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Padilla N.,Aix - Marseille University | Maraninchi M.,Aix - Marseille University | Beliard S.,Aix - Marseille University | Berthet B.,AP HM | And 11 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

Objective - The dyslipidemia of obesity and other insulin-resistant states is characterized by the elevation of plasma triglyceride-rich lipoproteins (TRL) of both hepatic (apoB-100-containing very low-density lipoprotein) and intestinal (apoB-48-containing chylomicrons) origin. Bariatric surgery is a well-established and effective modality for the treatment of obesity and is associated with improvements in several metabolic abnormalities associated with obesity, including a reduction in plasma triglycerides. Here, we have investigated the effect of bariatric surgery on TRL metabolism.Approach and Results - Twenty-two nondiabetic, obese subjects undergoing bariatric surgery: sleeve gastrectomy (n=12) or gastric bypass (n=10) were studied. Each subject underwent 1 lipoprotein turnover study 1 month before surgery followed by a second study, 6 months after surgery, using established stable isotope enrichment methodology, in constant fed state. TRL-apoB-100 concentration was significantly reduced after sleeve gastrectomy, explained by a decrease (P<0.05) in TRL-apoB-100 production rate and an increase (P<0.05) in TRL-apoB-100 fractional catabolic rate. TRLapoB- 48 concentration was also significantly reduced after sleeve gastrectomy, explained by reduction in TRL-apoB-48 production rate (P<0.05). For gastric bypass, although TRL-apoB-100 concentration declined after surgery (P<0.01), without a significant decline in TRL-apoB-48, there was no significant change in either TRL-apoB-100 or TRL-apoB-48 production rate or fractional catabolic rate. The reduction in TRL-apoB-100 concentration was significantly associated with a reduction in plasma apoC-III in the pooled group of patients undergoing bariatric surgery.Conclusions - This is the first human lipoprotein kinetic study to explore the mechanism of improvement of TRL metabolism after bariatric surgery. These effects may contribute to the decrease of cardiovascular mortality after surgery. © 2014 American Heart Association, Inc.

Gray E.J.,University of TorontoOntario | Gray E.J.,Sinai University | Gray E.J.,Center for Addiction and Mental Health Hospital | Petsalaki E.,Sinai University | And 10 more authors.
Journal of Biological Chemistry | Year: 2014

SH2D5 is a mammalian-specific, uncharacterized adaptorlike protein that contains an N-terminal phosphotyrosine-binding domain and a C-terminal Src homology 2 (SH2) domain.We show that SH2D5 is highly enriched in adult mouse brain, particularly in Purkinjie cells in the cerebellum and the cornu ammonis of the hippocampus. Despite harboring two potential phosphotyrosine (Tyr(P)) recognition domains, SH2D5 binds minimally to Tyr(P) ligands, consistent with the absence of a conserved Tyr(P)-binding arginine residue in the SH2 domain. Immunoprecipitation coupled to mass spectrometry (IP-MS) from cultured cells revealed a prominent association of SH2D5 with breakpoint cluster region protein, a RacGAP that is also highly expressed in brain. This interaction occurred between the phosphotyrosine-binding domain of SH2D5 and an NxxF motif located within the N-terminal region of the breakpoint cluster region. siRNA-mediated depletion of SH2D5 in a neuroblastoma cell line, B35, induced a cell rounding phenotype correlated with low levels of activated Rac1-GTP, suggesting that SH2D5 affects Rac1-GTP levels. Taken together, our data provide the first characterization of the SH2D5 signaling protein. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Ng E.,Sunnybrook Health science Center | Ng E.,University of TorontoOntario | Schurr P.,Sunnybrook Health science Center | Reilly M.,Sunnybrook Health science Center | And 4 more authors.
Early Human Development | Year: 2016

Background In preterm infants, it is unknown whether feeding affects neural breathing pattern. Objectives By measuring the diaphragm electrical activity (Edi) waveform, we evaluated the effect of enteral feeding and compared the effects of feeding methods on neural breathing pattern and central apnea in very low birth weight preterm infants. Methods In a prospective, randomized, crossover study, ten non-ventilated preterm infants with birth weights < 1250 g and tolerating full feeds were randomized to either bolus feeding (BF) or slow infusion feeding (SF) over 90 min, followed by crossover to the other method at the next feed. Edi was continuously measured by a feeding catheter with miniaturized sensors. Five 15-min epochs were chosen [Baseline (BL), first 15 min and 90 min after BF/SF started] for breath-by-breath analyses of neural breathing pattern, including Edi peak, Edi min (end-expiratory), neural inspiratory and expiratory times, neural respiratory rate, and central apnea. Primary outcome was change in Edi min with feed. Secondary outcomes include change in Edi peak, frequency and duration of central apnea with feeding. Results Although intrasubject coefficient of variation was not significantly different, individual responses to feeding and feeding method were variable. No significant difference in Edi timing, Edi min, Edi peak, or apnea was observed for the different epochs. Conclusions In this study cohort, neural breathing pattern does not appear to be consistently affected by enteral feeding or the feeding method. Compared with BF, SF does not appear to reduce the number or duration of apneas. © 2016 Elsevier Ireland Ltd

Blackmore K.M.,Lunenfeld Tanenbaum Research Institute | Blackmore K.M.,University of TorontoOntario | Knight J.A.,Lunenfeld Tanenbaum Research Institute | Walter J.,University of TorontoOntario | Lilge L.,University of TorontoOntario
PLoS ONE | Year: 2015

Mammographic density (MD), associated with higher water and lower fat content in the breast, is strongly related to breast cancer risk. Optical attenuation spectroscopy (OS) is a non-imaging method of evaluating breast tissue composition by red and near-infrared light transmitted through the breast that, unlike mammography, does not involve radiation. OS provides information on wavelength dependent light scattering of tissue and on absorption by water, lipid, oxy-, deoxy-hemoglobin. We propose that OS could be an alternative marker of breast cancer risk and that OS breast tissue measures will be associated with MD. In the present analysis, we developed an algorithm to estimate breast tissue composition and light scattering parameters using a spectrally constrained global fitting procedure employing a diffuse light transport model. OS measurements were obtained from 202 pre- and post-menopausal women with normal mammograms. Percent density (PD) and dense area (DA) were measured using Cumulus. The association between OS tissue composition and PD and DA was analyzed using linear regression adjusted for body mass index. Among pre-menopausal women, lipid content was significantly inversely associated with square root transformed PD (β = -0.05, p = 0.0002) and DA (β = -0.05, p = 0.019); water content was significantly positively associated with PD (β = 0.06, p = 0.008). Tissue oxygen saturation was marginally inversely associated with PD (β = -0.03, p = 0.057) but significantly inversely associated with DA (β = -0.10, p = 0.002). Among post-menopausal women lipid and water content were significantly associated (negatively and positively, respectively) with PD (βlipid = -0.08, βwater = 0.14, both p<0.0001) and DA (βlipid = -0.10, p<0.0001; βwater = 0.11, p = 0.001). The association between OS breast content and PD and DA is consistent with more proliferation in dense tissue of younger women, greater lipid content in low density tissue and higher water content in high density tissue. OS may be useful for assessing physiologic tissue differences related to breast cancer risk, particularly when mammography is not feasible or easily accessible. © 2015 Blackmore et al.

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