Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.5.5 (CPS)
 1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma filtration characteristics of three hollow fiber plasma separation filters (Plasmaflo Hi-05, Extraplex BL 550 and CPS-10) were studied in a single-needle setting by means of the double headpump. Plasma exchange was carried out in 12 patients during a total number of 59 sessions. For each filter, a mean total ultrafiltration volume of +/- 3,000 ml was obtained over a period from 92 to 121 min. The lowest and highest obtained mean filtration flows were 26.7 +/- 2.5 and 36.6 +/- 1.7 ml/min for Extraplex BL 550 and CPS-10, respectively (p less than 0.01). The pre- and postplasmapheresis pressures, measured in the bubble trap chamber as an indirect estimation of transmembrane pressure, were lower for the Plasmaflo Hi-05 than for the two other filters under study; pressures remained unaltered during the session. Blood pressure showed a minor but significant decline during plasmapheresis with the Plasmaflo filter. A reduction after plasmapheresis by more than 40% of the immunoglobulins IgE, IgG, IgM and IgA, and of complement factors C3 and C4 was seen for each of the filters and no significant differences between the filters were observed. An additional study on 6 filters with constant blood flow and TMP showed minor differences in the transmembrane pressure necessary to obtain a given filtration volume per unit of time and similar sieving coefficients for immunoglobulins. This study demonstrates that with this single-needle technique a satisfying immunoglobulin extraction performance was obtained for each of the filter types studied; however, there existed minor but significant differences in the patient hemodynamic status according to the membrane used.
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PMID:Single-needle membrane plasmapheresis. In vivo comparison of plasma separator performances. 339 73

New treatments need to be developed for the significant human diseases of toxoplasmosis and malaria to circumvent problems with current treatments and drug resistance. Apicomplexan parasites causing these lethal diseases are deficient in pyrimidine salvage, suggesting that selective inhibition of de novo pyrimidine biosynthesis can lead to a severe loss of uridine 5'-monophosphate (UMP) and thymidine 5'-monophosphate (dTMP) pools, thereby inhibiting parasite RNA and DNA synthesis. Disruption of Toxoplasma gondii carbamoyl phosphate synthetase II (CPSII) induces a severe uracil auxotrophy with no detectable parasite replication in vitro and complete attenuation of virulence in mice. Here we show that a CPSII cDNA minigene efficiently complements the uracil auxotrophy of CPSII-deficient mutants, restoring parasite growth and virulence. Our complementation assays reveal that engineered mutations within, or proximal to, the catalytic triad of the N-terminal glutamine amidotransferase (GATase) domain inactivate the complementation activity of T. gondii CPSII and demonstrate a critical dependence on the apicomplexan CPSII GATase domain in vivo. Surprisingly, indels present within the T. gondii CPSII GATase domain as well as the C-terminal allosteric regulatory domain are found to be essential. In addition, several mutations directed at residues implicated in allosteric regulation in Escherichia coli CPS either abolish or markedly suppress complementation and further define the functional importance of the allosteric regulatory region. Collectively, these findings identify novel features of T. gondii CPSII as potential parasite-selective targets for drug development.
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PMID:Genetic identification of essential indels and domains in carbamoyl phosphate synthetase II of Toxoplasma gondii. 1899 49