tbuckley/cabot-search huggingface dataset:
The ERBB4/HER4 Intracellular Domain 4ICD Is a BH3-Only Protein Promoting Apoptosis of Breast Cancer Cells
Authors: Anjali Naresh, Weiwen Long, Gregory A. Vidal, William C. Wimley, Luis Marrero, Carolyn I. Sartor, Sian Tovey, Timothy G. Cooke, John M.S. Bartlett, Frank E. Jones
Journal: Cancer Research (2006)

Abstract ERBB4/HER4 (referred to here as ERBB4) is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e., EGFR, ERBB2/HER2/NEU, and ERBB3), which are associated with aggressive forms of human cancers, ERBB4 expression seems to be selectively lost in tumors with aggressive phenotypes. Consistent with this observation, we show that ERBB4 induces apoptosis when reintroduced into breast cancer cell lines or when endogenous ERBB4 is activated by a ligand. We further show that ligand activation and subsequent proteolytic processing of endogenous ERBB4 results in mitochondrial accumulation of the ERBB4 intracellular domain (4ICD) and cytochrome c efflux, the essential and committed step of mitochondrial regulated apoptosis. Our results indicate that 4ICD is functionally similar to BH3-only proteins, proapoptotic members of the BCL-2 family required for initiation of mitochondrial dysfunction through activation of the proapoptotic multi-BH domain proteins BAX/BAK. Similar to other BH3-only proteins, 4ICD cell-killing activity requires an intact BH3 domain and 4ICD interaction with the antiapoptotic protein BCL-2, suppressed 4ICD-induced apoptosis. Unique among BH3-only proteins, however, is the essential requirement of BAK but not BAX to transmit the 4ICD apoptotic signal. Clinically, cytosolic but not membrane ERBB4/4ICD expression in primary human breast tumors was associated with tumor apoptosis, providing a mechanistic explanation for the loss of ERBB4 expression during tumor progression. Thus, we propose that ligand-induced mitochondrial accumulation of 4ICD represents a unique mechanism of action for transmembrane receptors, directly coupling a cell surface signal to the tumor cell mitochondrial apoptotic pathway. (Cancer Res 2006; 66(12): 6412-20)
The Relationship Between Homologous Recombination Repair and the Sensitivity of Human Epidermis to the Size of Daily Doses Over a 5-Week Course of Breast Radiotherapy
Authors: Navita Somaiah, John Yarnold, Frances Daley, Ann Pearson, Lone Gothard, Kai Rothkamm, Thomas Helleday
Journal: Clinical Cancer Research (2012)

Abstract Purpose: A molecular understanding of tissue sensitivity to radiotherapy fraction size is missing. Here, we test the hypothesis that sensitivity to fraction size is influenced by the DNA repair system activated in response to DNA double-strand breaks (DSB). Human epidermis was used as a model in which proliferation and DNA repair were correlated over 5 weeks of radiotherapy. Experimental design: Radiotherapy (25 fractions of 2 Gy) was prescribed to the breast in 30 women with early breast cancer. Breast skin biopsies were collected 2 hours after the 1st and 25th fractions. Samples of contralateral breast skin served as controls. Sections were coimmunostained for Ki67, cyclin A, p21, RAD51, 53BP1, and β1-integrin. Results: After 5 weeks of radiotherapy, the mean basal Ki67 density increased from 5.72 to 15.46 cells per millimeter of basement membrane (P = 0.002), of which the majority were in S/G2 phase, as judged by cyclin A staining (P &amp;lt; 0.0003). The p21 index rose from 2.8% to 87.4% (P &amp;lt; 0.0001) after 25 fractions, indicating cell cycle arrest. By week 5, there was a 4-fold increase (P = 0.0003) in the proportion of Ki67-positive cells showing RAD51 foci, suggesting increasing activation of homologous recombination. Conclusions: Cell cycle arrest in S/G2 phase in the basal epidermis after a 5-week course of radiotherapy is associated with greater use of homologous recombination for repairing DSB. The high fidelity of homologous recombination, which is independent of DNA damage levels, may explain the low-fractionation sensitivity of tissues with high-proliferative indices, including self-renewing normal tissues and many cancers. Clin Cancer Res; 18(19); 5479–88. ©2012 AACR.
Transfection of the Primate Malaria Parasite <i>Plasmodium knowlesi</i> Using Entirely Heterologous Constructs
Authors: Anna M. van der Wel, Ana M. Tomás, Clemens H.M. Kocken, Pawan Malhotra, Chris J. Janse, Andrew P. Waters, Alan W. Thomas
Journal: The Journal of Experimental Medicine (1997)

