tbuckley/cabot-search huggingface dataset:
Spotlight on measles 2010: Preliminary report of an ongoing measles outbreak in a subpopulation with low vaccination coverage in Berlin, Germany, January-March 2010
Authors: J Bätzing-Feigenbaum, U Pruckner, A Beyer, G Sinn, A Dinter, A Mankertz, A Siedler, A Schubert, M Suckau
Journal: Eurosurveillance (2010)

Since early January 2010, Berlin has been experiencing a measles outbreak with 62 cases as of 31 March. The index case acquired the infection in India. In recent years, measles incidence in Berlin has been lower than the German average and vaccination coverage in school children has increased since 2001. However, this outbreak involves schools and kindergartens with low vaccination coverage and parents with critical attitudes towards vaccination, which makes the implementation of public health interventions challenging.
Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi‐center study of iron overload
Authors: Ellen B. Fung, Paul Harmatz, Meredith Milet, Samir K. Ballas, Laura De Castro, Ward Hagar, William Owen, Nancy Olivieri, Kim Smith‐Whitley, Deepika Darbari, Winfred Wang, Elliott Vichinsky
Journal: American Journal of Hematology (2006)

A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n = 199), and 64 non-Tx-SCD subjects to describe the frequency of iron-related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 +/- 11 years, mean +/- SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thal or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0-2.5) or non-Tx-SCD (RR = 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r= 0.20; P = 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 +/- 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality.
Third-World Interloper
Authors: Don Riesenberg
Journal: JAMA (1987)

I awake to the stifling heat of the Artibonite Valley. It is a place where the wind rarely stirs and where, in Haiti's summer of 1983, rain will not fall. A sense of purpose propels me along the dirt path from my concrete-block house. I am armed, as it were, with a decade of learning, teaching, and practicing internal medicine: a decade of intravascular catheters, enzyme inhibitors, and insulin pumps. It is my first day on call at Hopital Albert Schweitzer.  I enter the outpatient clinic through the rear entrance, past the hospital kitchen, where the first of the day's two meals is being prepared. We have very many today, Doctor, the Haitian medical assistant announces as we pass between the rows of wooden benches on which sit or lie today's patients. They have come on foot or by donkey, an overnight journey for many, to see the American doctor.
Human embryonic stem cells differentiate into functional renal proximal tubular–like cells
Authors: Karthikeyan Narayanan, Karl M. Schumacher, Farah Tasnim, Karthikeyan Kandasamy, Annegret Schumacher, Ming Ni, Shujun Gao, Began Gopalan, Daniele Zink, Jackie Y. Ying
Journal: Kidney International (2013)
AIDS and declining support for dependent elderly people in Africa: retrospective analysis using demographic and health surveys
Authors: T. Kautz, E. Bendavid, J. Bhattacharya, G. Miller
Journal: BMJ (2010)

<b>Objectives</b> To determine the relation between the HIV/AIDS epidemic and support for dependent elderly people in Africa. <b>Design </b>Retrospective analysis using data from Demographic and Health Surveys. <b>Setting </b>22 African countries between 1991 and 2006. <b>Participants</b> 123 176 individuals over the age of 60. <b>Main outcome measures</b> We investigated how three measures of the living arrangements of older people have been affected by the HIV/AIDS epidemic: the number of older individuals living alone (that is, the number of unattended elderly people); the number of older individuals living with only dependent children under the age of 10 (that is, in missing generation households); and the number of adults age 18-59 (that is, prime age adults) per household where an older person lives. <b>Results</b> An increase in annual AIDS mortality of one death per 1000 people was associated with a 1.5% increase in the proportion of older individuals living alone (95% CI 1.2% to 1.9%) and a 0.4% increase in the number of older individuals living in missing generation households (95% CI 0.3% to 0.6%). Increases in AIDS mortality were also associated with fewer prime age adults in households with at least one older person and at least one prime age adult (P&lt;0.001). These findings suggest that in our study countries, which encompass 70% of the sub-Saharan population, the HIV/AIDS epidemic could be responsible for 582 200-917 000 older individuals living alone without prime age adults and 141 000-323 100 older individuals being the sole caregivers for young children. <b>Conclusions</b> Africa’s HIV/AIDS epidemic might be responsible for a large number of older people losing their support and having to care for young children. This population has previously been under-recognised. Efforts to reduce HIV/AIDS deaths could have large “spillover” benefits for elderly people in Africa.
Certification assays for HIV-1-based vectors: frequent passage of gag sequences without evidence of replication-competent viruses
Authors: Lakshmi Sastry, Yi Xu, Terry Johnson, Kunal Desai, David Rissing, Jonathan Marsh, Kenneth Cornetta
Journal: Molecular Therapy (2003)

