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)

1. Mice were infected with fertile bisexual Schistosoma mansoni and compared with similar animals infected with unisexual worms or sterile bisexual worms. 2. A significant increase in splenic weight occurred in all infected animals. 3. Administration of well-tolerated doses of 6-mercaptopurine abolished the increase in relative splenic weight in animals infected with ordinary S. mansoni. 4. In splenectomized uninfected mice leucocytosis but no other haematological changes developed. 5. In splenectomized mice lower values for packed cell volume were observed 8 weeks after, but not 12 weeks after, infection with S. mansoni. 6. Slight prolongation of the life-span of erythrocytes occurred in splenectomized infected mice. 7. It is concluded that anaemia in schistosomiasis depends to a significant extent on immunity developed to adult schistosomal worms and can develop in the absense of schistosomal ova. 8. The anaemia resulting from such an immune response may be suppressed by administration of 6-mercaptopurine. 9. Such anaemia occurs even in splenectomized mice; thus hypersplenism is not necessary for its development although splenectomy slightly prolongs the erythrocyte life-span.
Clin Sci Mol Med 1978 Apr
PMID:The causation of splenomegaly in schistosomiasis in mice. 63 70

The effect of serotonin on the fluidity of the tegumental membranes of adult male Schistosoma mansoni was assessed by the fluorescence recovery after photobleaching technique. It was demonstrated that the translational diffusion of 5-N'-octadecanoyl aminofluorescein is reduced by a mechanism involving G-protein coupled activation of adenylate cyclase and lowering of intracellular calcium concentration. Furthermore, the lateral diffusion coefficient and the mobile fraction appear to be controlled by calcium and cAMP dependent pathways respectively. No change in the diffusion of the fluorescent phospholipid N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-phosphatidyl choline was observed, suggesting the two probes used here partition into two different domains that are under independent control. An increase in the amount of protein associating with a membrane cytoskeleton is also demonstrated.
Mol Biochem Parasitol 1992 Jul
PMID:Changes in the lateral diffusion of fluorescent lipid analogues in the surface membrane of adult male Schistosoma mansoni. 132 59

Several cDNA clones encoding a 21.7-kDa antigen (Sm21.7) were detected from a Schistosoma mansoni sporocyst cDNA expression library using irradiated cercaria-vaccinated rabbit serum. The antigen was designated 'vaccine dominant' because parasite-derived Sm21.7 was recognised preferentially by mouse vaccine sera compared with mouse infection sera. The cDNA and corresponding gDNA sequences showed 64% identity at the nucleotide level and 47% identity at the amino acid level with the sequence of a previously described S. mansoni tegumental antigen, sma22.6. Whereas sma22.6 mRNA occurs almost exclusively in the adult worm, Sm21.7 mRNA was equally abundant in the sporocyst, schistosomular and adult stages. Both Sm21.7 and sma22.6 sequences reveal a motif strongly homologous to the EF hand calcium binding domain but lacking the invariant glycine in the calcium binding loop. The disruptive nature of the glutamine which in Sm21.7 replaces the glycine explains why the motif is non-functional, as shown by the inability of Sm21.7 to bind calcium.
Mol Biochem Parasitol 1992 Feb
PMID:Cloning of a 21.7-kDa vaccine-dominant antigen gene of Schistosoma mansoni reveals an EF hand-like motif. 137 27

Soon after infecting a mammalian host, cercariae of Schistosoma mansoni rapidly undergo a series of morphologic and biochemical adaptations associated with transformation to their next developmental stage, the schistosomulum. Few of these changes are associated with alterations in gene expression except for an apparent increase in protein synthesis. By pulse-labeling, we demonstrate that there is a gradual rise in methionine incorporation after transformation, and that the rise is not due to increasing amino acid uptake or increasing protein stability. This pattern of protein synthesis did not result from a general increase in transcription of mRNA. There was likewise no evidence of a rise in the availability of selected rate limiting components of the translational machinery such as rRNA or elongation factor 1 alpha as a mechanism for increasing levels of translation. Transcription of HSP 70 appears to be induced in both cercariae and schistosomula, though translation of this message was not detected. A comparison between the level of in vivo synthesis of proteins and the level of their corresponding mRNAs suggests that following transformation of cercariae to schistosomula the translation of most mRNAs is blocked and that this block is gradually reversed during the first 24 h.
Mol Biochem Parasitol 1992 Apr
PMID:Developmental regulation of protein synthesis in schistosomes. 137 60

