Rogers T.J.,University of Adelaide |
Thorpe C.M.,Tufts New England Medical Center |
Paton A.W.,University of Adelaide |
Paton J.C.,University of Adelaide
Infection and Immunity | Year: 2012
Shiga-toxigenic Escherichia coli (STEC) O113:H21 strains that lack the locus of enterocyte effacement (LEE) efficiently invade eukaryotic cells in vitro, unlike LEE-positive O157:H7 strains. We used a fliC deletion mutant of the O113:H21 STEC strain 98NK2 (98NK2ΔfliC) to show that invasion of colonic epithelial (HCT-8) cells is heavily dependent on production of flagellin, even though adherence to the cells was actually enhanced in the mutant. Flagellin binds and signals through Toll-like receptor 5 (TLR5), but there was no evidence that either TLR5, the adaptor protein myeloid differentiation primary response gene 88 (MyD88), or the serine kinase interleukin-1 receptor-associated kinase (IRAK) were required for invasion of HCT-8 cells by strain 98NK2, as judged by transfection, RNA knockdown, or inhibitor studies. However, pretreatment of cells with anti-asialo-GM1 significantly decreased 98NK2 invasion (by 40.8%), while neuraminidase treatment (which cleaves terminal sialic acid residues, thus converting GM1 into asialo-GM1) significantly increased invasion (by 70.7%). Pretreatment of HCT-8 cells with either the cholesterol-depleting agent methyl-β-cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein significantly decreased invasion by 98NK2, indicating a potential role for lipid rafts in the invasion mechanism. Confocal microscopy also showed invading 98NK2 colocalized with lipid raft markers caveolin-1 and GM1. Interestingly, anti-asialo-GM1, neuraminidase, MβCD, and genistein have similar effects on the vestigial level of STEC invasion seen for STEC strain 98NK2ΔfliC, indicating that lipid rafts mediate a common step in flagellin-dependent and flagellin-independent cellular invasion. © 2012, American Society for Microbiology.
News Article | February 15, 2017
BOCA RATON, Fla.--(BUSINESS WIRE)--Integrated Dermatology Group (IDG), a leading national dermatology practice, has expanded its presence in Virginia with the acquisition of the practice of Dr. Arnold R. Oppenheim, formerly known as Virginia Beach Dermatology Associates, PLLC. Dr. Jonathan Schreiber will serve as Medical Director of the practice, now part of Integrated Dermatology of Tidewater. Dr. Schreiber is the Medical Director of Integrated Dermatology of Tidewater. After graduating with honors from Stanford University, Dr. Schreiber attended Duke University, where he earned both a medical degree and a PhD in Pharmacology. He then completed his internship at Boston Medical Center and his Dermatology residency in Tufts New England Medical Center and Boston Medical Center’s combined program. Dr. Schreiber is a fellow of the American Academy of Dermatology and a member and past president of the Tidewater Dermatology Society. “By partnering with or selling to IDG, the dermatologist can focus on providing high-quality patient care while IDG manages the practice infrastructure and back-office operations, ensuring best clinical practices and patient outcomes,” said Jeff Queen, co-CEO of Integrated Dermatology Group. “For dermatologists who want to monetize all of their practices’ value, IDG has a program allowing them the opportunity to do so. These dermatologists are able to continue practicing dermatology while accruing additional income from the practice,” said Andrew Queen, co-CEO of Integrated Dermatology Group. IDG is continuing a systematic expansion. The Virginia Beach announcement comes on the heels of recent announcements of its partnerships in Chevy Chase, Maryland (Integrated Dermatology of Chevy Chase, LLC) and Boca Raton, Florida (Integrated Dermatology of East Boca, LLC). For more information about one of the nation's largest and fastest growing dermatology groups, with practices located across the country, please contact Integrated Dermatology Group at www.mydermgroup.com or call Jeff Queen at 561-314-2000, extension 1038. Headquartered in Boca Raton, FL, Integrated Dermatology Group is one of the country’s largest providers of dermatology care. The company has expanded its presence nationally by acquiring and partnering with dermatology practices across the United States. This exclusive model allows selling dermatologists to maximize the monetary value of their well-established practice and gives them the choice of either retiring or remaining at the practice indefinitely. Simultaneously, IDG affords dermatologists the unique opportunity of immediately joining an established private practice as a partner, not an employee, with the infrastructure, support, and resources the larger group provides. IDG's mission is to improve the quality of practice life for its dermatologists while adding to their financial success. As part of IDG, dermatologists focus on providing high-quality patient care while IDG removes the stress of day-to-day management by implementing best practices in the areas of compliance, financial services, human resources, payers, and more. For additional information, visit www.mydermgroup.com.
