Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary tuberculosis (TB) has re-emerged in relation to the HIV epidemic. To gain knowledge of TB infection in HIV-infected patients, we studied 106 HIV-TB cases in a cohort of 2,646 patients in Puerto Rico between January 1992 and September 1999. The TB prevalence was 4%; 82% were males and 73.6% were injecting drug users (IDU). At the time of TB diagnosis, the mean CD4+ T-cell count was 174/mm3, 35% were in antiretroviral treatment and 42.5% had another AIDS related condition. Only 9% received two or more antiretroviral medications. The death rate in the first year after the TB diagnosis was 55%. A Cox proportional hazard analysis showed that CD4+ T-cells <200/mm3 (p<0.01), history of toxoplasmosis (p<0.01), wasting syndrome (p<0.01) and lack of antiretroviral treatment (p=0.12) increased their mortality risk. The studied patients had a highly compromised immune system at the time of TB diagnosis. Low CD4+ T-cells (essential to control the TB infection) significantly increased the hazard and mortality risk of the cases studied. Early antiretroviral therapy in combination is recommended in HIV-infected patients, particularly in those with IDU, TB history and low CD4+ T-cell levels, to ensure an optimal immune system function that limits the pulmonary TB morbidity and mortality.
Cell Mol Biol (Noisy-le-grand) 2001 Nov
PMID:Pulmonary tuberculosis mortality risks in a cohort of HIV/AIDS patients in Puerto Rico. 1183 62

The cGMP-dependent protein kinase (PKG) of Eimeria tenella and Toxoplasma gondii is the target of a novel coccidiostat that is effective against coccidiosis and toxoplasmosis in animal models. Preparations of native PKG enzyme from Toxoplasma and Eimeria contain a membrane-associated polypeptide (isoform-I) of about 110 kDa and a slightly smaller soluble polypeptide (isoform-II). Expression of T. gondii and E. tenella PKG cDNA clones in Toxoplasma yield similarly sized recombinant polypeptides, which co-migrate on SDS-polyacrylamide gels with the corresponding native isoforms. Results of targeted mutagenesis of potential translational initiation sites suggest that parasite isoform-II is a product of alternative translational initiation from an internal initiator methionine codon. Exclusive expression of isoform-II or isoform-I can be achieved by preventing initiation at the respective primary or secondary sites. Immunofluorescence analysis indicates that recombinant isoform-I localizes primarily to the parasite plasma membrane, while isoform-II remains cytosolic. Mutagenesis and metabolic labeling studies reveal that the observed membrane-association of full-length recombinant PKG is mediated by N-terminal myristoylation and palmitoylation at amino acids G2 and C4. We also confirm the functional significance of a putative third PKG allosteric site, common to apicomplexan PKGs but absent from vertebrate or insect PKGs. In assays with transiently transfected parasites, constructs harboring a mutation at this site express markedly lower levels of cGMP-dependent PKG activity, while a triple mutant bearing mutations in all three sites reduces kinase activity to background levels.
Mol Biochem Parasitol 2002 Apr 09
PMID:Molecular characterization of a coccidian parasite cGMP dependent protein kinase. 1189 22

Motion is an intrinsic property of all living organisms, and each cell displays a variety of shapes and modes of locomotion. How structural proteins support cellular movement and how cytoskeletal dynamics and motor proteins are harnessed to generate order and movement are among the fundamental and not fully resolved questions in biology today. Protozoan parasites belonging to the Apicomplexa are of enormous medical and veterinary significance, being responsible for a wide variety of diseases in human and animals, including malaria, toxoplasmosis, coccidiosis and cryptosporidiosis. These obligate intracellular parasites exhibit a unique form of actin-based gliding motility, which is essential for host cell invasion and spreading of parasites throughout the infected hosts. A motor complex composed of a small myosin of class XIV associated with a myosin light chain and a plasma membrane-docking protein is present beneath the parasite's plasma membrane. According to the capping model, this complex is connected directly or indirectly to transmembrane adhesin complexes, which are delivered to the parasite surface upon microneme secretion. Together with F-actin and as yet unknown bridging molecules and proteases, these complexes are among the structural and functional components of the 'glideosome'.
Mol Microbiol 2002 Aug
PMID:'The glideosome': a dynamic complex powering gliding motion and host cell invasion by Toxoplasma gondii. 1213 8

