tbuckley/cabot-search huggingface dataset:
Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N.
Authors: A T Look, R A Ashmun, L H Shapiro, S C Peiper
Journal: Journal of Clinical Investigation (1989)

To determine the primary structure of CD13, a 150-kD cell surface glycoprotein originally identified on subsets of normal and malignant human myeloid cells, we isolated the complete sequences encoding the polypeptide in overlapping complementary DNA (cDNA) clones. The authenticity of our cDNA clones was demonstrated by the ability of the coding sequences, subcloned in a retroviral expression vector, to mediate expression of bona fide CD13 molecules at the surface of transfected mouse fibroblasts. The nucleotide sequence predicts a 967 amino acid integral membrane protein with a single, 24 amino acid hydrophobic segment near the amino terminus. Amino-terminal protein sequence analysis of CD13 molecules indicated that the hydrophobic segment is not cleaved, but rather serves as both a signal for membrane insertion and as a stable membrane-spanning segment. The remainder of the molecule consists of a large extracellular carboxyterminal domain, which contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloprotease superfamily. Sequence comparisons with known enzymes of this class revealed that CD13 is identical to aminopeptidase N, a membrane-bound glycoprotein thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes prepared from cells of the central nervous system.
The Diagnosis and Management of Mild Cognitive Impairment
Authors: Kenneth M. Langa, Deborah A. Levine
Journal: JAMA (2014)

<h3>Importance</h3> Cognitive decline is a common and feared aspect of aging. Mild cognitive impairment (MCI) is defined as the symptomatic predementia stage on the continuum of cognitive decline, characterized by objective impairment in cognition that is not severe enough to require help with usual activities of daily living. <h3>Objective</h3> To present evidence on the diagnosis, treatment, and prognosis of MCI and to provide physicians with an evidence-based framework for caring for older patients with MCI and their caregivers. <h3>Evidence Acquisition</h3> We searched PubMed for English-language articles in peer-reviewed journals and the Cochrane Library database from inception through July 2014. Relevant references from retrieved articles were also evaluated. <h3>Findings</h3> The prevalence of MCI in adults aged 65 years and older is 10% to 20%; risk increases with age and men appear to be at higher risk than women. In older patients with MCI, clinicians should consider depression, polypharmacy, and uncontrolled cardiovascular risk factors, all of which may increase risk for cognitive impairment and other negative outcomes. Currently, no medications have proven effective for MCI; treatments and interventions should be aimed at reducing cardiovascular risk factors and prevention of stroke. Aerobic exercise, mental activity, and social engagement may help decrease risk of further cognitive decline. Although patients with MCI are at greater risk for developing dementia compared with the general population, there is currently substantial variation in risk estimates (from &lt;5% to 20% annual conversion rates), depending on the population studied. Current research targets improving early detection and treatment of MCI, particularly in patients at high risk for progression to dementia. <h3>Conclusions and Relevance</h3> Cognitive decline and MCI have important implications for patients and their families and will require that primary care clinicians be skilled in identifying and managing this common disorder as the number of older adults increases in coming decades. Current evidence supports aerobic exercise, mental activity, and cardiovascular risk factor control in patients with MCI.
Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of Helicobacter pylori
Authors: Marco Romano, Riccardo Marmo, Antonio Cuomo, Teresa De Simone, Caterina Mucherino, Maria Rosaria Iovene, Fortunato Montella, Maria Antonietta Tufano, Camillo Del Vecchio Blanco, Gerardo Nardone
Journal: Clinical Gastroenterology and Hepatology (2003)
Adjuvant Therapy in Rectal Cancer: Analysis of Stage, Sex, and Local Control—Final Report of Intergroup 0114
Authors: J.E. Tepper, M. O’Connell, D. Niedzwiecki, D.R. Hollis, A.B. Benson, B. Cummings, L.L. Gunderson, J.S. Macdonald, J.A. Martenson, R.J. Mayer
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure. PATIENTS AND METHODS: All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy. RESULTS: One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females. CONCLUSION: There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy.
The effect of radical treatment and pulmonary rehabilitation on muscle mass as measured with CT-scan: A randomised trial in patients (pts) with lung cancer and mesothelioma
Authors: Bihiyga Salhi, Gilles Thysebaert, Thomas L. Malfait, Karim Vermaelen, Veerle F. Surmont, Wouter Huysse, Georges Van Maele, Jan P. van Meerbeeck, Eric Derom
Journal: European Respiratory Journal (2012)

