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Oh D.-J.,Massachusetts Eye and Ear Infirmary | Kang M.H.,Massachusetts Eye and Ear Infirmary | Ooi Y.H.,New York Downtown Hospital | Choi K.R.,Ewha Womans University | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2013

PURPOSE. Intraocular pressure (IOP) regulation is largely unknown. SPARC-null mice demonstrate a lower IOP resulting from increased outflow. SPARC is a matricellular protein often associated with fibrosis. We hypothesized that SPARC overexpression would alter IOP by affecting extracellular matrix (ECM) synthesis and/or turnover in the trabecular meshwork (TM). METHODS. An adenoviral vector containing human SPARC was used to increase SPARC expression in human TM endothelial cells and perfused human anterior segments using multiplicities of infection (MOIs) 25 or 50. Total RNA from TM was used for quantitative PCR, while protein from cell lysates and conditioned media were used for immunoblot analyses and zymography. After completion of perfusion, the anterior segments were fixed, sectioned, and examined by light and confocal microscopy. RESULTS. SPARC overexpression increased the IOP of perfused human anterior segments. Fibronectin and collagens IV and I protein levels were elevated in both TM cell cultures and within the juxtacanalicular (JCT) region of perfused anterior segments. Collagen VI and laminin protein levels were increased in TM cell cultures but not in perfused anterior segments. The protein levels of pro-MMP-9 decreased while the kinetic inhibitors of metalloproteinases, TIMP-1 and PAI-1 protein levels, increased at MOI 25. At MOI 50, the protein levels of pro-MMP-1, -3, and -9 also decreased while PAI-1 and TIMP-1 and -3 increased. Only MMP-9 activity was decreased on zymography. mRNA levels of the collagens, fibronectin, and laminin were not affected by SPARC overexpression. CONCLUSIONS. SPARC overexpression increases IOP in perfused cadaveric human anterior segments resulting from a qualitative change the JCT ECM. Selective decrease of MMP-9 activity is likely part of the mechanism. SPARC is a regulatory node for IOP. © 2013 The Association for Research in Vision and Ophthalmology, Inc. Source

Walker M.D.,Columbia University | Liu X.S.,Columbia University | Liu X.S.,University of Pennsylvania | Zhou B.,University of Amsterdam | And 5 more authors.
Journal of Bone and Mineral Research | Year: 2013

Compared to white women, premenopausal Chinese-American women have more plate-like trabecular (Tb) bone. It is unclear whether these findings are relevant to postmenopausal women and if there are racial differences in the deterioration of bone microarchitecture with aging. We applied individual trabecula segmentation and finite element analysis to high-resolution peripheral quantitative computed tomography images in premenopausal and postmenopausal Chinese-American and white women to quantify within-race age-related differences in Tb plate-versus-rod microarchitecture and bone stiffness. Race-menopause status interactions were assessed. Comparisons between races within menopause status were adjusted for age, height and weight. Comparisons between premenopausal and postmenopausal women were adjusted for height and weight. Adjusted analyses at the radius indicated that premenopausal Chinese-Americans had a higher plate bone volume fraction (pBV/TV), Tb plate-to-rod ratio (P-R ratio), and greater plate-plate junction densities (P-P Junc.D) versus white women (all p < 0.01), resulting in 27% higher Tb stiffness (p < 0.05). Greater cortical thickness and density (Ct.Th and Dcort) and more Tb plates led to 19% greater whole bone stiffness (p < 0.05). Postmenopausal Chinese-Americans had similar pBV/TV and P-P Junc.D, yet a higher P-R ratio versus white women. Postmenopausal Chinese-American versus white women had greater Ct.Th, Dcort, and relatively intact Tb plates, resulting in similar Tb stiffness but 12% greater whole bone stiffness (p < 0.05). In both races, Ct.Th and Dcort were lower in postmenopausal versus premenopausal women and there were no differences between races. Tb plate parameters were also lower in postmenopausal versus premenopausal women, but age-related differences in pBV/TV, P-R ratio, and P-P Junc D were greater (p < 0.05) in Chinese-Americans versus white women. There are advantages in cortical and Tb bone in premenopausal Chinese-American women. Within-race cross-sectional differences between premenopausal and postmenopausal women suggest greater loss of plate-like Tb bone with aging in Chinese-Americans, though thicker cortices and more plate-like Tb bone persists. Copyright © 2013 American Society for Bone and Mineral Research. Source

Uppal R.,New York Downtown Hospital | Charles E.,Cornell University | Lake-Bakaar G.,Cornell University
Journal of Clinical Virology | Year: 2010

