An 85-kDa Group VI phospholipase A 2 enzyme (iPLA 2 ) that does not require Ca 2؉ for catalysis has recently been cloned from three rodent species. A homologous 88-kDa enzyme has been cloned from human B-lymphocyte lines that contains a 54-amino acid insert not present in the rodent enzymes, but human cells have not previously been observed to express catalytically active iPLA 2 isoforms other than the 88-kDa protein. We have cloned cDNA species that encode two distinct iPLA 2 isoforms from human pancreatic islet RNA and a human insulinoma cDNA library. One isoform is an 85-kDa protein (short isoform of human iPLA 2 (SH-iPLA 2 )) and the other an 88-kDa protein (long isoform of human iPLA 2 (LH-iPLA 2 )). Transcripts encoding both isoforms are also observed in human promonocytic U937 cells. Recombinant SH-iPLA 2 and LH-iPLA 2 are both catalytically active in the absence of Ca 2؉ and inhibited by a bromoenol lactone suicide substrate, but LH-iPLA 2 is activated by ATP, whereas SH-iPLA 2 is not. The human iPLA 2 gene has been found to reside on chromosome 22 in region q13.1 and to contain 16 exons represented in the LH-iPLA 2 transcript. Exon 8 is not represented in the SH-iPLA 2 transcript, indicating that it arises by an exon-skipping mechanism of alternative splicing. The amino acid sequence encoded by exon 8 of the human iPLA 2 gene is proline-rich and shares a consensus motif of PX 5 PX 8 HHPX 12 NX 4 Q with the proline-rich middle linker domains of the Smad proteins DAF-3 and Smad4.
Intravitreally injected ranibizumab and aflibercept have similar half-lives in aqueous humor and shorter half-lives in vitrectomized eyes. Compared to IVR, IVA suppresses VEGF level for a longer time period.
The use of a large number of cardiovascular biomarkers, meant to complement the use of the electrocardiogram, echocardiography cardiac imaging, and clinical symptom assessment, has become a routine in clinical diagnosis, differential diagnosis, risk stratification, and prognosis and guides the management of patients with suspected cardiovascular diseases. There is a broad consensus that cardiac troponin and natriuretic peptides are the preferred biomarkers in clinical practice for the diagnosis of the acute coronary syndrome and heart failure, respectively, while the roles and possible clinical applications of several other potential biomarkers are still under study. This review mainly focuses on the recent studies of the roles and clinical applications of troponin and natriuretic peptides, which seem to be the best-validated markers in distinguishing and predicting the future cardiac events of patients with suspected cardiovascular diseases. Additionally, the review briefly discusses some of the large number of potential markers that may play a more prominent role in the future.
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