Introduction: Cancer and its treatment are known to contribute to fatigue and functional impairment.The latter is thought to result from loss of muscle mass and strength. Aim: To investigate the effect of radical treatment and post-treatment rehabilitation on muscle mass and strength in pts with thoracic cancer. Methods: Muscle mass was estimated with the fat free mass (FFM) by bioelectrical impedance and the cross-sectional area (CSA) of skeletal muscle on a single 10-mm CT-scan slice. Muscle strength was estimated by the quadriceps force (QF).All variables were measured pre-treatment (M1), after radical treatment (M2) and after either 12w of rehabilitation (RA) or control (CON) (M3). Data are presented as medians with 95% CI. Results: Of 29 consecutive pts, 18 were allocated to RA and 11 to CON. Both groups have comparable M1 characteristics. At M2, all pts showed a significant decrease in muscle mass and strength. At M3, only RA-patients improved significantly their muscle mass. There is a good correlation between muscle CSA and FFM (r: 0.70; p <0.001). Conclusion: Muscle mass and strength significantly decrease with radical treatment in pts with lung cancer and mesothelioma. Muscle mass increases with rehabilitation. CT scan can substitute bioelectrical impedance for measuring muscle mass. Mature data will be presented at the meeting.

![Figure][1]  [1]: pending:yes
Y chromosome variation of mice and men
Authors: M. W. Nachman
Journal: Molecular Biology and Evolution (1998)

DNA sequences from the nonrecombining portion of the Y chromosome were compared with autosomal and X-linked sequences from mice and humans to test the neutral prediction that ratios of polymorphism to divergence are the same for different genes. Intraspecific variation within Mus domesticus was compared with divergence between M. domesticus and Mus caroli for Sry, a region 5' to Sry, and four X-linked genes, Hprt, Plp, Amg, and Glra2. None of these comparisons revealed significantly reduced variation on the Y chromosome. Intraspecific variation within humans was compared with divergence between humans and chimpanzees for three Y-linked loci (Zfy, the YAP region, and the Sry region), seven X-linked loci (Il2rg, Plp, Hprt, Gk, Ids, Pdhal, and Dmd), and the beta-globin locus on chromosome 11. In these comparisons, the observed level of variation on the human Y chromosome was slightly lower than expected, but was significantly lower in only one case (Sry region vs. Dmd). These results suggest that the levels of variability on the Y chromosome in mice and humans are close to expected values given the effective population size and mutation rates for these loci. There is at most only a modest reduction in variability that may be attributed to natural selection (either genetic hitchhiking or background selection).
Vaccine with β-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses
Authors: Xiao-Tong Ma, Bin Xu, Li-Li An, Cheng-Ya Dong, Yong-Min Lin, Yang Shi, Ke-Fu Wu
Journal: Cancer Research (2006)

