Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biosynthesis of arginine is an essential function for the metabolism of Mycobacterium tuberculosis (Mtb) and for the metabolism of many other microorganisms. The arginine repressor (ArgR) proteins control the transcription of genes encoding the arginine biosynthetic enzymes; they belong to repressors having one of the most intricate oligomerization patterns. Here, we present the crystal structure of the MtbArgR hexamer bound to three copies of the 20 base-pair DNA operator and to the co-repressor, L-arginine, determined to 3.3 A resolution. This is the first ternary structure of an intact hexameric ArgR in complex with its DNA operator. The structure reported here is very different from the suggested models of the ternary ArgR-DNA complexes; it has revealed the sophisticated symmetry of the complex and the presence of two remarkably different protomer conformations, folded and extended. Both features provide flexibility to DNA binding and are important for understanding the detailed function of ArgRs. Two of the 20 base-pair DNA operators align in a unified double-helical structure, suggesting the possible presence of a double ARG box in the promoter region of the Mtb arginine operon. Two pairs of protomers bind to the unified double ARG box so that the two folded protomers bind to the central half-sites of the double ARG box, whereas the two extended protomers bind to the remote half-sites. The protomers of the third pair bound to the single DNA operator also have a folded and an extended conformation. A probable mechanism for arginine repression is suggested on the basis of this structure.
 ...
PMID:The structure of the arginine repressor from Mycobacterium tuberculosis bound with its DNA operator and Co-repressor, L-arginine. 1926 6

Socioeconomic problems limit the access of drug users to health-care services. This descriptive cross-sectional study was carried out by making use of the medical records of new case tuberculosis (TB) patients hospitalized at Masih Daneshvari Hospital, the national referral centre in Iran, from 2003 to 2006. Demographic and personal characteristics of the patients and type of disease were collected and categorized. Of the 944 patients with confirmed TB, 143 (15.1%) were drug users, among whom 140 (97.9%) were men with just three women drug users. The mean age of the drug users group was 43.04 +/- 13.81 years. The type of drug used was opium in 100 cases (69.9%), heroin in 29 (20.3%), opium and heroin together in four (2.8%) and all three, opium, heroin and crack, in two (1.4%). For 238 high-risk patients, an HIV test was performed and HIV infection was confirmed in 33 cases. Patient delay was longer in drug users (P = 0.000) against other patients, whereas diagnosis delay was shorter (P = 0.007). Drug susceptibility tests were performed for 515 patients with positive cultures. One hundred and thirty-three (14.1%) were found to have 'any resistance' to anti-TB drugs, and 10 (1.1%) individuals had multidrug-resistant TB. Twenty-six (19.5%) of the individuals who showed resistance to first-line agents were drug users. There was no significant relation between drug resistance and drug use (P = 0.4). In conclusion, it seems that active case finding for TB and HIV in addict cases must be contained in harm reduction packages. Moreover, the manifestations of the disease should be considered seriously regardless of attributing them to drug use.
Int J STD AIDS 2009 May
PMID:Drug abuse profile - patient delay, diagnosis delay and drug resistance pattern - among addict patients with tuberculosis. 1938 68

This study investigated whether serious adverse events (SAEs) during antituberculosis therapy occur more frequently in HIV co-infected patients in a South African population. A retrospective analysis examined incidences of hepatotoxicity, peripheral neuropathy, severe arthralgia, persistent vomiting and severe rash in 400 patients treated for tuberculosis in a community clinic. A total of 141 patients were co-infected with HIV, among whom only 16.3% were receiving antiretrovirals. Details of SAEs were ascertainable in 331/400 patients, and occurred in 26.7% of HIV-infected and 13.3% of HIV-uninfected individuals (P = 0.003). The excess was attributable to increased peripheral neuropathy (8.3% and 1.9%, respectively, P = 0.009) and persistent vomiting (13.3% and 3.3%, P = 0.001). SAE occurrence was not related to antiretroviral use, although median CD4 counts were lower in those experiencing side-effects (130 and 259 cells/microL, P = 0.008). The treatment completion did not differ significantly between the two groups (76.6% and 84.2%, P = 0.08).
Int J STD AIDS 2009 May
PMID:Adverse events to antituberculosis therapy: influence of HIV and antiretroviral drugs. 1938 72