At least 3 structural protein precursors of the eggshell are synthesized and stockpiled in the extensive vitelline cells of the liver fluke Fasciola hepatica L. One of these, vitelline protein B, consists of a closely related family of proteins that owes its apparent electrophoretic heterogeneity to variations in the Tyr to DOPA conversion as well as to subtle variations in the primary sequence. The efficiency of the Tyr to DOPA conversion ranges from a maximum of about 90% to a minimum of 55% in the protein. Trypsin digestion in borate buffer at pH 8 was used to produce DOPA-peptides for sequencing. Notably, trypsin does not cleave Arg/Lys-DOPA sequences at borate concentrations greater than 0.15 M. Peptides with DOPA-containing sequences most frequently have flanking amino acids such as Lys, Ser, or Asp on the N-terminal side and Gly or Asp on the C-terminal side. All protein variants fall within a narrow molecular weight range (30-33 kDa), a pI range of 6.9 to 8.3, and the collective majority would appear to share a common N-terminal sequence up to residue 28. The results suggest some combination of the following: variations in post-translational hydroxylation, alternative post-transcriptional splicing and/or the existence of multiple gene copies of eggshell precursors. The latter have been shown to occur in the blood fluke Schistosoma mansoni [15].
Mol Biochem Parasitol 1992 Sep
PMID:Eggshell precursor proteins of Fasciola hepatica, II. Microheterogeneity in vitelline protein B. 143 55

Crude extracts of hycanthone sensitive Schistosoma mansoni incubated at 37 degrees C in the presence of ATP and Mg2+ induced the covalent binding of tritiated hycanthone (HC) to macromolecules. The same behavior was shown by the HC sensitive species, Schistosoma rodhaini, whereas two independently isolated HC resistant S. mansoni strains had no detectable activity. Sensitive male schistosomes had more activity than females or immature worms. Virtually no activity was present in mouse liver, in human liver, in HeLa cells or in the naturally resistant species Schistosoma japonicum. The activity was destroyed by boiling or by Proteinase K treatment. Covalent binding of tritiated HC to macromolecules could be inhibited by cold HC, oxamniquine or IA-4, while none of the in vitro ineffective analogs, like lucanthone, UK-3883 or 4-desmethyl lucanthone, were inhibitory. These results strongly support the previously advanced suggestion that HC is activated by enzymatic mechanisms which are present only in drug sensitive schistosomes.
Mol Biochem Parasitol 1992 Oct
PMID:Hycanthone resistance in schistosomes correlates with the lack of an enzymatic activity which produces the covalent binding of hycanthone to parasite macromolecules. 143 68

Recombinant phage containing putative Ostertagia ostertagi cysteine protease genes have been isolated from a lambda EMBL-3:genomic DNA library using a Haemonchus contortus cathepsin B-like cysteine protease cDNA as hybridization probe. Restriction enzyme maps of the phages suggest that they identify at least 3 genes, 2 of which appear to be linked in tandem. The complete nucleotide sequence of one gene, CP-1, was determined. The CP-1 gene appears to be organized into 12 exons than span 4.5 kb of DNA. The number and sizes of the exons are essentially identical to those in the H. contortus AC-2 cysteine protease gene. Partial nucleotide sequences obtained for a second O. ostertagi gene, CP-3, revealed a similar organization for exons 8-12 in this gene. Like other cathepsin B-like cysteine proteases, CP-1 appears to be synthesized initially as a preproprotein that is proteolytically processed to its mature form. The amino acid identity between the presumptive CP-1 and CP-3 proteins is 66%, which is similar to the level of homology between the presumed mature protein regions of CP-1 and AC-2. Amino acid identity between CP-1 and AC-2 is greatest in the mature protein region and lowest in the signal sequence and propeptide regions. The CP-3 protein appears to be most closely related to the H. contortus AC-5 protein. CP-1 and CP-3 display significantly greater homology to H. contortus cysteine proteases than they do to human cathepsin B or the Sm31 cysteine protease of Schistosoma mansoni (about 40% identity with each).
Mol Biochem Parasitol 1992 Nov
PMID:Isolation of putative cysteine protease genes of Ostertagia ostertagi. 147

