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Discovery And Development Of Human Monoclonal Antibodies To Block Rhd Alloimmunization During Pregnancy, Tushar Gupta, Melissa Gawron, Colby A. Souders, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean McCauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini 2016 University of Massachusetts Medical School

Discovery And Development Of Human Monoclonal Antibodies To Block Rhd Alloimmunization During Pregnancy, Tushar Gupta, Melissa Gawron, Colby A. Souders, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean Mccauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini

UMass Center for Clinical and Translational Science Research Retreat

Exposure of an Rh negative mother to red blood cells (RBCs) of an Rh positive fetus results in alloimmunization and development of anti-RhD antibodies. The anti-RhD antibodies cause hemolytic disease of the new born babies during subsequent pregnancies. Current prophylactic treatment involves polyclonal anti-RhD IgG purified from plasma of humans and is administered in approximately 20% of pregnancies. While the current prophylaxis is effective, it involves the use of human plasma and non-RhD specific antibodies, thus posing a risk of transmitting infections and undesired antibody reactions. Moreover, there is a serious scarcity of plasma donors to meet the requirement of ...


The Mysteries Of Your Blood, Alexandra J. Mauer 2016 Butler University

The Mysteries Of Your Blood, Alexandra J. Mauer

BU Well

Did you know that your blood type can be useful for determining disease susceptibility and even creating a diet that works best for your personal metabolism? The Mysteries of your Blood is an article that delves into the science behind the ABO blood types and explains why your body can handle certain foods, stress, and illness differently than someone with a different blood type. It proposes a new, perplexing way to determine how to avoid certain health problems while at the same time offering suggestions of what to eat or, rather, what to avoid eating.


To What Extent Did Blood Transfusion Systems And Technologies Modernize During World War Ii?, Hannah J. LeBlanc 2016 Sunset High School

To What Extent Did Blood Transfusion Systems And Technologies Modernize During World War Ii?, Hannah J. Leblanc

Young Historians Conference

This investigation will explore changes in blood transfusion during World War II (1939-1945). Medical technology and collection systems for whole blood and blood plasma in particular will be examined. The focus of this investigation will be the United States, but Great Britain will also be mentioned due to its close blood transfusion-related interactions with the United States during this period. Additionally, blood transfusion prior to World War II and in modern times will also be considered in this investigation to provide context and to allow assessment of modernization during the war. However, artificial blood substitutes will not be considered, nor ...


Primary Malignant Pleural Effusion With A Profound Type B Lactic Acidosis, Rachel Kinney DO, Christine Saraceni DO, Eliot L. Friedman MD 2016 Lehigh Valley Health Network

Primary Malignant Pleural Effusion With A Profound Type B Lactic Acidosis, Rachel Kinney Do, Christine Saraceni Do, Eliot L. Friedman Md

Department of Medicine

No abstract provided.


A Case Report Of Ruxolitinib Induced Hypocalcemia: A Stochastic Or Deterministic Effect?, Arsha Sreedhar MD, Ranjit R. Nair MD, Gretchen A. Perilli MD 2016 Lehigh Valley Health Network

A Case Report Of Ruxolitinib Induced Hypocalcemia: A Stochastic Or Deterministic Effect?, Arsha Sreedhar Md, Ranjit R. Nair Md, Gretchen A. Perilli Md

Department of Medicine

No abstract provided.


A Case-Control Genome-Wide Association Study Identifies Genetic Modifiers Of Fetal Hemoglobin In Sickle Cell Disease., Li Liu, Alexander Pertsemlidis, Liang-Hao Ding, Michael D Story, Martin H Steinberg, Paola Sebastiani, Carolyn Hoppe, Samir K. Ballas, Betty S Pace 2016 University of Texas at Dallas

A Case-Control Genome-Wide Association Study Identifies Genetic Modifiers Of Fetal Hemoglobin In Sickle Cell Disease., Li Liu, Alexander Pertsemlidis, Liang-Hao Ding, Michael D Story, Martin H Steinberg, Paola Sebastiani, Carolyn Hoppe, Samir K. Ballas, Betty S Pace