The recently developed transfection systems for Plasmodium berghei and Plasmodium falciparum offer important new tools enabling further insight into the biology of malaria parasites. These systems rely upon artificial parasite–host combinations which do not allow investigation into the complex interactions between parasites and their natural hosts. Here we report on stable transfection of Plasmodium knowlesi (a primate malaria parasite that clusters phylogenetically with P. vivax) for which both natural and artificial experimental hosts are available. Transfection of this parasite offers the opportunity to further analyze the biology of antigens not only in a natural host but also in hosts that are closely related to humans. To facilitate future development of integration-dependent transfection in P. knowlesi, completely heterologous plasmids that would reduce homologous recombination at unwanted sites in the genome were constructed. These plasmids contained the pyrimethamine-resistant form of dihydrofolate reductase-thymidylate synthase (dhfr-ts) from Toxoplasma gondii or P. berghei, under control of either (a) P. berghei or (b) P. falciparum promoters. Plasmids were electroporated into mature P. knowlesi schizonts and these cells were injected into rhesus monkeys (Macaca mulatta). After pyrimethamine treatment of these monkeys, resistant parasites were obtained that contained the plasmids. Promoter regions of both P. berghei and P. falciparum controlling dhfr-ts expression were effective in conferring pyrimethamine resistance in P. knowlesi, indicating that common signals control gene expression in phylogenetically distant Plasmodium species.
Src Stimulates Fibroblast Growth Factor Receptor-2 Shedding by an ADAM15 Splice Variant Linked to Breast Cancer
Authors: Thorsten Maretzky, Sylvain M. Le Gall, Susanne Worpenberg-Pietruk, Jörg Eder, Christopher M. Overall, Xin-Yun Huang, Zaruhi Poghosyan, Dylan R. Edwards, Carl P. Blobel
Journal: Cancer Research (2009)

Abstract ADAMs (a disintegrin and metalloproteinase) have important roles in development and diseases such as cancer. Previously, an ADAM15 splice variant (ADAM15B), which contains an inserted cytoplasmic Src-binding site, was linked to clinical aggressiveness in breast cancer, yet little was known about how this splice variant affects the function of ADAM15. Here, we show that ADAM15B has enhanced catalytic activity in cell-based assays compared with ADAM15A, which lacks a Src-binding site, using shedding of fibroblast growth factor receptor 2iiib variant as an assay for catalytic activity. Moreover, the enhanced activity of ADAM15B compared with ADAM15A depends on Src because it is abolished by Src-kinase inhibitors and in Src−/− cells, but not in Src−/− cells rescued with Src. These findings provide insights into the mechanism of how a splice variant linked to clinical agressiveness in breast cancer causes increased activity of ADAM15B, and suggest that inhibitors of the ADAM15 protease activity or of the interaction of ADAM15B with Src could be useful to treat breast cancer in patients with dysregulated ADAM15B. [Cancer Res 2009;69(11):4573–6]
Referral, Receipt, and Completion of Chemotherapy in Patients With Early-Stage Breast Cancer Older Than 65 Years and at High Risk of Breast Cancer Recurrence
Authors: Diana S.M. Buist, Jessica Chubak, Marianne Prout, Marianne Ulcickas Yood, Jaclyn L.F. Bosco, Soe Soe Thwin, Heather Taffet Gold, Cynthia Owusu, Terry S. Field, Virginia P. Quinn, Feifei Wei, Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2009)

Purpose Some women with early-stage breast cancer are at higher risk of recurrence and can benefit from chemotherapy. We describe patterns of referral, receipt, and completion of chemotherapy among older women at high risk of recurrence. Patients and Methods A total of 2,124 women age 65 years or older who were diagnosed with early-stage breast cancer between 1990 and 1994 and 1996 to 1999 were included; 1,090 of these were at high risk of recurrence. We reviewed medical records to categorize chemotherapy outcomes as follows: did not discuss or were not referred to a medical oncologist (n = 133); discussed and/or referred to a medical oncologist but received no chemotherapy (n = 742); received an incomplete chemotherapy course (n = 29), or received a completed chemotherapy course (n = 186). Results Overall, 19.7% of high-risk women received any chemotherapy, and 86.5% of these women completed their chemotherapy courses. Just greater than 10% of high-risk women did not have a discussion about chemotherapy as part of breast cancer treatment documented in the medical record; these women also received fewer diagnostic assessments of their initial tumors. Conclusion Individuals who receive chemotherapy for early-stage breast cancer are a select subgroup of patients at high risk of recurrence. This study identifies characteristics of women who were referred for and who received chemotherapy, and this study plays an important role in understanding generalizability of studies that examine chemotherapy treatment effectiveness. Outcomes after breast cancer could continue to be improved with increased receipt of chemotherapy among older women at high risk of breast cancer recurrence.
Retinoic Acid and VEGF Delay Smooth Muscle Relative to Endothelial Differentiation to Coordinate Inner and Outer Coronary Vessel Wall Morphogenesis
Authors: Ana P. Azambuja, Victor Portillo-Sánchez, Mariliza V. Rodrigues, Samantha V. Omae, Deborah Schechtman, Bryan E. Strauss, Eugenia Costanzi-Strauss, José E. Krieger, José M. Perez-Pomares, José Xavier-Neto
Journal: Circulation Research (2010)