A principal concern regarding the safety of HIV-1-based vectors is replication-competent lentivirus (RCL). We have developed two PCR assays for detecting RCL; the first detects recombination between gag regions in the transfer vector and the packaging construct (sensitivity of detection approximately 10-100 copies of target sequence). The second assay uses real-time PCR to detect vesicular stomatitis virus glycoprotein (VSVG) envelope DNA (sensitivity approximately 5-50 VSVG sequences). In an attempt to amplify any RCL, test vectors were used to transduce C8166 and 293 cells, which were then screened weekly for 3 weeks. Psi-gag recombinants were routinely detected (20 of 21 analyses) in four transductions using the RRL-CMV-GFP vector. In contrast, VSVG sequences were detected only once in 21 analyses. Interestingly, p24 levels (as measured by ELISA) were occasionally detectable after 3 weeks of culture. To determine if a true RCL was present, 21-day cell-free medium was used to transduce naïve cells. No evidence of psi-gag or VSVG transfer was detected, indicating that the recombination events were insufficient to reconstitute a true RCL. These findings have important implications for the design and safety of HIV-1-based vectors intended for clinical applications.
Incidence of Type 1 Diabetes Has Doubled in Rome and the Lazio Region in the 0- to 14-Year Age-Group: A 6-Year Prospective Study (2004–2009)
Authors: Carla Bizzarri, Patrizia Ippolita Patera, Claudia Arnaldi, Stefano Petrucci, Maria Luisa Manca Bitti, Raffaella Scrocca, Silvia Manfrini, Rosalba Portuesi, Raffaella Buzzetti, Marco Cappa, Paolo Pozzilli
Journal: Diabetes Care (2010)

Incidence of type 1 diabetes is rising, especially among younger children (1,2). We evaluated type 1 diabetes incidence in the years 2004–2009 among subjects <15 years of age residing in Rome and in its region (Lazio). Primary ascertainment was based in diabetes clinics and specialized hospitals, whereas secondary independent ascertainment was from the archives where all patients register to receive free medications within the National Health System.

We identified 666 subjects (369 males and 297 females) with type 1 diabetes (American Diabetes Association criteria diagnosed by a pediatrician/diabetologist). All but 10 patients (1.5%) were Caucasians; 95% of patients tested positive for at least one autoantibody (insulin autoantibody, GAD antibody, or insulinoma-associated protein 2 [IA2]), 175 children …
Aberrant Expression of Cortactin in Head and Neck Squamous Cell Carcinoma Cells Is Associated with Enhanced Cell Proliferation and Resistance to the Epidermal Growth Factor Receptor Inhibitor Gefitinib
Authors: Paul Timpson, Ashleigh S. Wilson, Gillian M. Lehrbach, Robert L. Sutherland, Elizabeth A. Musgrove, Roger J. Daly
Journal: Cancer Research (2007)

Abstract The CTTN gene (formerly designated EMS1), encodes cortactin, a key regulator of dynamic actin networks. Both CTTN and CCND1, the latter encoding the cell cycle regulator cyclin D1, reside at chromosomal locus 11q13, a region commonly amplified in breast cancers and head and neck squamous cell carcinoma (HNSCC). Previously, we identified a novel role for cortactin in cancer cells, whereby cortactin overexpression attenuated ligand-induced down-regulation of the epidermal growth factor (EGF) receptor (EGFR), leading to sustained signaling. However, how this affected growth factor–induced cellular responses was unclear. Here, by modulation of cortactin expression in a panel of HNSCC cell lines, we show that cortactin overexpression enhances serum- and EGF-stimulated proliferation under both anchorage-dependent and anchorage-independent conditions and also increases resistance to anoikis (detachment-induced apoptosis). These effects are associated with increased activation of extracellular signal-regulated kinase and/or AKT. Furthermore, we report that cortactin stabilizes the c-MET receptor tyrosine kinase and enhances hepatocyte growth factor–induced mitogenesis and cell scattering. Therefore, cortactin may modulate signaling by a broader range of receptors than originally proposed and thereby affect a variety of responses. Finally, we have determined that cortactin overexpression, either alone or in combination with cyclin D1 up-regulation, promotes resistance to the EGFR kinase inhibitor gefitinib. These findings indicate that cortactin may play multiple roles in progression of HNSCC and should be evaluated as a marker of prognosis, disease progression, and therapeutic responsiveness, particularly to EGFR-directed agents. [Cancer Res 2007;67(19):9304–14]
Response to Open Peer Commentaries on “Stem Cell Tourism and the Power of Hope”
Authors: Charles E. Murdoch, Christopher Thomas Scott
Journal: The American Journal of Bioethics (2010)