Near-infrared Raman spectroscopy (NIRS) is a particularly promising technique that is being used in recent years formany biomedical applications. Optical spectroscopy has gained increasing prominence as a tool for quantitative analysis of biological samples, clinical diagnostic, concentration measurements of blood metabolites and therapeutic drugs, and analysis of the chemical composition of human tissues. Toxoplasmosis is an important zoonosis in public health, and domestic cats are the most important transmitters of the disease. This disease can be detected by several serological tests, which usually have a high cost and require a long time. The goal of this work was to investigate a new method to diagnosis Toxoplasma gondii infections using NIRS. In order to confirm antibody detection, 24 cat blood serum samples were analyzed by the Raman spectra, from which 23 presented positive serology to toxoplasmosis and one was a reference negative serum. Characteristic Raman peaks allowed differentiation between negative and positive sera, confirming the possibility of antibody detection by Raman spectroscopy. These results give the first evidence that this technique can be useful to quantify antibodies in cat sera.
Cell Mol Biol (Noisy-le-grand) 2002 Jul
PMID:Use of near-infrared raman spectroscopy to detect IgG and IgM antibodies against Toxoplasma gondii in serum samples of domestic cats. 1214 16

Toxoplasma gondii is a ubiquitous pathogen that causes significant morbidity and mortality in immunocompromised patients. Although relatively uncommon, toxoplasmosis is increasingly recognized as a severe complication of hematopoietic stem cell transplantation. Timely and accurate diagnosis of this treatable infection is critical. PCR-based testing has become the preferred method for diagnosis, occasionally replacing tissue biopsy. This article reviews the clinical, diagnostic and therapeutic aspects of toxoplasmosis in the setting of hematopoietic stem cell transplantation and the current and future role of PCR-based testing for early detection and diagnosis.
Expert Rev Mol Diagn 2002 Nov
PMID:PCR for the diagnosis of toxoplasmosis after hematopoietic stem cell transplantation. 1246 57

A representative collection was obtained containing 68 monoclonal antibodies (MAB) to Toxoplasma gondii antigens, which was characterized by the binding with the below fractions of tochizoites in the immune-enzyme assay (IEA) and immunoblotting (IB): membrane (MEM), somatic (water-soluble, SOM) and excretory-secretory (ES). Most of MABs were produced to MEM antigens (43), 6 MABs reacted with the somatic fraction, and 3 MABs reacted with both fractions. Two MABs to ES antigen were detected in the latter group. An analysis of MABs in concurrent IEA and IB revealed the immune-dominant proteins of the MEM and SOM fractions of antibodies to T. gondii tochizoites (p30 and p27, respectively). The presence of 2 non-overlapping antigenic determinants was shown for p30. Further research would detect MABs that could be used in the diagnosis of toxoplasmosis.
Mol Gen Mikrobiol Virusol 2003
PMID:[Production and characterization of a panel of monoclonal antibodies to Toxoplasma gondii antigens]. 1466 58

Recurrent pneumonia (RP) within 12 months is one of the AIDS diagnosis criteria. To gain knowledge of RP infection in HIV-infected patients, we studied 145 RP cases detected in a cohort of 2,996 HIV patients in Puerto Rico between Jan. 1992-Dec. 2001. The RP prevalence was 4.8%; 77.2% were males and 62.1% were injecting drug users (IDU). At the time of RP diagnosis, the mean CD4+ T cell count was 93.8 cells/mm3, 59.3% were in antiretroviral treatment, 13% had received the pneumococcal vaccine and 84.8% had another AIDS related condition. Over 37% received two or more antiretroviral medications. The death rate in the first year after the RP diagnosis was 63.4%. A Cox proportional hazard analysis showed that CD4+ T cells <200/mm3 (p<0.05), history of toxoplasmosis (p<0.01), wasting syndrome (p<0.01), esophageal candidiasis (p<0.05) and lower number of antiretroviral medications (p<0.05) increased their mortality risk. The studied patients had a highly compromised immune system and a very low pneumococcal vaccination percent at the time of RP diagnosis. Low CD4+ T cells significantly increased the hazard and mortality risk of the cases studied. Antecedents of antiretroviral therapy in these patients ensure a better outcome with lower mortality. Efforts to increase the vaccination rate should reduce the RP incidence in our HIV-infected population.
Cell Mol Biol (Noisy-le-grand) 2003 Dec
PMID:Recurrent pneumonia mortality risk in a HIV/AIDS Puerto Rican cohort. 1498 87