Major coronary vessels derive from the proepicardium, the cellular progenitor of the epicardium, coronary endothelium, and coronary smooth muscle cells (CoSMCs). CoSMCs are delayed in their differentiation relative to coronary endothelial cells (CoEs), such that CoSMCs mature only after CoEs have assembled into tubes. The mechanisms underlying this sequential CoE/CoSMC differentiation are unknown. Retinoic acid (RA) is crucial for vascular development and the main RA-synthesizing enzyme is progressively lost from epicardially derived cells as they differentiate into blood vessel types. In parallel, myocardial vascular endothelial growth factor (VEGF) expression also decreases along coronary vessel muscularization.We hypothesized that RA and VEGF act coordinately as physiological brakes to CoSMC differentiation.In vitro assays (proepicardial cultures, cocultures, and RALDH2 [retinaldehyde dehydrogenase-2]/VEGF adenoviral overexpression) and in vivo inhibition of RA synthesis show that RA and VEGF act as repressors of CoSMC differentiation, whereas VEGF biases epicardially derived cell differentiation toward the endothelial phenotype.Experiments support a model in which early high levels of RA and VEGF prevent CoSMC differentiation from epicardially derived cells before RA and VEGF levels decline as an extensive endothelial network is established. We suggest this physiological delay guarantees the formation of a complex, hierarchical, tree of coronary vessels.
The endogenous inhibitor of Akt, CTMP, is critical to ischemia-induced neuronal death
Authors: Takahiro Miyawaki, Dimitry Ofengeim, Kyung-Min Noh, Adrianna Latuszek-Barrantes, Brian A Hemmings, Antonia Follenzi, R Suzanne Zukin
Journal: Nature Neuroscience (2009)
Combination of International Scoring System 3, High Lactate Dehydrogenase, and t(4;14) and/or del(17p) Identifies Patients With Multiple Myeloma (MM) Treated With Front-Line Autologous Stem-Cell Transplantation at High Risk of Early MM Progression–Related Death
Authors: Philippe Moreau, Michele Cavo, Pieter Sonneveld, Laura Rosinol, Michel Attal, Annalisa Pezzi, Hartmut Goldschmidt, Juan Jose Lahuerta, Gerald Marit, Antonio Palumbo, Bronno van der Holt, Joan Bladé, Maria Teresa Petrucci, Kai Neben, Jesus san Miguel, Francesca Patriarca, Henk Lokhorst, Elena Zamagni, Cyrille Hulin, Norma Gutierrez, Thierry Facon, Denis Caillot, Lotfi Benboubker, Jean-Luc Harousseau, Xavier Leleu, Hervé Avet-Loiseau, Jean-Yves Mary
Journal: Journal of Clinical Oncology (2014)

Purpose To construct and validate among patients with multiple myeloma (MM) who were treated with intensive therapy a prognostic index of early MM progression–related death. Patients and Methods Patient-level data from the Intergroupe Francophone du Myélome (IFM) 2005-01 trial (N = 482) were used to construct the prognostic index. The event was MM progression–related death within 2 years from treatment initiation. The index was validated using data from three other trials: the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) 26866138-MMY-3006 trial (N = 480), the Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA)–GEMMENOS65 trial (N = 390), and the Hemato-Oncologie voor Volwassenen Nederland (HOVON) –65/German-Speaking Myeloma Multicenter Group (GMMG) –HD4 trial (N = 827). Results The risk of early MM progression–related death was related to three independent prognostic variables: lactate dehydrogenase (LDH) higher than than normal, International Staging System 3 (ISS3), and adverse cytogenetics [t(4;14) and/or del(17p)]. These three variables enabled the definition of an ordinal prognostic classification composed of four scores (0 to 3). Patients with a score of 3, defined by the presence of t(4;14) and/or del(17p) in addition to ISS3 and/or high LDH, comprised 5% (20 of 387 patients) to 8% (94 of 1,139 patients) of the patients in the learning and validation samples, respectively, and they had a very poor prognosis. When applied to the population of 855 patients who had received bortezomib-based induction therapy in the four trials, the prognostic classification was also able to segregate patients into four categories, with a very poor prognosis attributed to patients with a score of 3. Conclusion Our model allows the simple definition of a subgroup of MM patients at high risk of early MM progression–related death despite the use of the most modern and effective strategies.
Incidence of Type 1 Diabetes in Mexico: Data From an Institutional Register 2000–2010
Authors: Rita A. Gómez-Díaz, Gabriela Pérez-Pérez, Irina Tatiana Hernández-Cuesta, Julia del Carmen Rodríguez-García, Raúl Guerrero-López, Carlos A. Aguilar-Salinas, Niels H. Wacher
Journal: Diabetes Care (2012)

