Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoriasis usually occurs many years before development of arthritis. This is a case report of a patient with acute polyarthritis affecting both peripheral joints and the left sacroiliac joint, preceding the appearance of typical skin manifestations for almost two months. A 44-year-old male mechanic was admitted to our institution for acute additive polyarthritis. Inflammatory synovitis primarily affected large peripheral joints (knees, ankles) in an asymmetrical pattern, with a concomitant development of unilateral sacroiliitis and later with asymmetrical involvement of several proximal and distal interphalangeal joints of the hands and feet. There were also signs of enthesopathy of the right heel. Arthritis was not proceeded by infection of the lower genital or gastrointestinal tract or serological and bacteriological evidences of streptococcal or HIV infection. Laboratory findings showed an erythrocyte sedimentation rate (92 in the first hour), positive histocompatibility antigen HLA-B27 and an increased level of acute phase reactants. Almost two months after affecting the locomotor system a typical psoriatic rash developed, first affecting the scalp and then spreading over the trunk and extremities. It was accompanied by severe onychodystrophy. The patient underwent intensive treatment with methylprednisolone (1.5 mg/kg) and cyclosporine A with significant results.
 ...
PMID:[Psoriatic arthritis: case report of acute HLA-B27 positive polyarthritis preceding the onset of typical skin changes]. 947 36

We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML.
 ...
PMID:[Acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy treated with highly active anti-retroviral therapy]. 1121 4

The reverse transcriptase (RT) of HIV which has been inhibited by the incorporation of AZT into the primer strand is subject to a deblocking reaction by cellular ATP. This reaction yields unblocked primer plus the dinucleoside tetraphosphate, AZTp(4)A. In the present study, we report that AZTp(4)A is an excellent substrate for the enzyme Ap(4)A hydrolase (asymmetrical dinucleoside tetraphosphatase, EC 3.6.1.17), an enzyme that is widely distributed in many cell types. Progress of the reaction has been monitored by 31P NMR, and it was found that hydrolysis results in the production of AZTTP:ATP in a 7:1 ratio. The AZTp(4)A was also hydrolyzed at a rate 1.8-fold more rapidly than Ap(4)A. Spectrophotometric assays yielded Michaelis constants of 2.35 and 0.71 microM for Ap(4)A and AZTp(4)A, respectively. It, therefore, appears that Ap(4)A hydrolase can play a useful role in the regeneration of the AZTTP, the active form of AZT, for the inhibition of HIV RT.
 ...
PMID:Metabolic transformation of AZTp4A by Ap4A hydrolase regenerates AZT triphosphate. 1276 70

Prospective studies of HIV-positive and HIV-negative individuals, longitudinal prospective studies of HIV-positive patients and the African experience with spondyloarthropathies have provided support for a direct role of HIV infection in producing a variety of articular manifestations. The most common manifestations are arthralgia and the spectrum of spondyloarthropathies, but distinct entities such as HIV-associated arthritis and the painful articular syndrome have also been reported. Although initial reports described patients with mainly asymmetric oligoarthritis, a polyarticular presentation is now seen frequently. In Caucasians, HIV-associated reactive arthritis resembles reactive arthritis in non-HIV-infected persons. Reactive arthritis, psoriatic arthritis and undifferentiated spondyloarthropathy were uncommon in Africa and are now detected more often with the HIV epidemic. Although early reports in Western communities reported asymmetrical oligoarthritis as the usual pattern, polyarticular involvement is now seen frequently. Intravenous drug abuse is the most likely risk factor for septic arthritis, even in HIV-infected persons in Western communities, while HIV infection itself may be more important in developing countries where most patients do not receive highly active antiretroviral therapy (HAART). Recent reports have drawn attention to the development of avascular necrosis of the bone in HIV-positive patients and the risk factors include HAART itself, complications of HAART, HIV infection per se or concomitant conventional risk factors. Many patients respond to conventional symptomatic therapy, and disease-modifying drug therapy is necessary for patients who have persistent and progressive arthritis. The use of HAART can modify the prevalence or expression of the articular syndromes.
 ...
PMID:Articular manifestations of human immunodeficiency virus infection. 1278 25

A patient of ALS-like disorder in an HIV-1 clade-C-infected heterosexual male is being reported. A 37-year-old gentleman presented with subacute, progressive asymmetrical onset of weakness and wasting of upper limbs associated with brisk muscle stretch reflexes and without any sensory or sphincter involvement. While nerve conduction tests were normal, the EMG of proximal and distal limb muscles on both sides revealed evidence of denervation and reinnervation. Routine blood and urine tests and investigations for underlying causes of motor neuron disease were noncontributory. He was HIV-1, subtype clade C seropositive. A diagnosis of HIV-related anterior horn cell disease was considered and zidovudine, lamivudine and nevirapine were started. After 1 month, there was a subjective improvement of 10% and objective improvement in strength of muscles of proximal upper limb on both sides by one grade power on MRC scale. Reports of amyotrophic lateral sclerosis (ALS)-like illness in HIV are sparse. The reversibility of "ALS"-like features in this subgroup of patients might offer an insight into the pathogenesis of amyotrophic lateral sclerosis. This is a first report of ALS-like illness caused by subtype C of HIV-1 strain.
 ...
PMID:HIV-1 clade-C-associated "ALS"-like disorder: first report from India. 1545 Jul 78

