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https://www.readbyqxmd.com/read/28882819/cardiomyocyte-specific-telomere-shortening-is-a-distinct-signature-of-heart-failure-in-humans
#1
Maryam Sharifi-Sanjani, Nicholas M Oyster, Elisia D Tichy, Kenneth C Bedi, Ofer Harel, Kenneth B Margulies, Foteini Mourkioti
BACKGROUND: Telomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by the disease in human hearts is not yet identified. The aim of this study was to systematically evaluate the cell type specificity of telomere shortening in patients with heart failure in relation to their cardiac disease, age, and sex. METHODS AND RESULTS: We studied cardiac tissues from patients with heart failure by utilizing telomere quantitative fluorescence in situ hybridization, a highly sensitive method with single-cell resolution...
September 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28768909/addressing-metabolic-heterogeneity-in-clear-cell-renal-cell-carcinoma-with-quantitative-dixon-mri
#2
Yue Zhang, Durga Udayakumar, Ling Cai, Zeping Hu, Payal Kapur, Eun-Young Kho, Andrea Pavía-Jiménez, Michael Fulkerson, Alberto Diaz de Leon, Qing Yuan, Ivan E Dimitrov, Takeshi Yokoo, Jin Ye, Matthew A Mitsche, Hyeonwoo Kim, Jeffrey G McDonald, Yin Xi, Ananth J Madhuranthakam, Durgesh K Dwivedi, Robert E Lenkinski, Jeffrey A Cadeddu, Vitaly Margulis, James Brugarolas, Ralph J DeBerardinis, Ivan Pedrosa
BACKGROUND: Dysregulated lipid and glucose metabolism in clear cell renal cell carcinoma (ccRCC) has been implicated in disease progression, and whole tumor tissue-based assessment of these changes is challenged by the tumor heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations in the whole tumor. METHODS: We applied Dixon-based MRI for in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted regions of interest of 45 primary ccRCCs and correlated these MRI measures to mass spectrometry-based lipidomics and metabolomics of anatomically colocalized tissue samples isolated from the same tumor after surgery...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28756575/evaluating-the-safety-of-medication-exposures-during-pregnancy-a-case-study-of-study-designs-and-data-sources-in-multiple-sclerosis
#3
Whitney S Krueger, Mary S Anthony, Catherine W Saltus, Andrea V Margulis, Elena Rivero-Ferrer, Brigitta Monz, Ceri Hirst, David Wormser, Elizabeth Andrews
BACKGROUND: Regulatory agencies often request prospective, product-specific post-authorization pregnancy exposure registries to monitor safety during pregnancy, even though studies using existing health databases could also be employed. OBJECTIVES: Using multiple sclerosis (MS) as a case study, we evaluated various study designs and data sources previously used to study medication exposure in pregnancy. METHODS: We examined (1) strengths and limitations of study designs used for pregnancy safety studies in women exposed to MS-specific medications during pregnancy and (2) existing data sources used to conduct such studies in other disease areas...
July 29, 2017: Drugs—Real World Outcomes
https://www.readbyqxmd.com/read/28717236/high-performance-micro-flow-cytometer-based-on-optical-fibres
#4
S Etcheverry, A Faridi, H Ramachandraiah, T Kumar, W Margulis, F Laurell, A Russom
Flow cytometry is currently the gold standard for analysis of cells in the medical laboratory and biomedical research. Fuelled by the need of point-of-care diagnosis, a significant effort has been made to miniaturize and reduce cost of flow cytometers. However, despite recent advances, current microsystems remain less versatile and much slower than their large-scale counterparts. In this work, an all-silica fibre microflow cytometer is presented that measures fluorescence and scattering from particles and cells...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709887/frequency-and-prognostic-value-of-pten-loss-in-patients-with-upper-tract-urothelial-carcinoma-treated-with-radical-nephroureterectomy
#5
Malte Rieken, Shahrokh F Shariat, Jose A Karam, Beat Foerster, Francesca Khani, Kilian Gust, Mohammad Abufaraj, Christopher G Wood, Alon Z Weizer, Jay D Raman, Charles C Guo, Nathalie Rioux-Leclercq, Andrea Haitel, Karim Bensalah, Yair Lotan, Alexander Bachmann, Angelo M De Marzo, Brian D Robinson, Vitaly Margulis
PURPOSE: To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. MATERIALS AND METHODS: We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions...