Abstract Murine β-defensin 2 (MBD2) is a small antimicrobial peptide of the innate immune system. Recent study showed that MBD2 could not only recruit immature dendritic cells but also activate them by Toll-like receptor 4 and thus may provide a critical link between the innate immune system and the adaptive immune response. In this report, we examined the antileukemia activity of MBD2 in a murine model of acute lymphoid leukemia (ALL) L1210. L1210 cells were engineered to secrete biologically functional MBD2. MBD2-modified L1210 (L1210-MBD2) showed significantly reduced leukemogenecity, resulting in a 80% rate of complete leukemia rejection. Inoculation of mice with L1210-MBD2 induced enhanced CTL and natural killer (NK) activity and augmented interleukin-12 and IFN-γ production. All the recovered mice from the inoculation showed a protective immunity to the following challenge with parental L1210 cells and generate leukemia-specific memory CTL. Vaccines with irradiated L1210-MBD2 cells could cure 50% leukemia-bearing mice. Depletion of CD8+ T cells but not CD4+ T cells completely abrogated the antileukemia activity of MBD2. Interestingly, NK cells were also required for the MBD2-mediated antileukemia response, although ALL generally display a high degree of resistance to NK-mediated lysis. Our results suggest that MBD2 can activate both innate and adaptive immunity to generate potent antileukemia response, and MBD2 immunotherapy warrants further evaluation as a potential treatment for ALL. (Cancer Res 2006; 66(2): 1169-76)
RELATION BETWEEN EPSTEIN-BARR VIRAL AND CELL MEMBRANE IMMUNOFLUORESCENCE IN BURKITT TUMOR CELLS
Authors: G. Klein, G. Pearson, G. Henle, W. Henle, G. Goldstein, P. Clifford
Journal: The Journal of Experimental Medicine (1969)

Sera from patients with Burkitt's lymphoma (BL), infectious mononucleosis (IM), carcinoma of the postnasal space (Ca PNS), and various controls were investigated for antibodies against the Epstein-Barr virus (EBV) by immunofluorescence on acetone-fixed smears (5) and for antibodies against the distinctive antigenic sites expressed on the surface of viable lymphoblastoid cells within EBV-carrying culture lines (1). The latter were studied by the blocking of direct membrane staining with FITC-conjugated Mutua serum. This serum has been derived from a Burkitt's lymphoma patient in long-term regression after chemotherapy and is free from detectable isoantibodies. It has been used previously as a standard of reference to demonstrate the presence of the membrane antigen(s) on all lines derived from BL biopsies and leukocytes from IM patients. It was found that 102 of 279 (37%) of the sera tested had high anti-EBV titers (>==80) and high membrane-blocking (Bl > 0.5) activity, 124 of 279 (44%) of the sera were low in both tests, 22 of 279 (8%) had low EBV titers (<==80), in spite of a high blocking index, and 31 of 279 (11%) of the sera were low in blocking activity (<0.5), in spite of a high EBV titer. The two tests thus gave concordant results with 81% and discordant with 19% of the sera. The majority of sera from BL patients were high in both tests. IM sera also showed a relationship between the two antibody activities but, in general, both activities were lower than in BL cases. Ca PNS sera seemed to fall into two main groups: (a) high anti-EBV, high blocking or (b) low anti-EBV, low blocking. Control sera, including four isoantisera, showed predominantly low reactivities in both tests.
Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial
Authors: Paulus Kirchhof, Dietrich Andresen, Ralph Bosch, Martin Borggrefe, Thomas Meinertz, Ulli Parade, Ursula Ravens, Alexander Samol, Gerhard Steinbeck, Andras Treszl, Karl Wegscheider, Günter Breithardt
Journal: The Lancet (2012)
Divergence in Tumor Induction of Thymus Cells Transformed &lt;italic&gt;In Vitro&lt;/italic&gt; by Gross Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Harry L. Ioachim
Journal: JNCI Journal of the National Cancer Institute (1969)
Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients
Authors: C Collen, N Christian, D Schallier, M Meysman, M Duchateau, G Storme, M De Ridder
Journal: Annals of Oncology (2014)