The incidence of type 1 diabetes is increasing worldwide. However, scant data exist about the prevalence or the incidence of type 1 diabetes in children (1,2). The aim of this study was to describe the number of new cases with type 1 diabetes reported in a pediatric population covered by the Instituto Mexicano del Seguro Social during a 10-year period (2000–2010).

Data registered by the Direccion de Prestaciones Medicas of the Instituto Mexicano del Seguro Social collected during 2000–2010 were the source of information. Children with incident type 1 diabetes were identified using ICD-10-CM diagnostic codes. The Instituto Mexicano del Seguro Social provides health care to workers nationwide.

During the study years, the number of new cases with type 1 …
Comprehensive cytogenetic and molecular genetic characterization of the TI-1 acute myeloid leukemia cell line reveals cross-contamination with K-562 cell line
Authors: Laura J. Rush, Kristiina Heinonen, Krzysztof Mrózek, Bryan J. Wolf, Mohamed Abdel-Rahman, Jadwiga Szymanska, Paivi Peltomäki, Fehmida Kapadia, Clara D. Bloomfield, Michael A. Caligiuri, Christoph Plass
Journal: Blood (2002)
Survey of artificial tear and saliva usage among patients with Sjogren's syndrome
Authors: D MULHERIN
Journal: Annals of the Rheumatic Diseases (2001)

Sjogren's syndrome (SS), a chronic immune mediated disease associated with xerostomia and keratoconjunctivitis sicca, may occur alone (primary SS) or with other autoimmune diseases (secondary SS).1 The benefits of substitution treatment for dry eyes and mouth seem very variable. This survey assessed patients' experience of the wide variety of tear and saliva substitutes available.

Patients with SS, from Cannock Chase Hospital, University Hospital Birmingham, City Hospital Birmingham, or Birmingham Heartlands and Solihull Hospitals, completed a questionnaire, returned at their clinic visit or by prepaid post. SS was defined by the presence of four from six EC diagnostic criteria, with the modification that patients with primary SS must have anti-Ro antibodies (by enzyme linked immunosorbent assay (ELISA) or countercurrent immunoelectrophoresis) and/or have had a lip biopsy demonstrating features typical of SS.2 The questionnaire asked patients to identify, from a comprehensive list, all tear and saliva substitutes that they had ever heard of, had ever used, or were currently using, to identify useful source(s) of information about substitute treatment, and to rate the effectiveness of any treatments they had ever …
Evidence for human T cell lymphoma-leukemia virus infection of family members of human T cell lymphoma-leukemia virus positive T cell leukemia-lymphoma patients.
Authors: M Robert-Guroff, V S Kalyanaraman, W A Blattner, M Popovic, M G Sarngadharan, M Maeda, D Blayney, D Catovsky, P A Bunn, A Shibata, Y Nakao, Y Ito, T Aoki, R C Gallo
Journal: The Journal of Experimental Medicine (1983)

Sera of family members of patients from the United States, the Caribbean, and Japan, with human T cell lymphoma-leukemia virus (HTLV) associated T cell malignancies, possess HTLV-specific antibodies directed against internal structural components of HTLV, p24 and p19. The prevalence of antibodies to HTLV is greater in family members than in random healthy donors, which supports the infectious nature of HTLV and its association with particular aggressive T cell malignancies. Expression of HTLV p24 and p19 has also been observed in cultured T cells of some healthy relatives, and intact virus particles have been released from cells of one possibly pre-leukemic family member.
Role of nitric oxide in gastric motor and sensory functions in healthy subjects
Authors: S D Kuiken, M Vergeer, S H Heisterkamp, G N J Tytgat, G E E Boeckxstaens
Journal: Gut (2002)