We wish to thank all OPC contributors for their thoughtful comments, suggestions and criticisms. Regenberg (2010)—We believe that the promotion of open discourse through use of social media as suggested by Regenberg is a valuable suggestion if carefully qualified. Most critically: the academic and medical community’s engagement with these technologies must be ethical, efficient, and thoughtful; and indeed, the OPC seems well aware of this requirement. With proper training to avoid that platform’s well-documented and undeniable pitfalls (particularly those specific to scientists and clinicians), funding to make it a viable part of their work, and proper institutional infrastructure, social media can be harnessed as a valuable tool enabling direct communication with that small subset of individuals who are seriously contemplating stem cell tourism. Sipp (2010)—Sipp identifies the “harmless placebo” argument we raise as a critical issue to be wrestled with. We agree, and indeed, this issue proved to be a matter of considerable uncertainty and turmoil for us as we wrote the target article. However, we note that the question we ultimately chose to articulate is very narrowly circumscribed, to the point where it verges on a thought experiment: namely, “If a treatment is generally safe, uncostly relative to the subset of patients’ means, patients are fully apprised of the uncertainties and realistic possible outcomes, and a net benefit arises, does harm result?” We agree that many patients cannot afford their procedures, and that there may be increased publicity of inefficacious treatments. However, the former is explicitly excluded from consideration by our question’s wording, and we would argue that the latter may be as well, if no net public health benefit arises from any new publicity. When its narrow circumscription is pursued to its extreme, our question becomes a philosophical reflection on why we are opposed to certain kinds of procedures in the absence of concrete harms. Whether or not a real-life exam-
Abstract 4717: Final results from the Phase I study of MetMAb, a monovalent antagonist antibody to the receptor Met, dosed as single agent and in combination with bevacizumab in patients with advanced solid malignancies
Authors: Rebecca A. Moss, John G. Bothos, Premal H. Patel, Amy C. Peterson, Steve Eppler, Shuang Bai, Ihsan Nijem, Luc Desnoyers, Surinder Kaur, Jiping Zha, Wei Yu, Joe Simpson, Mark J. Ratain, Antoinette R. Tan, Mark N. Stein, Janice M. Mehnert, Ravi Salgia
Journal: Cancer Research (2011)