Kestenbaum B.,University of Washington |
Katz R.,University of Washington |
De Boer I.,University of Washington |
Hoofnagle A.,University of Washington |
And 4 more authors.
Journal of the American College of Cardiology | Year: 2011
Objectives: The aim of this study was to evaluate associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately and in combination with incident cardiovascular events and mortality during 14 years of follow-up in the CHS (Cardiovascular Health Study). Background: Vitamin D deficiency and PTH excess are common in older adults and may adversely affect cardiovascular health. Methods: A total of 2,312 participants who were free of cardiovascular disease at baseline were studied. Vitamin D and intact PTH were measured from previously frozen serum using mass spectrometry and a 2-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all-cause mortality. Results: There were 384 participants (17%) with serum 25-OHD concentrations <15 ng/ml and 570 (25%) with serum PTH concentrations <65 pg/ml. After adjustment, each 10 ng/ml lower 25-OHD concentration was associated with a 9% greater (95% confidence interval [CI]: 2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI: 8% to 44% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml were associated with a 29% greater (95% CI: 5% to 55% greater) risk for mortality. Serum PTH concentrations <65 pg/ml were associated with a 30% greater risk for heart failure (95% CI: 6% to 61% greater) but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events. Conclusions: Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways. © 2011 American College of Cardiology Foundation.
Katz E.S.,Childrens Hospital |
Katz E.S.,Harvard University |
D'Ambrosio C.M.,Tufts New England Medical Center
Clinics in Chest Medicine | Year: 2010
Obstructive sleep apnea syndrome (OSAS) is a common and serious cause of metabolic, cardiovascular, and neurocognitive morbidity in children. Children with OSAS have increased upper airway resistance during sleep due to a combination of soft tissue hypertrophy, craniofacial dysmorphology, neuromuscular weakness, or obesity. Consequently, children with OSAS encounter a combination of oxidative stress, inflammation, autonomic activation, and disruption of sleep homeostasis. The threshold amount of OSAS associated with adverse consequences varies widely among children, depending on genetic and environmental factors. The choice of therapy is predicated on the etiology, severity, and natural history of the increased upper airway resistance. © 2010 Elsevier Inc.
Janoff E.N.,University of Colorado at Denver |
Rubins J.B.,University of Minnesota |
Fasching C.,Veterans Affairs Medical Center |
Charboneau D.,University of Minnesota |
And 3 more authors.
Mucosal Immunology | Year: 2014
Bacterial immunoglobulin A1 (IgA1) proteases may sabotage the protective effects of IgA. In vitro, both exogenous and endogenously produced IgA1 protease inhibited phagocytic killing of Streptococcus pneumoniae by capsule-specific IgA1 human monoclonal antibodies (hMAbs) but not IgA2. These IgA1 proteases cleaved and reduced binding of the the effector Fc1 heavy chain but not the antigen-binding F(ab)/light chain to pneumococcal surfaces. In vivo, IgA1 protease-resistant IgA2, but not IgA1 protease-sensitive IgA1, supported 60% survival in mice infected with wild-type S. pneumoniae. IgA1 hMAbs protected mice against IgA1 protease-deficient but not -producing pneumococci. Parallel mouse sera with human IgA2 showed more efficient complement-mediated reductions in pneumococci with neutrophils than did IgA1, particularly with protease-producing organisms. After natural human pneumococcal bacteremia, purified serum IgG inhibited IgA1 protease activity in 7 of 11 patients (64%). These observations provide the first evidence in vivo that IgA1 protease can circumvent killing of S. pneumoniae by human IgA. Acquisition of IgA1 protease-neutralizing IgG after infection directs attention to IgA1 protease both as a determinant of successful colonization and infection and as a potential vaccine candidate. © 2014 Society for Mucosal Immunology.