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is a group of inherited blood disorders that have in common a mutation in the sixth codon of the β-globin (HBB) gene on chromosome 11. However, people with the same genetic mutation display a wide range of clinical phenotypes. Fetal hemoglobin (HbF) expression is an important genetic modifier of SCD complications leading to milder symptoms and improved long-term survival. Therefore, we performed a genome-wide association study (GWAS) using a case-control experimental design in 244 African Americans with SCD to discover genetic factors associated with HbF expression. The case group consisted of subjects with HbF≥8.6 ...


Trends In Survival Of Chronic Lymphocytic Leukemia Patients In Germany And The Usa In The First Decade Of The Twenty-First Century., Dianne Pulte, Felipe A Castro, Lina Jansen, Sabine Luttmann, Bernd Holleczek, Alice Nennecke, Meike Ressing, Alexander Katalinic, Hermann Brenner 2016 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ); Cardeza Foundation, Division of Hematology, Department of Medicine, Thomas Jefferson University

Trends In Survival Of Chronic Lymphocytic Leukemia Patients In Germany And The Usa In The First Decade Of The Twenty-First Century., Dianne Pulte, Felipe A Castro, Lina Jansen, Sabine Luttmann, Bernd Holleczek, Alice Nennecke, Meike Ressing, Alexander Katalinic, Hermann Brenner

Cardeza Foundation for Hematologic Research

BACKGROUND: Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997-2011.

METHODS: Data were extracted from 12 cancer registries in Germany and compared to the data from the USA. Period analysis was used to estimate 5- and 10-year relative survival (RS).

RESULTS: Five- and 10-year RS estimates in 2009-2011 of 80.2 and 59.5%, respectively, in Germany and 82.4 and 64.7%, respectively ...


Principles Of Medical Oncology, James Liebmann, Richard S. Pieters 2016 University of Massachusetts Medical School

Principles Of Medical Oncology, James Liebmann, Richard S. Pieters

Cancer Concepts: A Guidebook for the Non-Oncologist

Medical oncologists are internists specializing in the care of the adult cancer patient. They frequently function as a primary care physician for patients with cancer. This chapter in Cancer Concepts: A Guidebook for the Non-Oncologist will review the practice of medical oncology and some general principles followed in the use of chemotherapy. Concepts including goals of chemotherapy treatment, evaluation of the effects of chemotherapy, integration of chemotherapy with other cancer treatments, and use of combinations of chemotherapy drugs will be covered.


Novel Oral Transforming Growth Factor-Beta Signaling Inhibitor Ew-7197 Eradicates Cml-Initiating Cells, Kazuhito Naka, Shaoguang Li, Dae-Kee Kim 2016 Kanazawa University

Novel Oral Transforming Growth Factor-Beta Signaling Inhibitor Ew-7197 Eradicates Cml-Initiating Cells, Kazuhito Naka, Shaoguang Li, Dae-Kee Kim

Open Access Articles

Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia-initiating cells (CML-LICs). However, little is known about the therapeutic benefits such CML-LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW-7197, an orally bioavailable transforming growth factor-beta signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML-LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW-7197 to CML-affected mice significantly delayed disease ...


Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L.C. Luban, Jeffery L Miller, Ross M. Fasano, Emily Riehm Meier 2016 George Washington University

Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L.C. Luban, Jeffery L Miller, Ross M. Fasano, Emily Riehm Meier

Pediatrics Faculty Publications

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly ...