Abstract Background: The receptor tyrosine kinase Met and/or its ligand, hepatocyte growth factor (HGF), are frequently over-expressed in cancers. Aberrant Met activation can enhance invasion, proliferation, and survival and may promote angiogenesis. MetMAb was uniquely engineered as a recombinant, humanized, monovalent monoclonal antibody to act as an antagonist of HGF-induced Met signaling. Materials and Methods: This 3+3 dose-escalation study consisted of three phases: 1) dose-escalation evaluating 1, 4, 10, 15, 20 and 30 mg/kg IV Q3W; 2) expansion at 15mg/kg IV Q3W; and 3) combination testing MetMAb, at 10 and 15mg/kg IV Q3W, plus bevacizumab (15mg/kg Q3W). Pre- and post- dose serum was collected for evaluation of pharmacodynamic biomarkers that could be affected by inhibition of Met and/or VEGF signaling. Results: 43 patients were treated in this study (21 in escalation, 13 in expansion, and 9 in combination). MetMAb has a half-life of approximately 11 days, and there were no apparent PK interactions with bevacizumab. MetMAb was generally well tolerated, both alone and in combination. The most frequent treatment-related adverse events included: fatigue, peripheral edema and hypoalbuminemia. In patients treated with the combination, no Grade 3-5 treatment-related adverse events were reported; a Grade 1, and dose-limiting adverse event of hemoptysis was reported in a patient who had central-necrosis of pulmonary metastases. A patient with gastric carcinoma achieved a complete response after 4 cycles of single-agent MetMAb; this patient came off study after 10 cycles with a sustained complete response. Conclusions: MetMAb, when administered as a single-agent, or in combination with bevacizumab was generally safe and well tolerated. A Phase II trial testing MetMAb in combination with bevacizumab and paclitaxel in patients with triple negative breast cancer is currently ongoing, while a Phase III trial testing MetMAb in combination with erlotinib in advanced NSCLC patients is planned. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4717. doi:10.1158/1538-7445.AM2011-4717
Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation
Authors: Volker Rudolph, René P Andrié, Tanja K Rudolph, Kai Friedrichs, Anna Klinke, Birgit Hirsch-Hoffmann, Alexander P Schwoerer, Denise Lau, XiaoMing Fu, Karin Klingel, Karsten Sydow, Michael Didié, Anika Seniuk, Eike-Christin von Leitner, Katalin Szoecs, Jan W Schrickel, Hendrik Treede, Ulrich Wenzel, Thorsten Lewalter, Georg Nickenig, Wolfram-Hubertus Zimmermann, Thomas Meinertz, Rainer H Böger, Hermann Reichenspurner, Bruce A Freeman, Thomas Eschenhagen, Heimo Ehmke, Stanley L Hazen, Stephan Willems, Stephan Baldus
Journal: Nature Medicine (2010)
Hypertension Crisis
Authors: Thomas A. Keith
Journal: JAMA (1977)

Situations requiring immediate lowering of systemic blood pressure are infrequent. Certain clinical syndromes resulting from or complicated by severe hypertension demand vigorous, usually parenteral, antihypertensive therapy. Such syndromes include (1) diastolic hypertension accompanied by sudden disruption of cerebral function, (2) dissecting or leaking aortic aneurysm; (3) accelerated or malignant hypertension, (4) toxemia of pregnancy when either the fetus' or the mother's life is immediately threatened, (5) some instances of diastolic hypertension and acute left ventricular failure, (6) uncontrolled hypertension in the patient who requires emergency surgery, (7) refractory elevation of the diastolic pressure in the kidney transplant patient, and (8) refractory hypertension complicating myocardial infarction or angina. Drugs useful in acutely lowering blood pressure include diazoxide, sodium nitroprusside, methyldopa intravenously, reserpine intramuscularly, and trimethaphan camsylate intravenously. Use of furosemide reinforces the hypotensive effect of these agents. Theoretical advantages and disadvantages of these agents are not always encountered in clinical use.
Delivery of AAV-IGF-1 to the CNS Extends Survival in ALS Mice Through Modification of Aberrant Glial Cell Activity
Authors: James C Dodge, Amanda M Haidet, Wendy Yang, Marco A Passini, Mark Hester, Jennifer Clarke, Eric M Roskelley, Christopher M Treleaven, Liza Rizo, Heather Martin, Soo H Kim, Rita Kaspar, Tatyana V Taksir, Denise A Griffiths, Seng H Cheng, Lamya S Shihabuddin, Brian K Kaspar
Journal: Molecular Therapy (2008)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. Recent work in rodent models of ALS has shown that insulin-like growth factor-1 (IGF-1) slows disease progression when delivered at disease onset. However, IGF-1's mechanism of action along the neuromuscular axis remains unclear. In this study, symptomatic ALS mice received IGF-1 through stereotaxic injection of an IGF-1-expressing viral vector to the deep cerebellar nuclei (DCN), a region of the cerebellum with extensive brain stem and spinal cord connections. We found that delivery of IGF-1 to the central nervous system (CNS) reduced ALS neuropathology, improved muscle strength, and significantly extended life span in ALS mice. To explore the mechanism of action of IGF-1, we used a newly developed in vitro model of ALS. We demonstrate that IGF-1 is potently neuroprotective and attenuates glial cell–mediated release of tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Our results show that delivering IGF-1 to the CNS is sufficient to delay disease progression in a mouse model of familial ALS and demonstrate for the first time that IGF-1 attenuates the pathological activity of non-neuronal cells that contribute to disease progression. Our findings highlight an innovative approach for delivering IGF-1 to the CNS. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. Recent work in rodent models of ALS has shown that insulin-like growth factor-1 (IGF-1) slows disease progression when delivered at disease onset. However, IGF-1's mechanism of action along the neuromuscular axis remains unclear. In this study, symptomatic ALS mice received IGF-1 through stereotaxic injection of an IGF-1-expressing viral vector to the deep cerebellar nuclei (DCN), a region of the cerebellum with extensive brain stem and spinal cord connections. We found that delivery of IGF-1 to the central nervous system (CNS) reduced ALS neuropathology, improved muscle strength, and significantly extended life span in ALS mice. To explore the mechanism of action of IGF-1, we used a newly developed in vitro model of ALS. We demonstrate that IGF-1 is potently neuroprotective and attenuates glial cell–mediated release of tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Our results show that delivering IGF-1 to the CNS is sufficient to delay disease progression in a mouse model of familial ALS and demonstrate for the first time that IGF-1 attenuates the pathological activity of non-neuronal cells that contribute to disease progression. Our findings highlight an innovative approach for delivering IGF-1 to the CNS.
The effect of molecules in mother-of-pearl on the decrease in bone resorption through the inhibition of osteoclast cathepsin K
Authors: Denis Duplat, Marlène Gallet, Sophie Berland, Arul Marie, Lionel Dubost, Marthe Rousseau, Saïd Kamel, Christian Milet, Michel Brazier, Evelyne Lopez
Journal: Biomaterials (2007)
Abstract 1906: Mechanisms of resistance to EGFR tyrosine kinase inhibitors involving HER-family ligands and receptors
Authors: Kentaro Iwanaga, Naoko Sueoka-Aragane, Akemi Sato, Tomomi Nakamura, Naomi Kobayashi, Eisaburo Sueoka, Shinya Kimura
Journal: Cancer Research (2012)