Stereotactic body radiotherapy (SBRT) has emerged as a treatment modality in patients presenting with oligometastatic nonsmall-cell lung cancer (NSCLC). SBRT is used as a local consolidative treatment to metastatic disease sites. The majority of patients included in SBRT trials for oligometastatic NSCLC have controlled primary tumors and brain metastases.Oligometastatic NSCLC patients with ≤5 metastatic lesions were included in a prospective phase II trial to evaluate efficacy and toxicity of SBRT to all disease sites, primary tumor and metastatic locations. SBRT to a dose of 50 Gy in 10 fractions was delivered. Positron emission tomography-computed tomography (PET-CT) was carried out at baseline and 3 months after SBRT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST). The progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier method from start of chemotherapy or radiotherapy. Side-effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.Twenty-six patients received SBRT after induction chemotherapy (n = 17) or as a primary treatment (n = 9). Median follow-up was 16.4 months. Overall metabolic response rate was 60% with seven patients (30%) achieving a complete metabolic remission and 7 (30%) a partial metabolic response. Any acute grade 2 toxicity was observed in four patients (15%) and grade 3 pulmonary toxicity in two patients (8%). Median PFS and OS were 11.2 and 23 months. The 1-year PFS and 1-year OS rate were 45% and 67%, respectively.SBRT to all disease sites, primary tumor and metastatic locations, in oligometastatic NSCLC patients produced an acceptable median PFS of 11.2 months.
Talc mediates angiostasis in malignant pleural effusions via endostatin induction
Authors: N. Najmunnisa, K. A. Mohammed, S. Brown, Y. Su, P. S. Sriram, B. Moudgil, R. Loddenkemper, V. B. Antony
Journal: European Respiratory Journal (2007)

Talc remains the most effective sclerosing agent for pleurodesis. However, its mechanism of action in resolving pleural malignant disease remains unclear. The present study evaluated the angiogenic balance in the pleural space in patients with malignant pleural effusions (MPE) following talc insufflation. Patient pleural fluid samples were collected both before and after talc insufflation. The ability of pleural mesothelial cells (PMC) and malignant mesothelioma cells (MMC) to produce endostatin in vitro was compared. The biological effects of pleural fluids and conditioned media from talc-activated PMC on endothelial cells were evaluated by performing proliferation, invasion, tube formation and apoptosis assays. Pleural fluids from patients with MPE who received thoracoscopic talc insufflation contained significantly higher levels of endostatin (median 16.75 ng·mL −1 ) compared with pre-talc instillation (1.06 ng·mL −1 ). Talc-activated PMC released significantly greater amounts of endostatin (mean± sem 1052.39±38.66 pg·mL −1 ) when compared with a MMC line (134.73±8.72 pg·mL −1 ). In conlusion, talc alters the angiogenic balance in the pleural space from a biologically active and angiogenic environment to an angiostatic milieu. Functional improvement following talc poudrage in patients with malignant pleural effusions may, in part, reflect these alterations in the pleural space.
A role for leukocyte-endothelial adhesion mechanisms in epilepsy
Authors: Paolo F Fabene, Graciela Navarro Mora, Marianna Martinello, Barbara Rossi, Flavia Merigo, Linda Ottoboni, Simona Bach, Stefano Angiari, Donatella Benati, Asmaa Chakir, Lara Zanetti, Federica Schio, Antonio Osculati, Pasquina Marzola, Elena Nicolato, Jonathon W Homeister, Lijun Xia, John B Lowe, Rodger P McEver, Francesco Osculati, Andrea Sbarbati, Eugene C Butcher, Gabriela Constantin
Journal: Nature Medicine (2008)
Mitochondrial Genetics Regulate Breast Cancer Tumorigenicity and Metastatic Potential
Authors: Kyle P. Feeley, Alexander W. Bray, David G. Westbrook, Larry W. Johnson, Robert A. Kesterson, Scott W. Ballinger, Danny R. Welch
Journal: Cancer Research (2015)

Abstract Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors influence an individual's predilection for developing metastatic breast cancer. Investigations of tumor latency and metastasis in mice have illustrated differences between inbred strains, but the possibility that mitochondrial genetic inheritance may contribute to such differences in vivo has not been directly tested. In this study, we tested this hypothesis in mitochondrial–nuclear exchange mice we generated, where cohorts shared identical nuclear backgrounds but different mtDNA genomes on the background of the PyMT transgenic mouse model of spontaneous mammary carcinoma. In this setting, we found that primary tumor latency and metastasis segregated with mtDNA, suggesting that mtDNA influences disease progression to a far greater extent than previously appreciated. Our findings prompt further investigation into metabolic differences controlled by mitochondrial process as a basis for understanding tumor development and metastasis in individual subjects. Importantly, differences in mitochondrial DNA are sufficient to fundamentally alter disease course in the PyMT mouse mammary tumor model, suggesting that functional metabolic differences direct early tumor growth and metastatic efficiency. Cancer Res; 75(20); 4429–36. ©2015 AACR.
Safety of tiotropium through the Handihaler: why did meta-analyses and database studies appear to give a false alarm?
Authors: Neil C Barnes, Paul W Jones, Kourtney J Davis
Journal: Thorax (2014)