Reduction Of Oxidative Stress And Storage Lesions (Rcsl) In Red Blood Cells - Analysis Of Ascorbic Acid (Aa), N-Acetylcysteine Amide (Ad4), And Serotonin (5-Ht), Shanmuka Gadiraju 2016 Virginia Commonwealth University

Reduction Of Oxidative Stress And Storage Lesions (Rcsl) In Red Blood Cells - Analysis Of Ascorbic Acid (Aa), N-Acetylcysteine Amide (Ad4), And Serotonin (5-Ht), Shanmuka Gadiraju

Undergraduate Research Posters

Oxidative stress is a common occurrence in red blood cell (RBC) storage in blood banks throughout the world. Typically RBC units stored under routine standard protocol (stored in SAGM-CPD additive solution) can only be kept up to 42 days for transfusion usage before being discarded. I am studying the effects of Ascorbic Acid (AA), N-acetylcysteine amide (AD4), and Serotonin (5-HT) as additives in blood bank storage because I want to find out if these additives can reduce storage-induced oxidative stress on red blood cells (RBCs), in order to help my reader understand how potential blood storage additives can affect the ...


Kras Codon 12 And 13 Mutations In Relation To Disease-Freesurvival In Braf-Wild-Type Stage Iii Colon Cancers From An Adjuvant Chemotherapytrial (N0147 Alliance)., Harry H Yoon, David Tougeron, Qian Shi, Steven R Alberts, Michelle R Mahoney, Garth D Nelson, Suresh Nair, Stephen N Thibodeau, Richard M Goldberg, Daniel J Sargent, Frank A Sinicrope 2015 Lehigh Valley Health Network

Kras Codon 12 And 13 Mutations In Relation To Disease-Freesurvival In Braf-Wild-Type Stage Iii Colon Cancers From An Adjuvant Chemotherapytrial (N0147 Alliance)., Harry H Yoon, David Tougeron, Qian Shi, Steven R Alberts, Michelle R Mahoney, Garth D Nelson, Suresh Nair, Stephen N Thibodeau, Richard M Goldberg, Daniel J Sargent, Frank A Sinicrope

Suresh G. Nair MD

PURPOSE: We examined the prognostic impact of specific KRAS mutations in patients with stage III colon adenocarcinoma receiving adjuvant FOLFOX alone or combined with cetuximab in a phase III trial (N0147). Analysis was restricted to BRAF-wild-type tumors, because BRAF mutation was associated with poor prognosis, and BRAF and KRAS mutations are mutually exclusive.

EXPERIMENTAL DESIGN: The seven most common KRAS mutations in codon 12 and codon 13 were examined in 2,478 BRAF-wild-type tumors. Because KRAS mutations in codon 12 (n = 779) or 13 (n = 220) were not predictive of adjuvant cetuximab benefit, study arms were pooled for analysis. Disease-free ...


Comparison Of Folfiri With Or Without Cetuximab In Patients With Resected Stage Iii Colon Cancer; Ncctg (Alliance) Intergroup Trial N0147, J Huang, Suresh Nair, M Mahoney, G Nelson, A Shields, E Chan, R Goldberg, S Gill, M Kahlenberg, J Quesenberry, S Thibodeau, T Smyrk, A Grothey, F Sinicrope, T Webb, G Farr, B Pockaj, J Berenberg, M Mooney, D Sargent, S Alberts 2015 Mayo Clinic Rochester

Comparison Of Folfiri With Or Without Cetuximab In Patients With Resected Stage Iii Colon Cancer; Ncctg (Alliance) Intergroup Trial N0147, J Huang, Suresh Nair, M Mahoney, G Nelson, A Shields, E Chan, R Goldberg, S Gill, M Kahlenberg, J Quesenberry, S Thibodeau, T Smyrk, A Grothey, F Sinicrope, T Webb, G Farr, B Pockaj, J Berenberg, M Mooney, D Sargent, S Alberts

Suresh G. Nair MD

Background: Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. Patients and Methods: After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival ...


