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)

Endotrypanum (order Kinetoplastida: family Trypanosomatidae) is a parasite of forest dwelling tree sloths (Edentata: genera Choleopus and Bradypus). Unique among the haemoflagellates, this protozoan has an intraerythrocytic phase in the mammalian host. Nevertheless, many striking similarities exist between Endotrypanum and the human pathogen Leishmania that make it a useful model for epidemiological and evolutionary aspects of the biology of trypanosomatids. Importantly, Endotrypanum species share both the insect vector and host reservoir with certain species of Leishmania (subgenus Viannia). Because mixed infections with Endotrypanum and Leishmania are common in sloths and, therefore, likely to occur in the sandfly vector, there is a need for adequate biochemical markers to distinguish Endotrypanum from Leishmania infections. In this paper we show that Endotrypanum promastigotes possess sialidase and trans-sialidase activities, which are absent from Leishmania, and which are not closely related to the previously described trypanosomal sialidase/trans-sialidase enzyme. We also document the occurrence in Endotrypanum of homologues of the leishmanial surface metalloproteinase gp63 genes. The combined occurrence of sialidase/trans-sialidase activities and gp63 gene homologues in a unique organism has important ramifications for both field and laboratory studies on the biology of trypanosomatids, especially those related to host infection and evolution.
Mol Biochem Parasitol 1994 Apr
PMID:Combined occurrence of trypanosomal sialidase/trans-sialidase activities and leishmanial metalloproteinase gene homologues in Endotrypanum sp. 793 5

A correlation between the ratio of the cell surface protease activity to phosphatase activity and the complexity of the pattern of cell surface exposed polypeptides of Leishmania promastigotes was demonstrated for various strains grown under similar conditions. The ratio of the cell surface protease activity to acid phosphatase activity was high for L. major and L.b. panamensis and it correlates with the expression of a single polypeptide of 63 KDa on their cell surface. Intermediate and lower ratios of these enzymatic activities relate with more complex radio-iodinated patterns: two main bands in L.b. guyanensis (70 and 58 KDa) and L.b. braziliensis (72 and 60 KDa) and three main bands 65, 50, 27 KDa in all L.m. mexicana strains tested. Evidence is presented that the acid phosphatase located on the L.m. mexicana cell surface is not an artifact due to a secondary absorption of the secreted acid phosphatase from the culture medium. These results confirm the Leishmania antigen cell surface heterogeneity. The implications on the biology of Leishmania and the clinical manifestation of leishmaniasis are discussed.
Mol Biol Rep 1993 Oct
PMID:Relationships between cell surface protease and acid phosphatase activities of Leishmania promastigote. 811 87

In SDS-PAGE the immune complexes (IC) of kala-azar patient sera showed intense bands at 55 kDa and 20 kDa corresponding to heavy and light chains of immunoglobulins. In immunoblot experiment, kala-azar and normal IC after treatment with patient sera showed multiple bands of which the band at 55 kDa was most prominent in kala-azar IC. It is known that in kala-azar sera antihuman IgG is present, so the heavy band at 55 kDa region may be due to higher amount of IgG and/or other antigen(s) present at that region. Immunoblot experiments of kala-azar IC with anti gp63 also developed a major band at 55 kDa. It suggests that the antigen (55 kDa) and gp63 have common antigenic epitope (s). Normal IC did not react with anti gp63 indicating absence of this antigen in normal IC. Antigenic similarity between the IC antigen (55 kDa) and gp63 indicated that the former antigen may have been processed from gp63. In summary, identification of a parasite antigen (55 kDa) in IC of kala-azar patients sera may be useful in developing a serodiagnostic assay for visceral leishmaniasis.
Mol Cell Biochem 1994 Jan 12
PMID:Immunoblotting identifies an antigen recognized by anti gp63 in the immune complexes of Indian kala-azar patient sera. 819 Jan 17

