7 research outputs found
Regulation of [Ca2+]c oscillations by plasma membrane Ca2+ fluxes: a role for natriuretic peptides
Elevated serum gastrin is associated with melanoma progression: putative role in increased migration and invasion of melanoma cells
Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study
Objective: To examine the association of maternal caffeine intake with fetal growth restriction.
Design Prospective longitudinal observational study.
Setting: Two large UK hospital maternity units.
Participants: 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy.
Investigations: Quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Smoking and alcohol were assessed by self reported status and by measuring salivary cotinine concentrations.
Main outcome measures: Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations.
Results: Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction (odds ratios 1.2 (95% CI 0.9 to 1.6) for 100-199 mg/day, 1.5 (1.1 to 2.1) for 200-299 mg/day, and 1.4 (1.0 to 2.0) for >300 mg/day compared with <100 mg/day; test for trend P<0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster compared to a slower caffeine clearance (test for interaction, P=0.06).
Conclusions: Caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy
Clinical, histologic and quantitative angiographic predictors of restenosis after directional coronary atherectomy: a multivariate analysis of the renarrowing process and late outcome
OBJECTIVES. To characterize predictors of restenosis after successful directional atherectomy, we reviewed the clinical, angiographic and procedural data obtained during 132 consecutive procedures. METHODS. Clinical and angiographic follow-up data were obtained in a prospectively collected and consecutive series of 125 patients who underwent 132 atherectomy procedures for de novo (89%) or restenotic (11%) lesions in native coronary arteries. Restenosis was assessed clinically and by quantitative coronary angiography. A dual approach to data analysis was taken to gain insight into factors affecting the clinical outcome and vessel wall healing response. Therefore, multivariate analysis was performed to 1) determine the correlates of residual lumen diameter at follow-up (angiographic outcome), and 2) characterize the determinants of the late lumen loss (renarrowing process). RESULTS. Clinical and angiographic follow-up data after successful atherectomy were obtained in 100% and 95%, respectively. Atherectomy achieved an acute lumen gain of 1.28 +/- 0.48 mm (mean +/- SD), resulting in a minimal lumen diameter of 2.44 +/- 0.47 mm. At follow-up, the minimal lumen diameter decreased to 1.78 +/- 0.64 mm. The angiographic restenosis rate was 28% if the traditional 50% stenosis cutoff criterion was applied. Larger vessel size and postatherectomy minimal lumen diameter and right coronary or left circumflex artery lesions were independent predictors of a larger minimal lumen diameter (angiographic outcome). Lumen loss during follow-up (renarrowing process) was independently predicted by relative lumen gain and preprocedural minimal lumen diameter. CONCLUS
Role of Adaptor Complex AP-3 in Targeting Wild-Type and Mutated CD63 to Lysosomes
CD63 is a lysosomal membrane protein that belongs to the tetraspanin family. Its carboxyterminal cytoplasmic tail sequence contains the lysosomal targeting motif GYEVM. Strong, tyrosine-dependent interaction of the wild-type carboxyterminal tail of CD63 with the AP-3 adaptor subunit μ3 was observed using a yeast two-hybrid system. The strength of interaction of mutated tail sequences with μ3 correlated with the degree of lysosomal localization of similarly mutated human CD63 molecules in stably transfected normal rat kidney cells. Mutated CD63 containing the cytosolic tail sequence GYEVI, which interacted strongly with μ3 but not at all with μ2 in the yeast two-hybrid system, localized to lysosomes in transfected normal rat kidney and NIH-3T3 cells. In contrast, it localized to the cell surface in transfected cells of pearl and mocha mice, which have genetic defects in genes encoding subunits of AP-3, but to lysosomes in functionally rescued mocha cells expressing the δ subunit of AP-3. Thus, AP-3 is absolutely required for the delivery of this mutated CD63 to lysosomes. Using this AP-3–dependent mutant of CD63, we have shown that AP-3 functions in membrane traffic from the trans-Golgi network to lysosomes via an intracellular route that appears to bypass early endosomes