Can Surgeons Improve Survival In Stage Iv Melanoma?, Paul Mosca, Erik Teicher, Suresh Nair, Barbara Pockaj 2015 Lehigh Valley Health Network

Can Surgeons Improve Survival In Stage Iv Melanoma?, Paul Mosca, Erik Teicher, Suresh Nair, Barbara Pockaj

Suresh G. Nair MD

Successful systemic management of stage IV melanoma continues to be elusive because of the paucity of effective therapies. This has fueled the continued interest in surgical resection. Several single-institution studies and a current, large, multi-institutional phase III trial have demonstrated a survival benefit for patients who underwent surgical resection for melanoma metastases. Incorporating these results into new approaches using multimodality treatment may enhance survival in patients with stage IV melanoma.


Hypoxia Induces Phenotypic Plasticity And Therapy Resistance In Melanoma Via The Tyrosine Kinase Receptors Ror1 And Ror2, Michael O'Connell, Katie Marchbank, Marie Webster, Alexander Valiga, Amanpreet Kaur, Adina Vultur, Ling Li, Meenhard Herlyn, Jessie Villanueva, Qin Liu, Xiangfan Yin, Sandy Widura, Janelle Nelson, Nivia Ruiz, Tura C Camilli, Fred E Indig, Keith T Flaherty, Jennifer A Wargo, Dennie T Frederick, Zachary A Cooper, Suresh Nair, Ravi K Amaravadi, Lynn M Schuchter, Giorgos C Karakousis, Wei Xu, Xiaowei Xu, Ashani T Weeraratna 2015 The Wistar Institute

Hypoxia Induces Phenotypic Plasticity And Therapy Resistance In Melanoma Via The Tyrosine Kinase Receptors Ror1 And Ror2, Michael O'Connell, Katie Marchbank, Marie Webster, Alexander Valiga, Amanpreet Kaur, Adina Vultur, Ling Li, Meenhard Herlyn, Jessie Villanueva, Qin Liu, Xiangfan Yin, Sandy Widura, Janelle Nelson, Nivia Ruiz, Tura C Camilli, Fred E Indig, Keith T Flaherty, Jennifer A Wargo, Dennie T Frederick, Zachary A Cooper, Suresh Nair, Ravi K Amaravadi, Lynn M Schuchter, Giorgos C Karakousis, Wei Xu, Xiaowei Xu, Ashani T Weeraratna

Suresh G. Nair MD

An emerging concept in melanoma biology is that of dynamic, adaptive phenotype switching, where cells switch from a highly proliferative, poorly invasive phenotype to a highly invasive, less proliferative one. This switch may hold significant implications not just for metastasis, but also for therapy resistance. We demonstrate that phenotype switching and subsequent resistance can be guided by changes in expression of receptors involved in the noncanonical Wnt5A signaling pathway, ROR1 and ROR2. ROR1 and ROR2 are inversely expressed in melanomas and negatively regulate each other. Furthermore, hypoxia initiates a shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype. Notably ...


Patient And Tumor Characteristics And Braf And Kras Mutations In Coloncancer, Ncctg/Alliance N0147., Wilson I Gonsalves, Michelle R Mahoney, Daniel J Sargent, Garth D Nelson, Steven R Alberts, Frank A Sinicrope, Richard M Goldberg, Paul J Limburg, Stephen N Thibodeau, Axel Grothey, Joleen M Hubbard, Emily Chan, Suresh Nair, Jeffrey L Berenberg, Robert R McWilliams 2015 Division of Hematology/Division of Medical Oncology

Patient And Tumor Characteristics And Braf And Kras Mutations In Coloncancer, Ncctg/Alliance N0147., Wilson I Gonsalves, Michelle R Mahoney, Daniel J Sargent, Garth D Nelson, Steven R Alberts, Frank A Sinicrope, Richard M Goldberg, Paul J Limburg, Stephen N Thibodeau, Axel Grothey, Joleen M Hubbard, Emily Chan, Suresh Nair, Jeffrey L Berenberg, Robert R Mcwilliams

Suresh G. Nair MD

BACKGROUND: KRAS and BRAF (V600E) mutations are important predictive and prognostic markers, respectively, in colon cancer, but little is known about patient and clinical factors associated with them.