July 12, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28694147/predictive-and-prognostic-value-of-preoperative-thrombocytosis-in-upper-tract-urothelial-carcinoma
#6
Beat Foerster, Marco Moschini, Mohammad Abufaraj, Francesco Soria, Kilian M Gust, Morgan Rouprêt, Pierre I Karakiewicz, Alberto Briganti, Michael Rink, Luis Kluth, Romain Mathieu, Vitaly Margulis, Yair Lotan, Atiqullah Aziz, Hubert John, Shahrokh F Shariat
PURPOSE: The purpose of this study was to evaluate the predictive and prognostic role of preoperative thrombocytosis (TC) in upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) in a large multi-institutional cohort of patients. METHODS: Records of 2492 patients undergoing RNU for non-metastatic UTUC between 1990 and 2008 were retrospectively analyzed. Preoperative TC was defined as a platelet count > 400 × 10(9)/L, irrespective of gender type...
June 19, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28668287/prognostic-value-of-pd-1-and-pd-l1-expression-in-patients-with-high-grade-upper-tract-urothelial-carcinoma
#7
Laura-Maria Krabbe, Barbara Heitplatz, Sina Preuss, Ryan C Hutchinson, Solomon L Woldu, Nirmish Singla, Martin Boegemann, Christopher G Wood, Jose A Karam, Alon Z Weizer, Jay D Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Leonid M Rapoport, Peter V Glybochko, Marco Roscigno, Christian Bolenz, Karim Bensalah, Arthur I Sagalowsky, Shahrokh F Shariat, Yair Lotan, Evanguelos Xylinas, Vitaly Margulis
PURPOSE: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry...
June 28, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28559794/possible-function-of-molecular-chaperones-in-diseases-caused-by-propagating-amyloid-aggregates
#8
REVIEW
Vladimir F Lazarev, Elena R Mikhaylova, Irina V Guzhova, Boris A Margulis
The vast majority of neurodegenerative pathologies stem from the formation of toxic oligomers and aggregates composed of wrongly folded proteins. These protein complexes can be released from pathogenic cells and enthralled by other cells, causing the formation of new aggregates in a prion-like manner. By this mechanism, migrating complexes can transmit a disorder to distant regions of the brain and promote gradually transmitting degenerative processes. Molecular chaperones can counteract the toxicity of misfolded proteins...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28450110/a-hydrocortisone-derivative-binds-to-gapdh-and-reduces-the-toxicity-of-extracellular-polyglutamine-containing-aggregates
#9
Vladimir F Lazarev, Elena R Mikhaylova, Elizaveta A Dutysheva, Roman V Suezov, Irina V Guzhova, Boris A Margulis
Huntington's disease (HD) has been recently shown to have a horizontally transmitted, prion-like pathology. Thus, the migration of polyglutamine-containing aggregates to acceptor cells is important for the progression of HD. These aggregates contain glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which increases their intracellular transport and their toxicity. Here, we show that RX624, a derivative of hydrocortisone that binds to GAPDH, prevents the formation of aggregates of GAPDH-polyglutamine excreted into the culture medium by PC-12 rat cells expressing mutant huntingtin...
April 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28442383/the-utility-of-axial-abdominal-imaging-after-partial-nephrectomy-for-t1-renal-cell-carcinoma-surveillance
#10
Igor Sorokin, Noah E Canvasser, Vitaly Margulis, Yair Lotan, Ganesh Raj, Arthur Sagalowsky, Jeffrey C Gahan, Jeffrey A Cadeddu
PURPOSE: The overall recurrence rate of T1 renal cell carcinoma is low. We evaluated abdominal imaging after partial nephrectomy based on current guidelines for T1 renal cell carcinoma surveillance. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with T1 renal cell carcinoma who underwent partial nephrectomy between 2006 and 2012 followed by abdominal imaging at our institution. Primary and secondary outcomes were the incidence and timing, respectively, of imaging diagnosed abdominal recurrences...