Thirty-six HIV-1 cases had been reported by December 2007 in Mongolia. Therefore, Mongolia has been regarded as a very low HIV-1 epidemic country, although the surveillance system is not fully developed. The aim of this study was to evaluate the risk status of HIV-1 infection in Mongolia. A total of 1415 blood samples from high-risk populations including female sex workers, men who have sex with men, mobile men, tuberculosis patients and male sexually transmitted infection (STI) clinic clients and 1050 samples from healthy controls were collected. The seroprevalences of anti-HIV-1/2, anti-Treponema pallidum, hepatitis B surface antigen (HBs Ag), anti-hepatitis C virus and hepatitis B surface antibody in the high-risk populations were 0%, 23.1%, 15.5%, 8.0% and 48.2%, and those in the controls were 0%, 3.1%, 14.7%, 4.4% and 44.4%, respectively. HIV-1 prevalence is currently low. However, according to the high prevalence of STIs in the high-risk populations, the risk status for HIV-1 infection is estimated to be high.
Int J STD AIDS 2009 Jun
PMID:High-risk status of HIV-1 infection in the very low epidemic country, Mongolia, 2007. 1945 23

AIDS-related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe the pattern of presentation and survival in Jos, Nigeria. We identified 48 HIV-positive patients with AIDS-KS and matched them for age and sex with an equal number of HIV-positive patients without AIDS-KS. We compared their clinical, immunological, virological characteristics and survival. They were similar in age and body mass index profile but patients with AIDS-KS had more tuberculosis co-infection (P, 0.02), lower median CD4 count (P, 0.003) and higher mortality (P, 0.002). Surprisingly, patients with AIDS-KS had lower levels of median viral load (29,347 copies/mL) compared with controls (80,533 copies/mL). We recommend specific AIDS-KS therapy in addition to highly active antiretroviral therapy in order to improve survival.
Int J STD AIDS 2009 Jun
PMID:Presentation and survival of patients with AIDS-related Kaposi's sarcoma in Jos, Nigeria. 1945 27

Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programmes. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1-infected drug users receiving antiretroviral therapy (ART) for at least six months in Hanoi, Vietnam. The mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA <1000 copies/mL). Correlates of viral suppression include self-reported > or = 95% adherence (P < 0.01) and current use of trimethoprim/sulphamethoxazole (P < 0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (P = 0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlight the need for adherence promotion, risk reduction programmes, and population-based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited.
Int J STD AIDS 2009 Jun
PMID:Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam. 1945 29

Acquired lymphoedema of the vulva is induced by impaired lymph flow. We present the case of a 35-year-old woman having lymphoedema of the vulva following pulmonary tuberculosis, which she had developed four years back for which she had taken a full course of antitubercular treatment for nine months from the Chest and Tuberculosis department. The biopsy taken from the perianal swellings showed hyperkeratosis and acanthosis with multiple dilated lymph specs.
Int J STD AIDS 2009 Jun
PMID:Vulval lymphoedema following pulmonary tuberculosis. 1945 36

