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New insights into the families of PLC enzymes: looking back and going forward.

ABSTRACT: A study in this issue of the Biochemical Journal by Harden and colleagues, in association with one published in the Biochemical Journal very recently [Hwang, Oh, Shin, Kim, Ryu and Suh (2005) Biochem. J. 389, 181-186], have defined a new member of the superfamily of PLC (phosphoinositide-specific phospholipase C) enzymes, PLCeta. Two isoforms, PLCeta1 and PLCeta2, and their splice variants add to the molecular diversity of PLC enzymes. The studies of PLCeta regulation suggest that at least some splice variants of PLCeta2 could be regulated by the G-protein subunits Gbetagamma. As two other families, PLCbeta and PLC, are also regulated through heterotrimeric G-proteins, this finding reveals further complexity and possible interplay between different PLC families and their regulatory networks. At this point, when it is likely that the PLCeta family completes the effort of identifying new members of this related group of PLC enzymes, I also discuss some more general concepts of PLC regulation and catalysis, and challenges awaiting their further studies.

SUBMITTER: Katan M

PROVIDER: S-EPMC1276975 | biostudies-other | 2005 Nov

REPOSITORIES: biostudies-other

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Project description:Recent studies have found substantial variation in hospital resource use by expired Medicare beneficiaries with chronic illnesses. By analyzing only expired patients, these studies cannot identify differences across hospitals in health outcomes like mortality. This study examines the association between mortality and resource use at the hospital level, when all Medicare beneficiaries hospitalized for heart failure are examined.A total of 3999 individuals hospitalized with a principal diagnosis of heart failure at 6 California teaching hospitals between January 1, 2001, and June 30, 2005, were analyzed with multivariate risk-adjustment models for total hospital days, total hospital direct costs, and mortality within 180-days after initial admission ("Looking Forward"). A subset of 1639 individuals who died during the study period were analyzed with multivariate risk-adjustment models for total hospital days and total hospital direct costs within 180-days before death ("Looking Back"). "Looking Forward" risk-adjusted hospital means ranged from 17.0% to 26.0% for mortality, 7.8 to 14.9 days for total hospital days, and 0.66 to 1.30 times the mean value for indexed total direct costs. Spearman rank correlation coefficients were -0.68 between mortality and hospital days, and -0.93 between mortality and indexed total direct costs. "Looking Back" risk-adjusted hospital means ranged from 9.1 to 21.7 days for total hospital days and 0.91 to 1.79 times the mean value for indexed total direct costs. Variation in resource use site ranks between expired and all individuals were attributable to insignificant differences.California teaching hospitals that used more resources caring for patients hospitalized for heart failure had lower mortality rates. Focusing only on expired individuals may overlook mortality variation as well as associations between greater resource use and lower mortality. Reporting values without identifying significant differences may result in incorrect assumption of true differences.

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New insights into the families of PLC enzymes: looking back and going forward.

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