Functional evaluation of the role of C-type lectin domain family 16A at the chromosome 16p13 locus

Abstract The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, allowing not only a morphologic but also a functional evaluation of the hepatobiliary system. The mechanism of uptake and excretion of gadoxetic acid via transporters, such as organic anion transporting polypeptides (OATP1,3), multidrug resistance-associated protein 2 (MRP2) and MRP3, has been elucidated in the literature. Furthermore, GA uptake can be estimated on either static images or on dynamic imaging, for example, the hepatic extraction fraction (HEF) and liver perfusion. GA-enhanced MRI has achieved an important role in evaluating morphology and function in chronic liver diseases (CLD), allowing to distinguish between the two subgroups of nonalcoholic fatty liver diseases (NAFLD), simple steatosis and nonalcoholic steatohepatitis (NASH), and help to stage fibrosis and cirrhosis, predict liver transplant graft survival, and preoperatively evaluate the risk of liver failure if major resection is planned. Finally, because of its noninvasive nature, GA-enhanced MRI can be used for long-term follow-up and post-treatment monitoring. This review article aims to describe the current role of GA-enhanced MRI in quantifying liver function in a variety of hepatobiliary disorders.

Download Full-text

Morphologic and functional evaluation by CT-scan volumetric assessment and renal scintigraphy after nephron sparing surgery. Which role of the surgical complexity on the postoperative outcome?

European Urology Supplements ◽

10.1016/s1569-9056(18)33259-7 ◽

2018 ◽

Vol 17 (8) ◽

pp. 283

Author(s):

C. Fiori ◽

D. Amparore ◽

M. Manfredi ◽

D. Garrou ◽

G. Cattaneo ◽

...

Keyword(s):

Ct Scan ◽

Postoperative Outcome ◽

Nephron Sparing Surgery ◽

Renal Scintigraphy ◽

Functional Evaluation ◽

Volumetric Assessment ◽

Nephron Sparing ◽

Surgical Complexity

Download Full-text

Complete Removal of N-Linked Glycans from Platelet GPIbα Impairs Platelet Agglutination and von Willebrand Factor Binding In Vitro.

Blood ◽

10.1182/blood.v108.11.1535.1535 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1535-1535

Author(s):

Suzana M. Zorca ◽

Emma C. Josefsson ◽

Viktoria Rumjantseva ◽

John H. Hartwig ◽

Karin M. Hoffmeister

Keyword(s):

Flow Cytometry ◽

Von Willebrand Factor ◽

Cho Cells ◽

Chinese Hamster ◽

Surface Expression ◽

Lectin Domain ◽

Von Willebrand ◽

Willebrand Factor

Abstract We previously reported that the lectin domain of the αMβ2 receptor on macrophages mediates the rapid clearance of transfused washed murine platelets which have been refrigerated for 2 hrs in the absence of plasma. The clearance is mediated by the recognition of exposed βN-acetylglucosamine (β-GlcNAc) residues on N-linked glycans of clustered platelet GPIbα molecules. Covering the exposed β-GlcNAc residues on GPIbα N-linked glycans via galactosylation prevents the clearance of chilled murine platelets from the circulation. The role of N-linked glycans in platelet function and survival is unclear. To dissect the role of N-linked glycosylation of GPIbα on the binding of von Willebrand factor (vWf), we use human platelets and Chinese Hamster Ovary (CHO) cells, stably expressing human GPIbα/βand GPIX. Deglycosylation of platelet GPIbα N-liked glycans was achieved using the enzyme peptide-N-glycosidase F (PGNaseF), specific for complex N-linked glycans. In agglutination assays using platelets incubated with and without PNGaseF for 16hrs at 37°C, we observed 30-40 % less agglutination in response to ristocetin for platelets depleted of N-linked glycans with PNGaseF. Additionally, a 30 % reduction in vWf binding to PNGaseF-treated platelets compared with control platelets was measured by flow cytometry, using a FITC-conjugated mAb that detects surface-bound vWf. In CHO cells, GPIbα N-linked oligosaccharides were manipulated by adding swainsonine or tunicamycin, two inhibitors of N-linked oligosaccharide synthesis in the Golgi. vWf binding to platelets or to CHO cells was studied by aggregometry or by light microscopy to establish the fraction of CHO-cell aggregates. As was the case with platelets, vWf-dependent aggregation of CHO cells expressing GPIb-IX decreased three fold in response to botrocetin, but only following complete N-linked glycans depletion with tunicamycin. In contrast, partial N-linked carbohydrate modification with swainsonine did not significantly alter aggregate formation in CHO- cells expressing GPIb-IX. Complete inhibition of N-linked glycosylation decreased botrocetin-induced vWf binding to CHO- cells expressing GPIb-IX by ~50%, as determined by flow cytometry. No change was observed following swainsonine treatment. Surface expression of GP1bα remained unchanged after both tunicamycin and swainsonine treatment, and with PGNaseF treatment of platelets. These results confirm that 1) N-linked glycans are not required for GPIbα surface expression, and 2) indicate that N-linked glycans likely play a role in vWf binding to platelet GPIbα.

Download Full-text