The active site of aspartic proteases is covered by one or more flaps, which control access to the active site and play a significant role in the binding of the substrate. An extensive conformational change of the flaps takes place upon binding of substrate to the active site. A long molecular dynamics simulation was performed on the complex consisting of a peptide (CA-p2) from a natural substrate cleavage site of the gag/pol polyprotein placed in the active site of HIV-1 protease (PR) with an open flap conformation. During the simulation, the substrate induced the closing of the flaps into the closed conformation in an asymmetrical way through a hydrophobic intermediate state cluster. The nature of the residues of HIV-1 PR identified to be important in the flap closing mechanism is conserved across known structures of retroviral aspartic proteases family. The flap closing mechanism described in HIV-1 PR is proposed to be a general model for flap closing in retroviral aspartic proteases.
 ...
PMID:Closing of the flaps of HIV-1 protease induced by substrate binding: a model of a flap closing mechanism in retroviral aspartic proteases. 1671 71

The SL1 stem-loop located in the encapsidation domain is responsible for initiating the dimerisation of HIV-1 genomic RNA by means of a loop-loop interaction known as Kissing Complex (KC). The SL1 secondary structure has been predicted as a 35 nucleotides [K. G. Murti, M. Bondurant, and A. Tereba. J Virol 37, 411-419 (1981)] stem-loop composed of a 4 base pairs (bp) terminal duplex, a 4 nt asymmetrical internal loop, a 7 bp internal duplex, and a 9 nt apical loop. Several high resolution structures of the monomer and of KC of a 23 nt sequence containing only the internal duplex and the apical loop of SL1 are available in the literature. No experimental high resolution structure of the complete native SL1 sequence has been reported so far, either for the monomer or for KC. The asymmetrical internal loop has been described from NMR studies of different monomeric hairpin sequences, leading to divergent results, which suggests its high flexibility. In this work, we built a SL1(35) KC model which was submitted to a 31 ns molecular dynamics simulation (MD). Our results allows to describe the internal dynamics of SL1(35) KC and the differences of behavior of the different parts of the dimer. Thus, we could show the stability of the interactions between the two apical loops and of the terminal duplexes, the destabilization of the internal duplexes and the high flexibility of the asymmetrical internal loops.
 ...
PMID:Molecular dynamics simulation for probing the flexibility of the 35 nucleotide SL1 sequence kissing complex from HIV-1Lai genomic RNA. 1731 92

Malawi, a very poor country located in southern Africa, is no exception to the growing trend and severity in HIV prevalence. By the end of 2003 there were 900 000 adults and children in Malawi living with HIV/AIDS. Adult prevalence was estimated to be 15%, which is higher than the 7.1% average rate for sub-Saharan Africa. In order to understand the spread of HIV/AIDS it is imperative to address the economic, social, cultural, and political issues that impact on women's contraction and spread of the virus. We do so in this paper by critically examining the gendered context of HIV/AIDS with reference to Malawi. The theoretical framework for this research focuses on poverty, gender relations, regional migration patterns, and global economic changes which place women in highly vulnerable situations. The study was conducted in a low-income area in Lilongwe, the capital city of Malawi. In 2003 and 2004, 60 randomly selected women who lived in a low socioeconomic residential area completed a structured interview on issues concerning individual economic situations, marriage history, fertility, family planning and social networks, gender, sexual partnerships, and HIV/AIDS. Focus group interviews were also conducted with an additional 20 women. The results of our study indicate that the rising epidemic among women in Malawi is firstly driven by poverty which limits their options. Secondly, gender inequality and asymmetrical sexual relations are basic to spreading HIV/AIDS among women. Thirdly, in spite of their awareness through media and health care professionals, women are unable to protect themselves, which further increases their vulnerability.
 ...
PMID:Women in Chinsapo, Malawi: vulnerability and risk to HIV/AIDS. 1760 Sep 74

The SL1 stem-loop is the dimerization initiation site for linking the two copies of the RNA forming the HIV-1 genome. The 26 nucleotides stem contains a defect consisting on a highly conserved G-rich 1-3 asymmetrical internal loop, which is a major site for nucleocapsid protein binding. Several NMR attempts were undertaken to determine the internal loop structure in the SL1 monomer. However, the RNA constructs used in the different studies were largely mutated, in particular with replacement of the nine nucleotides apical loop by a tetraloop, and divergent results were obtained ranging from a rigid structure to a particularly large flexibility. To investigate the reasons for such discrepancies, we used molecular dynamics simulation of the SL1 monomer to probe the effect of mutations on the conformational stability of the internal loop and of the whole stem. It is found that in the wild-type sequence, the internal loop displays conformational variability originating mainly from the nine nucleotides apical loop flexibility that causes large conformational fluctuations (without changing the average structure) in the 7 bp duplex linking the apical and internal loops. The large amplitude atomic motions in the duplex are transmitted to the internal loop in which they induce conformational changes characterized by a labile hydrogen bond network such as G5 successively H-bonded to A29 and G30. On the contrary, with a four nucleotides apical loop, conformational fluctuations in the duplex are reduced by a factor of 2 and are not sufficiently energizing for promoting changes in the internal loop structure at the time scale of the simulations.
 ...
PMID:Insight into the intrinsic flexibility of the SL1 stem-loop from genomic RNA of HIV-1 as probed by molecular dynamics simulation. 1800 23

As part of the Microbicides Development Programme, we conducted formative research to explore perceptions of anal sex at a site in rural KwaZulu-Natal. We were interested in the practice of anal sex because of its potential role in HIV transmission. Eleven focus group discussions were conducted with men and women from rural areas and in a semi-urban township. Participants were asked about their knowledge of and attitudes towards anal sex, and its practice in the local population. Findings indicate that in discussion anal sex was confused with other non-traditional sexual practices like vaginal sex 'dog-style' and with oral sex. Discussion of anal sex among those who had heard about it linked it to socially marginal groups and asymmetrical power relations.
 ...
PMID:Perceptions of anal sex in rural South Africa. 1824 12


<< Previous 1 2 3 4 Next >>