Anaemia accelerates disease progression and increases mortality among HIV-infected individuals. Few studies have characterized this problem in developing countries. Haemoglobin values of adults presenting to an HIV tertiary care center in India between 1996 and 2007 were collected (n = 6996). Multivariate logistic regression analysis was performed to examine associations among anaemia, HIV progression and co-morbidities. Overall, anaemia prevalence was 41%. Twenty percent of patients with CD4 counts >500 cells/microL were anaemic, compared with 64% of those with CD4 counts <100 cells/microL (P < 0.001). In multivariate analysis, CD4 count <100 cells/microL (odds ratio [OR]:5.0, confidence interval [CI]:4.0-6.3), underweight body mass index (OR:4.8, CI:3.6-6.5), female gender (OR:3.1, CI:2.8-3.6) and tuberculosis (TB) (OR:1.6, CI:1.4-1.8) were significantly associated with anaemia. In this setting, management of anaemia should focus on antiretroviral therapy, nutritional supplementation and TB control. The high anaemia prevalence among patients meeting criteria for antiretroviral therapy highlights the need for increased access to non-zidovudine nucleoside reverse transcriptase inhibitors in developing countries.
Int J STD AIDS 2009 Jul
PMID:Factors associated with anaemia in HIV-infected individuals in southern India. 1954 92

The objective of this study was to determine the drug resistance prevalence and its pattern among tuberculosis (TB)-HIV patients in Iran. In this retrospective study, all admitted TB/HIV patients presenting to our tertiary centre during 2005-2007 were considered. After confirmation for TB-HIV, first-line DST was performed for culture-positive patients. The drug resistance patterns and the treatment outcomes were analysed. Of the total 92 TB/HIV patients, 27 were culture negative, and DST were available in 65. Intravenous drug abuse was seen in 59 (90.8%). Thirty-seven (57%) were 'sensitive' cases and 28 (43%) were 'any drug resistance' cases. Twenty-one (32.3%) were mono-drug, three (4.6%) poly-drug and four (6.1%) were multidrug-resistant TB patients. Previous anti-TB medication was significantly associated with any drug resistance (P = 0.041; 95% confidence interval =0.086-0.984); however, having any drug resistance did not affect the treatment outcome (P = 0.56). Streptomycin showed the highest resistance rate (27%) followed by isoniazid (20%), pyrazinamide (9.8%), rifampin (9.2%) and ethambutol (3%). Drug resistance to antitubercular agents in TB-HIV co-infected patients in Iran is high compared with other reports. Drug resistance is higher among those who have had prior anti-TB medication.
Int J STD AIDS 2009 Aug
PMID:First-line antituberculosis drug resistance prevalence and its pattern among HIV-infected patients in the national referral tuberculosis centre, Iran. 1962 90

Mycobacterium tuberculosis uses multiple mechanisms to avoid elimination by the immune system. We have previously shown that M. tuberculosis can inhibit selected macrophage responses to IFN-gamma through TLR2-dependent and -independent mechanisms. To specifically address the role of TLR2 signaling in mediating this inhibition, we stimulated macrophages with the specific TLR2/1 ligand Pam(3)CSK(4) and assayed responses to IFN-gamma. Pam(3)CSK(4) stimulation prior to IFN-gamma inhibited transcription of the unrelated IFN-gamma-inducible genes, CIITA and CXCL11. Surface expression of MHC class II and secretion of CXCL11 were greatly reduced as well, indicating that the reduction in transcripts had downstream effects. Inhibition of both genes required new protein synthesis. Using chromatin immunoprecipitation, we found that TLR2 stimulation inhibited IFN-gamma-induced RNA polymerase II binding to the CIITA and CXCL11 promoters. Furthermore, TATA binding protein was unable to bind the TATA box of the CXCL11 promoter, suggesting that assembly of transcriptional machinery was disrupted. However, TLR2 stimulation affected chromatin modifications differently at each of the inhibited promoters. Histone H3 and H4 acetylation was reduced at the CIITA promoter but unaffected at the CXCL11 promoter. In addition, NF-kappaB signaling was required for inhibition of CXCL11 transcription, but not for inhibition of CIITA. Taken together, these results indicate that TLR2-dependent inhibition of IFN-gamma-induced gene expression is mediated by distinct, gene-specific mechanisms that disrupt binding of the transcriptional machinery to the promoters.
 ...
PMID:TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms. 1962 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>