April 23, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28370075/cancer-incidence-after-initiation-of-antimuscarinic-medications-for-overactive-bladder-in-the-united-kingdom-evidence-for-protopathic-bias
#11
James A Kaye, Andrea V Margulis, Joan Fortuny, Lisa J McQuay, Estel Plana, Jennifer L Bartsch, Christine L Bui, Susana Perez-Gutthann, Alejandro Arana
STUDY OBJECTIVE: To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs). DESIGN: Retrospective cohort study. DATA SOURCE: United Kingdom's Clinical Practice Research Datalink. PATIENTS: A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOABs-darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium-between January 2004 and December 2012...
June 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28331342/spotlight-on-atezolizumab-and-its-potential-in-the-treatment-of-advanced-urothelial-bladder-cancer
#12
REVIEW
Ahmet Murat Aydin, Solomon L Woldu, Ryan C Hutchinson, Martin Boegemann, Aditya Bagrodia, Yair Lotan, Vitaly Margulis, Laura-Maria Krabbe
Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28199780/cytomegalovirus-responsive-cd8-t-cells-expand-after-solid-organ-transplantation-in-the-absence-of-cmv-disease
#13
L E Higdon, J Trofe-Clark, S Liu, K B Margulies, M K Sahoo, E Blumberg, B A Pinsky, J S Maltzman
Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid organ transplant recipients. Approximately 60% of adults are CMV seropositive, indicating previous exposure. Following resolution of the primary infection, CMV remains in a latent state. Reactivation is controlled by memory T cells in healthy individuals; transplant recipients have reduced memory T cell function due to chronic immunosuppressive therapies. In this study, CD8(+) T cell responses to CMV polypeptides immediate-early-1 and pp65 were analyzed in 16 CMV-seropositive kidney and heart transplant recipients longitudinally pretransplantation and posttransplantation...
August 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28191886/sirtuin-1-regulates-cardiac-electrical-activity-by-deacetylating-the-cardiac-sodium-channel
#14
Ajit Vikram, Christopher M Lewarchik, Jin-Young Yoon, Asma Naqvi, Santosh Kumar, Gina M Morgan, Julia S Jacobs, Qiuxia Li, Young-Rae Kim, Modar Kassan, Jing Liu, Mohanad Gabani, Ajay Kumar, Haider Mehdi, Xiaodong Zhu, Xiaoqun Guan, William Kutschke, Xiaoming Zhang, Ryan L Boudreau, Shengchuan Dai, Daniel S Matasic, Saet-Byel Jung, Kenneth B Margulies, Vikas Kumar, Markus M Bachschmid, Barry London, Kaikobad Irani
The voltage-gated cardiac Na(+) channel (Nav1.5), encoded by the SCN5A gene, conducts the inward depolarizing cardiac Na(+) current (INa) and is vital for normal cardiac electrical activity. Inherited loss-of-function mutations in SCN5A lead to defects in the generation and conduction of the cardiac electrical impulse and are associated with various arrhythmia phenotypes. Here we show that sirtuin 1 deacetylase (Sirt1) deacetylates Nav1.5 at lysine 1479 (K1479) and stimulates INa via lysine-deacetylation-mediated trafficking of Nav1...
March 2017: Nature Medicine
https://www.readbyqxmd.com/read/28191289/renal-cell-carcinoma-metastatic-to-the-scalp
#15
Mounir Errami, Vitali Margulis, Sergio Huerta
Because of the asymptomatic natural history of renal cell carcinoma (RCC), by the time a diagnosis is made, metastatic disease is present in about one third of the cases. Thus, the overall survival of patients with RCC remains poor. Ultimately up to 50% of patients with RCC will develop metastases. Metastatic lesions from RCC are usually observed in the lungs, liver or bone. Metastases to the brain or the skin from RCC are rare. Here we present a patient diagnosed with RCC, found to have no evidence of metastases at the time of nephrectomy, who presented two years later with metastases to the scalp...