METHODS: Two thousand three hundred twenty-six of 3397 patients in the N0147 phase III adjuvant trial for stage III colon cancer completed a patient questionnaire. Primary tumors were assessed for KRAS and BRAF (V600E) mutations and defective mismatch repair (dMMR) status. Logistic regression models and categorical data analysis were used to identify associations of patient and tumor characteristics with mutation status. All statistical tests were two-sided.

RESULTS: KRAS (35%) and BRAF (V600E ...


Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper 2015 Harvard Medical School

Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper

Molecular, Cell and Cancer Biology Publications

We have now examined the erythroid phenotype in this zebrafish strain carrying a ZFN genomic knockout of piezo1. Genotyping was performed as previously described. In contrast to the anemic phenotype observed in zebrafish subjected to morpholino knockdown of piezo, the genomic ZFN knockout of piezo1 did not segregate either with anemia in the 3-dpf embryo or with dysmorphic erythrocyte morphology in the adult fish.


Interview With Scott Hamilton Goodnight, Jr., M.D., Scott Hamilton Goodnight, Jr., M.D. (interviewee), Grover C. Bagby, M.D. (interviewer) 2015 Oregon Health & Science University

Interview With Scott Hamilton Goodnight, Jr., M.D., Scott Hamilton Goodnight, Jr., M.D. (Interviewee), Grover C. Bagby, M.D. (Interviewer)

Oral History Collection

In this oral history interview, Scott Goodnight, Jr., M.D., reflects on his life and career in medicine. He begins the interview by discussing his father’s medical school career and practice in downtown Portland and Goodnight’s childhood growing up in Northwest Portland. He goes on to describe his undergraduate and graduate education in medicine at the University of Oregon, meeting his wife Cecelia, and his early involvement in biomedical research. Drafted by the Army, Goodnight also discusses his time spent at the Fitzsimmons General Hospital and General Medicine Clinic as well as the 85th Evacuation Hospital in ...


Off-Target V(D)J Recombination Drives Lymphomagenesis And Is Escalated By Loss Of The Rag2 C Terminus., Martina Mijušković, Yi-Fan Chou, Vered Gigi, Cory R Lindsay, Olga Shestova, Susanna M Lewis, David B Roth 2015 Department of Pathology and Laboratory Medicine, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania; Abramson Family Cancer Research Institute, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania; Department of Genetics and Epidemiology, The Institute of Cancer Research

Off-Target V(D)J Recombination Drives Lymphomagenesis And Is Escalated By Loss Of The Rag2 C Terminus., Martina Mijušković, Yi-Fan Chou, Vered Gigi, Cory R Lindsay, Olga Shestova, Susanna M Lewis, David B Roth

Cardeza Foundation for Hematologic Research

Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification.


Neutrophil Responses To Sterile Implant Materials, Siddharth Jhunjhunwala, Stephanie Aresta-DaSilva, Katherine Tang, David Alvarez, Matthew J. Webber, Benjamin C. Tang, Danya M. Lavin, Omid Veiseh, Joshua C. Doloff, Suman Bose, Arturo Vegas, Minglin Ma, Gaurav Sahay, Alan Chiu, Andrew Bader, Erin Langan, Sean Siebert, Jie Li, Dale L. Greiner, Peter E. Newburger, Ulrich H. von Andrian, Robert Langer, Daniel G. Anderson 2015 Massachusetts Institute of Technology

Neutrophil Responses To Sterile Implant Materials, Siddharth Jhunjhunwala, Stephanie Aresta-Dasilva, Katherine Tang, David Alvarez, Matthew J. Webber, Benjamin C. Tang, Danya M. Lavin, Omid Veiseh, Joshua C. Doloff, Suman Bose, Arturo Vegas, Minglin Ma, Gaurav Sahay, Alan Chiu, Andrew Bader, Erin Langan, Sean Siebert, Jie Li, Dale L. Greiner, Peter E. Newburger, Ulrich H. Von Andrian, Robert Langer, Daniel G. Anderson

Open Access Articles

In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety ...


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