The nature of the B-cell subsets associated with chronic hepatitis C virus related type II mixed cryoglobulinemia (HCV-MC) is unclear. We report the case of a 64-year-male with acute onset wrist drop and foot drop, secondary to HCV-MC related mononeuritis multiplex, who was treated with rituximab, an anti-CD20+ antibody directed against B cells. We monitored the frequency of B-cell subsets in peripheral blood before and after rituximab, and correlated B-cell subset changes with clinical response. Significant improvements in his wrist and foot drop, as well as his vasculitic rash, depression and erectile dysfunction were evident within six days of starting rituximab and have persisted several months after B-cell recovery. More than 95% of CD20+ B cells had disappeared from peripheral blood within 1 week, returning to baseline by week 21. CD20+CXCR3+ frequency at baseline was similar to that at week 21. CD20+CD5+, the human equivalent of B1 B cells and CD20+IgM+IgD+, naïve B cells were increased. By contrast, CD20+CD27+ memory cell frequency was reduced. These data suggest that CD27+ memory B cells, but not CD5+ and IgM+IgD+ B cells may play a role in the clinical manifestations of cryoglobulinemia. © 2009 Elsevier B.V. All rights reserved. Source

Lin R.Y.,New York Downtown Hospital | Lin R.Y.,New York Medical College | Levine R.J.,New York Medical College | Lin H.,McGill University
Allergy and Asthma Proceedings | Year: 2013

Since angiotensin-converting enzyme (ACE) inhibitors became common treatments, there have been increasing reports of angioedema (AE). AE hospitalization (AEH) trend data in the new millennium are limited. This study calculates hospitalization rates for AEs and describes clinical characteristics of AEHs in the United States, especially as related to specific adverse drug effects (ADEs). The National Inpatient Samples 2000-2009 were queried for AEHs to calculate hospitalization rates and to examine for associations with specified ADEs, certain comorbidities, and demographic features. AEHs requiring intubation or tracheostomy were also examined for associations. There was a significant increase in the AEH rates (3.4 per 105 to 5.4 per 105) over the study period (p < 0.0001) and the hospitalization rates for African Americans (AAs) were consistently higher. Throughout the study the proportions of AEH coding any ADEs, or an ADE due to a cardiovascular (CV) or antihypertensive (aHTN) drug increased over time. By 2009, 61.7% AEHs coded an ADE. Of these, 58.7% were caused by CV or aHTN drugs. In AEHs, having an ADE from a CV or aHTN medication had the strongest adjusted associations with hypertension and renal disease as well as with alcohol-related disorders. In AEHs, intubation/ tracheostomy had the strongest ADE associations related to CV or aHTN medication (adjusted odds ratio, 1.4; 95% CI, 1.3, 1.6). AEHs continue to increase, but this can only be partially attributed to ACE inhibitor usage. Intubation/tracheostomy appears to be greater in AEHs with ADE due to CV/aHTN drugs. Alcohol-related disorders may have a role in ACE inhibitor-associated AEH. Copyright © 2013, OceanSide Publications, Inc., U.S.A. Source

Liu X.S.,Columbia University | Walker M.D.,Columbia University | McMahon D.J.,Columbia University | Udesky J.,Columbia University | And 3 more authors.
Journal of Bone and Mineral Research | Year: 2011

Despite lower areal bone mineral density (aBMD), Chinese-American women have fewer fractures than white women. We hypothesized that better skeletal microstructure in Chinese-American women in part could account for this paradox. Individual trabecula segmentation (ITS), a novel image-analysis technique, and micro-finite-element analysis (μFEA) were applied to high-resolution peripheral quantitative computed tomography (HR-pQCT) images to determine bone microarchitecture and strength in premenopausal Chinese-American and white women. Chinese-American women had 95% and 80% higher plate bone volume fraction at the distal radius and tibia, respectively, as well as 20% and 18% higher plate number density compared with white women (p<.001). With similar rodlike characteristics, the plate-to-rod ratio was twice as high in the Chinese-American than in white trabecular bone (p<.001). Plate-rod junction density, a parameter indicating trabecular network connections, was 37% and 29% greater at the distal radius and tibia, respectively, in Chinese-American women (p<.002). Moreover, the orientation of the trabecular bone network was more axially aligned in Chinese-American women because axial bone volume fraction was 51% and 32% higher at the distal radius and tibia, respectively, than in white women (p<.001). These striking differences in trabecular bone microstructure translated into 55% to 68% (distal radius, p<.001) and 29% to 43% (distal tibia, p<.01) greater trabecular bone strength, as assessed by Young's moduli, in the Chinese-American versus the white group. The observation that Chinese-American women have a major microstructural advantage over white women may help to explain why their risk of fracture is lower despite their lower BMD. Copyright © 2011 American Society for Bone and Mineral Research. Source

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