November 17, 2016: Rare Tumors
https://www.readbyqxmd.com/read/28104715/detailed-echocardiographic-phenotyping-in-breast-cancer-patients-associations-with-ejection-fraction-decline-recovery-and-heart-failure-symptoms-over-3-years-of-follow-up
#16
Hari K Narayan, Brian Finkelman, Benjamin French, Theodore Plappert, David Hyman, Amanda M Smith, Kenneth B Margulies, Bonnie Ky
BACKGROUND: Cardiovascular disease in patients with breast cancer is of growing concern. The longitudinal effects of commonly used therapies, including doxorubicin and trastuzumab, on cardiac remodeling and function remain unknown in this population. We aimed to define the changes in echocardiographic parameters of structure, function, and ventricular-arterial coupling, and their associations with left ventricular ejection fraction (LVEF) and heart failure symptoms. METHODS: In a longitudinal prospective cohort study of 277 breast cancer participants receiving doxorubicin (Dox), trastuzumab (Tras), or both (Dox+Tras), we obtained 1249 echocardiograms over a median follow-up of 2...
April 11, 2017: Circulation
https://www.readbyqxmd.com/read/28075543/prognostic-value-of-tissue-based-biomarker-signature-in-clear-cell-renal-cell-carcinoma
#17
Ahmed Q Haddad, Jun-Hang Luo, Laura-Maria Krabbe, Oussama Darwish, Bishoy Gayed, Ramy Youssef, Payal Kapur, Dinesh Rakheja, Yair Lotan, Arthur Sagalowsky, Vitaly Margulis
OBJECTIVE: To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence...
May 2017: BJU International
https://www.readbyqxmd.com/read/27887951/a-multi-institutional-comparison-of-clinicopathological-characteristics-and-oncologic-outcomes-of-upper-tract-urothelial-carcinoma-in-china-and-the-united-states
#18
Nirmish Singla, Dong Fang, Xiaohong Su, Zhengqing Bao, Zhenpeng Cao, Syed M Jafri, Gengyan Xiong, Lei Zhang, Ryan Hutchinson, Arthur Sagalowsky, Yair Lotan, Xuesong Li, Liqun Zhou, Jay D Raman, Vitaly Margulis
PURPOSE: We evaluated differences in clinicopathological characteristics and oncologic outcomes between patients with upper tract urothelial carcinoma in mainland China and the United States. MATERIALS AND METHODS: We retrospectively compiled clinicopathological and oncologic outcomes data on patients with upper tract urothelial carcinoma treated surgically at tertiary care medical facilities in the United States or China from 1998 to 2015. Baseline demographics, comorbidities and pathological features were evaluated...
May 2017: Journal of Urology
https://www.readbyqxmd.com/read/27830374/prognostic-role-of-expression-of-n-cadherin-in-patients-with-upper-tract-urothelial-carcinoma-a-multi-institutional-study
#19
Mohammad Abufaraj, Marco Moschini, Francesco Soria, Kilian Gust, Mehmet Özsoy, Romain Mathieu, Morgan Rouprêt, Vitaly Margulis, Jose A Karam, Christopher G Wood, Alberto Briganti, Karim Bensalah, Andrea Haitel, Shahrokh F Shariat
PURPOSE: To assess the role of N-cadherin as prognostic biomarker in patients with upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. PATIENTS AND METHODS: Immunohistochemistry was used to evaluate the status of N-cadherin expression in 678 patients with unilateral sporadic UTUC treated with radical nephroureterectomy. N-cadherin was considered positive if any immunoreactivity with membranous staining was detected. The Kaplan-Meier method was used to estimate recurrence-free survival, overall survival and cancer-specific survival...
July 2017: World Journal of Urology
https://www.readbyqxmd.com/read/27813284/functional-connectivity-alterations-in-patients-with-chronic-hepatitis-c-virus-infection-a-multimodal-mri-study
#20
S Kharabian Masouleh, S Herzig, L Klose, E Roggenhofer, H Tenckhoff, T Kaiser, A Thöne-Otto, M Wiese, T Berg, M L Schroeter, D S Margulies, A Villringer
Chronic hepatitis C virus (HCV) infection is associated with fatigue and depression. Cognitive impairments are also reported in a smaller number of HCV-positive patients. Recent studies linked HCV to low-grade inflammation in brain. Here, we test the hypothesis that chronic HCV is associated with 3T-neuroimaging-derived grey matter volume (GMV) and functional connectivity alterations in a sample of chronic HCV (1b), without severe liver disease. Regional GMV and resting-state fMRI-derived eigenvector centrality (EC) were compared between 19 HCV-positive patients and 23 healthy controls (all females, 50-69 and 52-64 years, respectively), controlling for white matter hyperintensities and age...
March 2017: Journal of Viral Hepatitis
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