Impaired accommodation and hypersensitivity to distension of the proximal stomach are considered to be important factors in the pathogenesis of dyspeptic complaints. As fundus relaxing agents may be effective in the treatment of these symptoms, insight into the mediators involved in fundic accommodation and associated perceptual responses is important. Therefore, we studied the effect of nitric oxide (NO) synthase inhibition by N(G)-monomethyl-L-arginine (L-NMMA) on fundic tone, postprandial sensations, and gastric perception in healthy volunteers.Eighteen healthy volunteers participated in a double blind, placebo controlled, randomised study. They underwent a gastric barostat study to evaluate the effect of L-NMMA on meal and distension induced sensations and on fundic relaxation in response to oral meal intake, intraduodenal lipid, and glucagon administration.Compared with placebo, L-NMMA decreased fundic volume after oral meal intake (438 (55) v 304 (67) ml; n=8; p<0.05) and during intraduodenal lipid infusion (384 (37) v 257 (43) ml; n=10; p<0.05) but not after glucagon injection (570 (62) v 540 (52) ml; n=4; p=0.4). In addition, basal fundic volume was significantly reduced by L-NMMA. Scores for nausea and satiation were decreased by L-NMMA after oral meal intake but not during intraduodenal lipid infusion. Perception scores to gastric distension were not altered by L-NMMA.NO is involved in maintaining basal fundic tone and in meal induced fundic relaxation in humans, but not in visceral perception.
Sinus Microbiome Diversity Depletion and <i>Corynebacterium tuberculostearicum</i> Enrichment Mediates Rhinosinusitis
Authors: Nicole A. Abreu, Nabeetha A. Nagalingam, Yuanlin Song, Frederick C. Roediger, Steven D. Pletcher, Andrew N. Goldberg, Susan V. Lynch
Journal: Science Translational Medicine (2012)

Enrichment of Corynebacterium tuberculostearicum caused by depletion of the sinus microbiome contributes to chronic rhinosinusitis.
Lead Poisoning From Restoration of Old Homes
Authors: Muriel D. Wolf
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Within the past two years, lead poisoning has been diagnosed in the children of two families involved in the restoration of their homes in the Capitol Hill section of Washington, DC. Both parents in one family were also found to have lead poisoning. The majority of Capitol Hill houses were built in the Victorian era, but vary from the Federal period to the 1920s, with much private renovation and restoration of these homes in the past ten years. <h3>Report of Cases.—Case 1.—</h3> This family bought and moved into a Victorian house on Capitol Hill in 1969. They began extensive restoration, while living in it; this work included burning and scraping of old paint. Aware of the risk of lead poisoning, the mother had the children's blood levels checked on several occasions during the remodeling. At first low, the lead concentrations increased (Table 1). There was
Effect of daily versus intermittent sunscreen application on solar simulated UV radiation?induced skin response in humans
Authors: Tania J. Phillips, Jag Bhawan, Mina Yaar, Ysabel Bello, Danielle LoPiccolo, J.Frank Nash
Journal: Journal of the American Academy of Dermatology (2000)

<h2>Abstract</h2> <b>Background:</b> Acute and chronic skin damage occurs as a consequence of solar UV radiation exposure. To diminish such skin damage, the dermatologic community advocates the daily use of sunscreens as part of a sun avoidance strategy. <b>Objective:</b> We determined the effectiveness of a sunscreen product with a sunscreen protection factor (SPF) of 15 applied daily in preventing UV-induced histologic damage in human skin compared with the protection afforded by sunscreens with equal or higher SPF applied intermittently. <b>Methods:</b> Twenty-four subjects were exposed to 2 minimal erythema doses of solar-simulated UV on 4 consecutive days. Three sunscreen products were applied to the buttock of each subject. One SPF 15 product was applied daily before exposure to UV and, to simulate intermittent product use, an SPF 15 or SPF 29 product was applied on 3 of 4 days, with one missed application on days 2, 3, or 4. Skin biopsy specimens were taken and processed for routine and immunohistochemical staining. Changes in number of sunburn cells and Langerhans cells as well as degree of inflammatory infiltrate and lysozyme immunostaining were determined. <b>Results:</b> There was a statistically significant increase in the number of sunburn cells, degree of inflammation, and intensity of lysozyme staining, and there was a decrease in the number of Langerhans cells at sites where sunscreen application was missed as compared with unirradiated control and daily SPF 15 sunscreen-treated sites. <b>Conclusion:</b> Our data suggest that daily use of a sunscreen reduces the skin damage produced by UV exposure compared with intermittent use of equal or higher SPF products. The daily application of sunscreens in appropriate quantities reduces the harmful effects of solar UV radiation on skin. Compliance is essential for maximal benefit of sunscreens. (J Am Acad Dermatol 2000;43:610-8.).