The goal of this work was to investigate the mechanism of drug resistance in Leishmania enriettii as a model system for drug resistance both in human leishmaniasis and on other parasitic diseases. Parasites were selected in increasing concentrations of vinblastine, an inhibitor of microtubule assembly, and resistant clones were isolated which grew in concentrations 5-30 times the IC50 (30 micrograms ml-1) of parental cells. The vinblastine-resistant parasites were also resistant to puromycin, an unrelated drug which inhibits protein synthesis. This cross-resistance to unrelated drugs had previously been observed in mammalian cells and recently in L. donovani. The proposed mechanism for this cross-resistance is drug efflux mediated by increased expression of a P-glycoprotein molecule encoded by a multidrug resistance (mdr) gene. Here we report the identification, cloning and sequencing of an mdr-like gene from L. enriettii, lemdr1, and demonstrate that this gene is amplified on an extrachromosomal circle of 35-40 kb in vinblastine-resistant L. enriettii. The longest open reading frame in the cloned gene is 1280 amino acids with a predicted protein of 140 kDa. The predicted protein has a structure similar to that for all other reported P-glycoproteins namely 12 transmembrane domains and 2 ATP binding sites, arranged in 2 similar half-molecules. Comparison of the primary amino acid sequence with other known mdr gene products demonstrates a significant homology with 37% amino acid identity with human mdr1 and 83% identity with the L. donovani ldmdr1 gene. The lemdr1 gene was cloned in the expression vector pALTNEO and transfected into wild-type L. enriettii and the resulting transfected cells were resistant to vinblastine but at lower levels than in the selected mutant cells.
Mol Biochem Parasitol 1993 Aug
PMID:Cloning and functional analysis of an extrachromosomally amplified multidrug resistance-like gene in Leishmania enriettii. 823 12

The extent of the covalent cross-linking of collagen molecules by pyridinoline was measured in skin lesions from patients with chromomycosis, a chronic fungal infection leading to an extensive and chronic dermal fibrosis. These data were compared to those collected from patients with a localized cutaneous leishmaniasis, an acute inflammatory process leading to an extensive and reversible remodelling of the extracellular matrix. The amount of the mature cross-linking amino acid pyridinoline increased in chromomycosis patients when compared to controls and was significantly higher than in leishmaniasis patients. These data confirm and extend our previous studies on liver fibrosis showing that a high level of pyridinoline is associated to irreversible fibrotic lesions. They also suggest that an increase in the mature collagen cross-linking by pyridinoline in the course of fibrosis is not restricted to liver, but might be a general feature of irreversible and chronic fibrosis.
Cell Mol Biol (Noisy-le-grand) 1993 Nov
PMID:Collagen cross-linking by pyridinoline occurs in non-reversible skin fibrosis. 826 58

Leishmanial parasites routinely undergo cyclic differentiation from promastigotes to amastigotes during their life cycle. This process involves both morphological and macromolecular changes. To study such changes, we used a axenic culture system which permits the continuous generation and cycling of Leishmania donovani from promastigotes to 'amastigotes' in vitro. cDNA libraries were constructed from poly(A)+ RNA isolated from both the pro- and amastigote forms. Using differential cDNA hybridization techniques, 3 unique cDNAs clones (P17, A41 and A45) were isolated from the amastigote library. To assess whether these clones were differentially expressed by the pro-or 'amastigotes' forms, they were hybridized to RNA isolated from each of these parasite forms in Northern and slot-blots. Results of these analyses showed that 'amastigotes' had approx. 2-fold higher levels of the A41 and A45 RNAs compared to the promastigotes. Conversely, promastigotes showed approx. 2-fold higher levels of the P17 RNA than 'amastigotes'. Nucleotide sequence analysis and comparison with those in Gene bank, revealed that the 3 cDNAs represent unique leishmanial genes. Comparison of the deduced amino acid sequences revealed that P17 open reading frame (ORF) had significant similarity with a soybean ribosomal protein S11; A41 ORF with a Bacillus subtilis spore germination gene (gerC) and A45 ORF with yeast stress-inducible protein (STI1). It is of interest to note that, of the 3 cDNAs identified, the A45-encoded protein was recognized by sera from patients with clinically active visceral leishmaniasis and was encoded by a single copy gene.
Mol Biochem Parasitol 1993 Apr
PMID:Cloning and characterization of differentially expressed genes from in vitro-grown 'amastigotes' of Leishmania donovani. 847 59