Concerns about the safety of long-acting antimuscarinic agents for the treatment of COPD,1 ,2 particularly the use of tiotropium through the Respimat device, led to the TIOSPIR study.3 This large well-conducted randomised study compared the use of tiotropium through the Handihaler (18 µg) with tiotropium at two doses (2.5 µg and 5.0 µg) through the Respimat in over 17 000 patients with COPD. It showed no difference in mortality or efficacy between the two delivery systems, nor even a trend for a mortality difference. It is now worth reviewing the data that led to these concerns and the lessons that may be learned.

Two systematic reviews played a key role in raising concerns over tiotropium. Antimuscarinic agents were generally considered safe and well tolerated until a meta-analysis of trials that included short-acting and long-acting antimuscarinic agents suggested an increase in cardiac events and mortality.1 This led to fears about safety of the whole class, although the analysis was criticised because it combined short-acting and long-acting antimuscarinic agents. Concerns about tiotropium via the Handihaler were addressed by the UPLIFT study4 a large randomised double-blind placebo-controlled trial which compared the addition of tiotropium or placebo to routine treatment for COPD over a 4-year period. Although the primary outcome was rate of decline of lung function, data on deaths and cardiac side effects were collected prospectively. There was a numerical reduction in mortality in the tiotropium-treated group, which in the prespecified statistical evaluation did not reach statistical significance. There was also evidence of a reduction in reported cardiac events in the actively treated group. This led to the view that tiotropium through the Handihaler did not cause an excess of cardiac adverse events. The results were reviewed by the Regulatory Agencies who were in agreement with this.5

Following this, a …
The 'USHealth Act'
Authors: Rep Edward R. Roybal
Journal: JAMA (1991)

MUCH to the credit of The Journal and its editors, this in-depth discussion is significant in its timeliness. It should be a precursor to action. Having just passed the largest federal deficit reduction package in the history of this nation, the federal government is in a position to tackle the societal problems that have seemed so intractable for so long. One of the most intractable problems has been caring for the health of the uninsured and underinsured, the theme of this issue ofThe Journal. As this issue makes its way to hundreds of thousands of key decision makers in and outside of the medical community, it is crucial that ever larger portions of that community become actively committed to comprehensive reform and to helping ensure that the terms "uninsured and underinsured Americans" will be removed from the American health care vocabulary. <h3>THE ENVIRONMENT FOR CHANGE</h3> Why this great need
Mobile health use in low- and high-income countries: an overview of the peer-reviewed literature
Authors: Andrew Bastawrous, Matthew J Armstrong
Journal: Journal of the Royal Society of Medicine (2013)

The evolution of mobile phone technology has introduced new possibilities to the field of medicine. Combining technological advances with medical expertise has led to the use of mobile phones in all healthcare areas including diagnostics, telemedicine, research, reference libraries and interventions. This article provides an overview of the peer -reviewed literature, published between 1 August 2006 and 1 August 2011, for the application of mobile/cell phones (from basic text-messaging systems to smartphones) in healthcare in both resource-poor and high-income countries. Smartphone use is paving the way in high-income countries, while basic text-messaging systems of standard mobile phones are proving to be of value in low- and middle-income countries. Ranging from infection outbreak reporting, anti-HIV therapy adherence to gait analysis, resuscitation training and radiological imaging, the current uses and future possibilities of mobile phone technology in healthcare are endless. Multiple mobile phone based applications are available for healthcare workers and healthcare consumers; however, the absolute majority lack an evidence base. Therefore, more rigorous research is required to ensure that healthcare is not flooded with non-evidence based applications and is maximized for patient benefit.