Abstract Known mechanisms of acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI), including the second mutation of EGFR, T790M, MET amplification, and HGF overexpression, explain approximately 60% of cases, but the remaining mechanisms have not been clarified. To investigate novel mechanisms of acquired resistance to EGFR-TKI, we examined HER-family ligands and HER-family receptor status in non-small cell lung carcinoma (NSCLC) cell lines (n=13). Cell lines were divided into two groups with respect to EGFR-TKI sensitivity: highly sensitive (HCC827, PC-9, HCC2935, and HCC4006) and resistant (H1395, H1666, H596, H1437, A549, H226B, H1299, H460, H1792). We examined expression levels of eleven HER-family ligands_EGF, TGFβ, amphiregulin (AREG), betacellulin (BTC), HB-EGF, epigen (EPGN), epiregulin (EREG), and neuregulin (NRG) 1, NRG2, NRG3, and NRG4_in these cell lines. NRG2, NRG4, and EPGN were expressed at 39.5-, 31.4-, and 6.5-fold higher levels, respectively, in EGFR-TKI primary resistant NSCLC cell lines than in highly sensitive cell lines, whereas TGFA, EGF, and AREG were expressed at 0.22-, 0.3-, and 0.34-fold lower levels. Phosphorylation of EGFR was elevated in sensitive cell lines compared to resistant cell lines, but HER2-4 receptors did not evidence a difference in phsophorylation. These results suggest that the EGFR pathway is activated in sensitive cell lines, and HER2-4, which binds to EPGN, EREG, NRG2, and NRG4, might be activated in resistant cell lines. We prepared cell lines HCC827GR and HCC827ER, derived from HCC827, which acquired resistance to gefitinib or erlotinib, respectively. We analyzed HER-family ligands and receptors using these cell lines. Compared to parent cells, EPGN, EREG, HB-EGF, TGFA, NRG1, and AREG were up-regulated in HCC827GR. Phosphorylation status of EGFR, HER2, and HER3 was not altered, but that of HER4 was increased in HCC827GR. In HCC827ER, EGFR binding ligands AREG, BTC, and EGF were down-regulated, while phosphorylation of EGFR, HER2, and HRE3 was decreased. However, NRG2 was remarkably elevated and HER4 and its downstream STAT5 were phosphorylated. These results indicate that HER4 and its binding ligands may contribute to acquired resistance to EGFR-TKI. Considering these results, it is possible that the HER4-STAT5 pathway might be common to primary and acquired resistance to EGFR-TKI. We continue to investigate its significance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1906. doi:1538-7445.AM2012-1906