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis in humans and animals. To invade host cells, T. gondii deploys the contents of its apically oriented secretory organelles that include the micronemes. Contained within the micronemes are proteins that possess adhesive motifs resembling those found in mammalian proteins. The micronemal protein MIC2 is a member of the thrombospondin-related anonymous protein (TRAP) family of adhesive proteins, which characteristically feature at least one integrin-like A-domain. Because of its strict conservation within the family, we sought to define the role of this domain by testing the adhesive properties of recombinant MIC2 A-domain fusion proteins. Since MIC2 is found as a multimeric species in parasite lysate, we also wanted to test whether recombinant MIC2 A-domain bound to its substrate in a multimeric state. In vitro assays of binding to several different potential receptors revealed that the MIC2 A-domain binds specifically to heparin, a ubiquitous sulfated proteoglycan found in the extracellular matrix (ECM). Additional studies demonstrated that this binding is not dependent on the MIDAS site, a well-conserved divalent cation-binding motif that the MIC2 A-domain shares with its mammalian counterparts. The recombinant MIC2 A-domain bound to heparin as a high molecular weight species, as did MIC2 from parasite lysate, indicating that the recombinant A-domain mimics the binding of native MIC2. Multimerization of MIC2 may increase the number of interactions with host cell receptors, thereby forming a multivalent adhesive junction during parasite entry.
Mol Biochem Parasitol 2004 Apr
PMID:Multimerization of the Toxoplasma gondii MIC2 integrin-like A-domain is required for binding to heparin and human cells. 1500 40

Single-celled apicomplexan parasites are known to cause major diseases in humans and animals including malaria, toxoplasmosis, and coccidiosis. The presence of apicoplasts with the remnant of a plastid-like DNA argues that these parasites evolved from photosynthetic ancestors possibly related to the dinoflagellates. Toxoplasma gondii displays amylopectin-like polymers within the cytoplasm of the dormant brain cysts. Here we report a detailed structural and comparative analysis of the Toxoplasma gondii, green alga Chlamydomonas reinhardtii, and dinoflagellate Crypthecodinium cohnii storage polysaccharides. We show Toxoplasma gondii amylopectin to be similar to the semicrystalline floridean starch accumulated by red algae. Unlike green plants or algae, the nuclear DNA sequences as well as biochemical and phylogenetic analysis argue that the Toxoplasma gondii amylopectin pathway has evolved from a totally different UDP-glucose-based metabolism similar to that of the floridean starch accumulating red alga Cyanidioschyzon merolae and, to a lesser extent, to those of glycogen storing animals or fungi. In both red algae and apicomplexan parasites, isoamylase and glucan-water dikinase sequences are proposed to explain the appearance of semicrystalline starch-like polymers. Our results have built a case for the separate evolution of semicrystalline storage polysaccharides upon acquisition of photosynthesis in eukaryotes.
J Mol Evol 2005 Feb
PMID:Evolution of plant-like crystalline storage polysaccharide in the protozoan parasite Toxoplasma gondii argues for a red alga ancestry. 1578 54

The hormonal form of Vitamin D, 1,25-dihydroxyvitamin D3, is well known for its immunosuppressive, anti-proliferative and pro-apoptotic activities. In the present work, we studied the effect of 1,25-dihydroxyvitamin D3 on Toxoplasma gondii-infected mice. We observed that 1,25-dihydroxyvitamin D3 reduces the survival rate of infected mice by up to 37% at day 10 post-infection compared to untreated infected mice (P < 0.0001). IFN-gamma and IL-12p40 levels were significantly reduced by 1,25-dihydroxyvitamin D3 in infected mice sera indicating an inhibition of Th-1-type cytokines. CD4+ T lymphocyte and splenocyte counts were also reduced following 1,25-dihydroxyvitamin D3 treatment and a marked induction of apoptosis, accompanied with down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-X(L), was observed. The above results indicate that 1,25-dihydroxyvitamin D3 induces splenocyte apoptosis and enhances host susceptibility to toxoplasmosis.
J Steroid Biochem Mol Biol 2005 Jul
PMID:1,25-Dihydroxyvitamin D3 induces splenocyte apoptosis and enhances BALB/c mice sensitivity to toxoplasmosis. 1593 87


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