No abstract

Background-The production of collagen is fundamental to atherosclerosis and critically dependent on posttranslational modification by prolyl 4-hydroxylase. Methods and Results-We report the cloning of a novel prolyl 4-hydroxylase catalytic (␣) subunit from human vascular smooth muscle cells. The peptide displayed conservation of critical residues for interacting with Fe 2ϩ and 2-oxoglutarate, essential cosubstrates for prolyl 4-hydroxylase activity. Furthermore, when the recombinant protein was expressed in cells, it associated with the ␤-subunit of prolyl 4-hydroxylase and could catalyze prolyl 4-hydroxylation of a collagen-like peptide. The tissue distribution was dissimilar from that of the 2 previously cloned ␣-subunits, suggesting a role beyond redundancy. Importantly, the novel gene was expressed in the fibrous cap of human carotid atherosclerotic lesions. Conclusions-The discovery of a novel prolyl 4-hydroxylase ␣-subunit, here termed the ␣(III)-subunit, suggests a new participant in collagen synthesis that, in view of the expression findings, may be relevant to atherosclerotic disease.

In the rodent uterus, prostaglandin E(2) (PGE(2)) is believed to have a major role in implantation and decidualization. The present study investigated the temporal and hormonal control of mRNA expression for the four E-prostanoid (EP(1-4)) receptors in the rat endometrium. For Northern blot analysis and in situ hybridization, samples were obtained from rats on Days 1-10 of pseudopregnancy or from rats differentially sensitized for the decidual cell reaction with estradiol. No EP(1) mRNA signal was detected. Endometrial EP(2) and EP(3) mRNA levels increased to a maximum on Day 5, and the mRNAs were localized to the luminal epithelium at the antimesometrial pole, and in the endometrial stroma and glandular epithelium, respectively. Endometrial EP(4) mRNA levels were unchanged on Days 1-5, but the mRNA was concentrated in the antimesometrial endometrial stroma on Day 5. Cell-specific expression of EP(2), EP(3), and EP(4) on Day 5 was dependent upon a dose of estradiol given on Day 4 that induced differential uterine sensitization on Day 5. After the application of a deciduogenic stimulus on Day 5, mRNA levels for these receptors decreased significantly, while in nonstimulated horns they remained elevated. Overall, these results support a role for PGE(2) in the onset of receptivity and initiation of decidualization in the rat.

Continuous acid-suppressive therapy, prokinetic therapy and total parenteral nutrition. Repetitive endoscopic polypectomy (also known as debulking) was performed twice and was followed by gastrectomy with duodenoesophageal anastomosis.