News Article | October 28, 2016
Imagin Medical is the developer of the ultrasensitive i/Blue Imaging System that will establish a new standard of care for urologists in detecting bladder cancer through endoscopes VANCOUVER, BC and BOSTON, MA--(Marketwired - October 27, 2016) - Imagin Medical ( : IME) ( : IMEXF) ( : DPD2) (the "Company") announced today that Dr. Liam J. Hurley, a member of the Northeast Urologic Surgery, PC, has joined Imagin's Scientific Board of Advisors. Dr. Hurley obtained his Bachelor of Arts degree from Harvard University and his M.D. from Boston University School of Medicine. After spending three years in the U.S. Navy, he completed a General Surgery Residency at St. Elizabeth's Medical Center of Boston and his Urology Residency at the Lahey Clinic in Burlington, MA. He is trained as an adult and pediatric urologist with expertise in genitourinary oncology. Dr. Hurley is a private practice community urologist who has clinical affiliations with Tufts New England Medical Center and Lahey Clinic. Other accomplishments include launching The Boston Urologic Society, serving on the Executive Committee for the Massachusetts Association of Practicing Urologists, and presiding as the Eastern Massachusetts representative to the New England Section of the AUA. Dr. Hurley is Board certified in Urology and is a Fellow of the American College of Surgeons. In 2006, he was chosen as one of Boston's "TOP DOCTORS" by Boston Magazine. "Dr. Hurley's knowledge and expertise in the urology field will be a great asset to our Advisory Board," said Jim Hutchens, Imagin President and CEO. "We look forward to his joining our team as we continue to add relevant expertise to help Imagin succeed." About Imagin Medical Imagin Medical is developing imaging solutions for the early detection of cancer through the use of endoscopes. The Company believes it will radically improve the way physicians detect cancer. Imagin's initial target market is bladder cancer, a major cancer worldwide, the sixth most prevalent in the U.S., and the most costly cancer to treat due to a greater than 50% recurrence rate. Developed at the Lawrence Livermore National Laboratory, this advanced, ultrasensitive imaging technology is based upon improved optical designs and advanced light sensors. Learn more at www.imaginmedical.com. ON BEHALF OF THE BOARD: Information set forth in this news release contains forward-looking statements. These statements reflect management's current estimates, beliefs, intentions and expectations; they are not guarantees of future performance. The Company cautions that all forward-looking statements are inherently uncertain and that actual performance may be affected by a number of material factors, many of which are beyond the Company's control. Accordingly, actual and future events, conditions and results may differ materially from the estimates, beliefs, intentions and expectations expressed or implied in the forward-looking information. Except as required under applicable securities legislation, the Company undertakes no obligation to publicly update or revise forward-looking information. The CSE has neither approved nor disapproved the information contained herein and does not accept responsibility for the adequacy or accuracy of this news release.
Gill J.,University of British Columbia |
Dong J.,University of British Columbia |
Gill J.,Tufts New England Medical Center
Journal of the American Society of Nephrology | Year: 2015
Living kidney donation is declining in the United States. We examined longitudinal trends in living donation as a function of median household income and donor relation to assess the effect of financial barriers on donation in a changing economic environment. The zip code-level median household income of all 71,882 living donors was determined by linkage to the 2000 US Census. Longitudinal changes in the rate of donation were determined in income quintiles between 1999 and 2004, when donations were increasing, and between 2005 and 2010, when donations were declining. Rates were adjusted for population differences in age, sex, race, and ESRD rate using multilevel linear regression models. Between 1999 and 2004, the rate of growth in living donation per million population was directly related to income, increasing progressively from the lowest to highest income quintile, with annualized changes of 0.55 (95% confidence interval [95% CI], 0.14 to 1.05) for Q1 and 1.77 (95% CI, 0.66 to 2.77) for Q5 ( P<0.05). Between 2005 and 2010, donation declined in Q1, Q2, and Q3; was stable in Q4; and continued to grow in Q5. Longitudinal changes varied by donor relationship, and the association of income with longitudinal changes also varied by donor relationship. In conclusion, changes in living donation in the past decade varied by median household income, resulting in increased disparities in donation between low- and high-income populations. These findings may inform public policies to support living donation during periods of economic volatility. Copyright © 2015 by the American Society of Nephrology.
Gill J.,University of British Columbia |
Dong J.,University of British Columbia |
Rose C.,University of British Columbia |
Johnston O.,University of British Columbia |
And 2 more authors.
