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PMID:Renin inhibitors containing conformationally restricted P1-P1' dipeptide mimetics. 200 69


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