Schistosoma mansoni miracidia in water are known to possess an aerobic energy metabolism, the Krebs cycle being the main terminal of the breakdown of endogenous glycogen reserves. The present study demonstrated that after in vitro transformation of miracidia into sporocysts, the organisms degraded glucose to lactate and carbon dioxide in a more anaerobic ratio than do miracidia. The occurrence of a large Pasteur effect demonstrated, however, that oxidative phosphorylation was still the major process used for energy generation. After 24 h in vitro cultivation the sporocysts had consumed more external glucose and their metabolism had shifted towards lactate production. Sporocysts could cope with inhibited respiration: they had a large anaerobic capacity and survived perfectly in the presence of cyanide, producing a large amount of succinate in addition to lactate. It was demonstrated that this succinate was largely produced via phosphoenolpyruvate carboxykinase (PEPCK). This pathway, which is known to occur in most parasitic helminths, has never been demonstrated in schistosomes, not even in the miracidial stage immediately preceding the sporocysts. It was also shown that in sporocysts part of the lactate was not formed directly by glycolysis, but via a detour including fumarate and the action of PEPCK. The results demonstrated that S. mansoni sporocysts are facultative anaerobes, fully equipped to adjust their energy metabolism to the variable conditions inside their intermediate host, the snail. In the presence of oxygen, they derive most of their energy from the aerobic degradation of glucose to carbon dioxide, but under anaerobic conditions they switch towards lactate and succinate production.
Mol Biochem Parasitol 1992 Nov
PMID:The facultative anaerobic energy metabolism of Schistosoma mansoni sporocysts. 147 1

Schistosomes have a complex life cycle (vertebrate and molluscan hosts as well as larvae living freely in water) in which they are exposed to different environments and temperatures (20 degrees C - 37 degrees C). Since heat shock genes are activated in response to stress and during development [1], it is of interest to study the hsp70 gene family in schistosome. To approach this issue we have isolated from Schistosoma mansoni a genomic clone containing the complete coding region of hsp70 and the 5' flanking DNA with transcription regulatory elements including HSE (heat shock element) sequences.
Mol Biochem Parasitol 1992 Dec
PMID:Cloning and sequencing of an hsp70 gene of Schistosoma mansoni. 148 60

The complete coding DNA for a Schistosoma mansoni homologue of the epidermal growth factor receptor (SER) was characterized from cDNA clones obtained by homology to the tyrosine kinase domain of erbB. The DNA sequence predicts a 200-kDa translation product that contains a secretory leader, a cysteine-rich extracellular domain, a hydrophobic transmembrane sequence, and an intracellular tyrosine kinase domain. The SER transcript is present in cercariae and adult schistosomes. In addition to SER transcripts, schistosomes produce at least 3 variant transcripts encoding truncated SER products that include the secretory leader and a small portion of the extracellular domain followed by short sequences of unrelated, C-terminal amino acids. Based on these sequences, 2 of the variant mRNAs (class 2 and 5) appear to encode soluble, secreted proteins while one (class 4) encodes an SER variant protein with a hydrophobic C-terminus that may serve as a membrane anchor. Class 2 SER variant transcripts are present at levels comparable to SER transcripts in adult worms but are not detected in cercariae. Class 4 and 5 SER variant transcripts are also found within adult worms but at lower levels. Genomic cloning and characterization demonstrate that the variant SER transcripts arise through alternative splicing of the SER gene.
Mol Biochem Parasitol 1992 Jul
PMID:Alternative splicing of the Schistosoma mansoni gene encoding a homologue of epidermal growth factor receptor. 150 37


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