Journal of the American Society of Nephrology | Year: 2013
Studies of racial disparities in access to living donor kidney transplantation focus mainly on patient factors, whereas donor factors remain largely unexamined. Here, data from the US Census Bureau were combined with data on all African-American and white living kidney donors in the United States who were registered in the United Network for Organ Sharing (UNOS) between 1998 and 2010 (N=57,896) to examine the associations between living kidney donation (LKD) and donor median household income and race. The relative incidence of LKD was determined in zip code quintiles ranked by median household income after adjustment for age, sex, ESRD rate, and geography. The incidence of LKD was greater in higher-income quintiles in both African-American and white populations. Notably, the total incidence of LKD was higherin the African-American population than in the white population (incidence rate ratio [IRR], 1.20; 95% confidence interval [95% CI], 1.17 to 1.24]), but ratios varied by income. The incidence of LKD was lower in the African-American population than in the white population in the lowest income quintile (IRR, 0.84; 95% CI, 0.78 to 0.90), but higher in the African-American population in the three highest income quintiles, with IRRs of 1.31 (95% CI, 1.22 to 1.41) in Q3, 1.50 (95% CI, 1.39 to 1.62) in Q4, and 1.87 (95% CI, 1.73 to 2.02) in Q5. Thus, these data suggest that racial disparities in access to living donor transplantation are likely due to socioeconomic factors rather than cultural differences in the acceptance of LKD. Copyright © 2013 by the American Society of Nephrology.
Francis J.H.,Sloan Kettering Cancer Center |
Kleinerman R.A.,U.S. National Institutes of Health |
Seddon J.M.,Tufts New England Medical Center |
Abramson D.H.,Sloan Kettering Cancer Center
Gynecologic Oncology | Year: 2012
Objective: In the US, second non-ocular malignancies are the primary cause of death in retinoblastoma survivors with the germline RB1 mutation. Soft tissue sarcomas are one of the most likely malignancies to pose a risk to these patients, with leiomyosarcoma (LMS) being the most common subtype. As our cohort is followed for a longer period, we discover new second malignancy risks for these patients. Methods: We estimated the risk for uterine leiomyosarcoma (ULMS) in a cohort of 1854 patients with retinoblastoma who were diagnosed at two US institutions from 1914 through 1996. The standardized incidence ratio and excess absolute risk were calculated by comparison with population data from the Connecticut Tumor Registry or from National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. The cumulative risk at 50 years of age was also calculated. Results: Seven of 525 female hereditary retinoblastoma patients developed ULMS. Five of these patients were used in the risk analysis, resulting in an excess risk of 3.87 per 10,000 women. Among hereditary patients who developed ULMS the excess risk increases dramatically with age: to 20/10,000 for female hereditary retinoblastoma patients aged between 30 and 39 years, and to 27/10,000 for patients aged 40 + years. Conclusion: There is a substantial excess risk of ULMS in female hereditary retinoblastoma patients. As more patients survive into their thirties, this number is likely to increase. These findings raise the question of early childbearing, screening and prophylactic measures in hereditary retinoblastoma patients: all issues that would benefit from confirmation from other retinoblastoma cohorts, to allow for better guided counsel of these patients. © 2011 Elsevier Inc. All rights reserved.
Delcommenne M.,Rush University Medical Center |
Klingemann H.-G.,Tufts New England Medical Center
Human Antibodies | Year: 2012
This study was undertaken to generate human single chain variable antibody fragments (scFvs) reacting specifically against multiple myeloma (MM) cells using the phage display technique. To isolate myeloma-specific scFvs, we used a simple subtractive strategy by adsorbing the Griffin #1 antibody phage library against myeloma cells in the presence of excess decoy biotinylated HL60 cells, and then removing the unwanted decoy cells using streptavidin coated plates. From eleven scFvs that were isolated, two antibodies, D4A4 and D6B10 stained MM cell lines and patient MM cells with higher intensity than normal plasma cells. Both D4A4 and D6B10 scFvs immunoprecipitated syndecan-1 from myeloma cells and recognized sulfated motifs on syndecan-1-associated heparan sulfate (HS) chains. ScFv D4A4 competed with D6B10 for binding to MM cells. However, they differed in their fine specificities. ScFv D6B10 recognized HS 2,6-O-, N-sulfated motifs and, in contrast, binding of scFv D4A4 required N-sulfation combined with either 2-O- or 6-O-sulfation. Increased D6B10 binding on MM cells suggests that their HS chains contain a greater number of 2,6-O-, N-sulfated motifs than normal plasma cells. Since these highly sulfated motifs bind various angiogenic and growth factors and present them to their respective receptors, they could be instrumental for MM cell survival, proliferation and metastasis. Therefore, scFvs D4A4 and D6B10 provide a means to easily monitor changes in sulfation patterns of heparan sulfate during myeloma tumor progression. © 2012 - IOS Press and the authors. All rights reserved.