The gene encoding the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme from Leishmania donovani has been cloned and sequenced. The hgprt open reading frame encoded a polypeptide of 211 amino acids that exhibited 3 regions of significant homology with other eukaryotic HGPRTs and a C-terminal tripeptide compatible with a glycosomal targeting signal. Northern blot analysis of L. donovani RNA revealed two hgprt transcripts, a 1.9-kb mRNA and a 1.7-kb transcript. The expression of the 1.7-kb hgprt mRNA and the activity of HGPRT enzyme were both augmented approx. 5-fold in parasites incubated in the absence of purines. Southern blots of genomic DNA indicated only a single hgprt locus within the L. donovani genome. Overexpression of L. donovani hgprt in E. coli complemented genetic deficiencies in hypoxanthine and guanine phosphoribosylating activities and yielded abundant quantities of enzymatically active HGPRT. The recombinant HGPRT was purified to homogeneity and recognized hypoxanthine, guanine and allopurinol, but not adenine or xanthine, as substrates. The hgprt clone and pure HGPRT protein provide essential reagents for validating HGPRT as a therapeutic target for the treatment of leishmaniasis and other diseases of parasitic origin.
Mol Biochem Parasitol 1995 Jul
PMID:Cloning and expression of the hypoxanthine-guanine phosphoribosyltransferase from Leishmania donovani. 857 21

When infected with Leishmania species, patients develop specific antibodies that constitute the basis of serodiagnosis. using Western blot analysis we studied the specificity of anti-leishmania donovani antibodies in patients with visceral leishmaniasis, healthy subjects living in an endemic and non-endemic areas, and patients of other infectious diseases like malaria, leprosy, tuberculosis and tropical splenomegaly. Sera from patients with kala-azar recognised numerous antigens that had a molecular weight of 150 KD, 145 KD, 120 KD, 92 KD, 87 KD, 72 KD, 65 KD, 56 KD, 50 KD, 40 KD, 26 KD, 21 KD, 14 KD, AND 12 KD. The 150, 145, 120, 92, 87, 81, 65, 25, 21, 14, and 12 KD antigens had the greatest specificity for kala-azar sera while the bands of molecular weights 72, 56, 50, and 40 KD were found to be cross reactive with sera of patients of other diseases.
Biochem Mol Biol Int 1995 Nov
PMID:Evaluation of antibody responses in Indian kala-azar by immunoblot. 862 3

A minisatellite DNA sequence is described for the first time in Leishmania infantum. It is borne by four chromosomes and consists of an 81-bp repeat unit organised in several clusters. On chromosomes I and V of L. infantum, the clusters are tightly located in the size-variable subtelomeric regions. The organisation of this sequence may be related to that of the subtelomeric interspersed repeat sequences identified in the human genome. The sequencing of seven repeat units, some subcloned from the same cluster, allowed the definition of a consensus sequence of 81 bp, particularly G/C rich (73%). Two subfamilies were clearly defined: one exhibits a 91-95% homology with the consensus sequence; the second one comprises two monomers sharing a 91% homology but only 77% homology with the consensus sequence. The two types of monomers can be found in the same cluster. These data suggest interactions between monomers and a possible role of this sequence in the instability of these regions. Finally, restriction fragment length polymorphisms were revealed by this sequence among various strains of L. infantum. Besides allowing the detection of recombination events in the unstable regions of the chromosomes, this new marker may become a useful tool in the study of the parasite population dynamics in leishmaniasis foci.
Mol Biochem Parasitol 1995 Oct
PMID:A polymorphic minisatellite sequence in the subtelomeric regions of chromosomes I and V in Leishmania infantum. 871 43

We examined the effect of genetic background on Th1/Th2 development. We discuss data demonstrating that genetic background is an important determinant of interleukin-12 (IL-12) responsiveness and the potential implications for disease progression in murine experimental leishmaniasis. Genetic analysis of the differential control of IL-12 responsiveness led to the identification of a controlling locus on the middle portion of murine chromosome 11. This genetic region (or its human counterpart, 5q31) has been associated with increased disease susceptibilities for several atopic, infectious, and autoimmune disorders. We discuss potential roles for genetic control of IL-12 responsiveness in the development of these diseases.
J Mol Med (Berl) 1997 Jul
PMID:Genetic control of interleukin 12 responsiveness: implications for disease pathogenesis. 925 13


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