tbuckley/cabot-search huggingface dataset:
Phase II Trial of Bevacizumab Plus Gemcitabine in Patients With Advanced Pancreatic Cancer
Authors: Hedy L. Kindler, Gregory Friberg, Deepti A. Singh, Gershon Locker, Sreenivasa Nattam, Mark Kozloff, David A. Taber, Theodore Karrison, Abraham Dachman, Walter M. Stadler, Everett E. Vokes
Journal: Journal of Clinical Oncology (2005)

Purpose Vascular endothelial growth factor (VEGF) plays a key role in the biology and prognosis of pancreatic cancer. Inhibitors of VEGF suppress the growth of pancreatic cancer in preclinical models. The objectives of this phase II study were to assess the response rate and overall survival of pancreatic cancer patients who received gemcitabine with the recombinant humanized anti-VEGF monoclonal antibody bevacizumab. Patients and Methods Patients with previously untreated advanced pancreatic cancer received gemcitabine 1,000 mg/m 2 intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Bevacizumab, 10 mg/kg, was administered after gemcitabine on days 1 and 15. Tumor measurements were assessed every two cycles. Plasma VEGF levels were obtained pretreatment. Results Fifty-two patients were enrolled at seven centers between November 2001 and March 2004. All patients had metastatic disease, and 83% had liver metastases. Eleven patients (21%) had confirmed partial responses, and 24 (46%) had stable disease. The 6-month survival rate was 77%. Median survival was 8.8 months; median progression-free survival was 5.4 months. Pretreatment plasma VEGF levels did not correlate with outcome. Grade 3 and 4 toxicities included hypertension in 19% of the patients, thrombosis in 13%, visceral perforation in 8%, and bleeding in 2%. Conclusion The combination of bevacizumab plus gemcitabine is active in advanced pancreatic cancer patients. Additional study is warranted. A randomized phase III trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo is ongoing in the Cancer and Leukemia Group B.
How Jackendoff helps us think
Authors: Carlos Molina
Journal: Behavioral and Brain Sciences (2003)

The nature of the relationship between language and thought has been quite elusive. We believe that its understanding is crucially dependent on the available notions of language and thought. Foundations of Language offers an unusually clear and complete account of both, providing a fruitful and much needed framework for future research. No doubt it will help us think better about these elusive complexities.
<i>CHRNA3</i>genotype, nicotine dependence, lung function and disease in the general population
Authors: Diljit Kaur-Knudsen, Børge G. Nordestgaard, Stig E. Bojesen
Journal: European Respiratory Journal (2012)

The CHRNA3 rs1051730 polymorphism has been associated to chronic obstructive pulmonary disease (COPD), lung cancer and nicotine dependence in case–control studies with high smoking exposure; however, its influence on lung function and COPD severity in the general population is largely unknown. We genotyped 57,657 adult individuals from the Copenhagen General Population Study, of whom 34,592 were ever-smokers. Information on spirometry, hospital admissions, smoking behaviour and use of nicotinic replacement therapy was recorded. In homozygous (11%), heterozygous (44%) and noncarrier (45%) ever-smokers, forced expiratory volume in 1 s (FEV 1 ) was 94.1% predicted, 95.3% pred and 96.5% pred, forced vital capacity (FVC) was 97.1% pred, 97.5% pred and 98.3% pred, and FEV 1 /FVC was 0.770, 0.773 and 0.777, respectively (all p&lt;0.001 for trend). Smoking interacted with genotype on FEV 1 % pred and FEV 1 /FVC (both p&lt;0.001). When adjusted for cumulative tobacco consumption, these associations remained significant. In ever-smokers, odds ratios for COPD in homozygotes versus noncarriers were 1.3 (95% CI 1.2–1.4) for Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I–IV, 1.4 (95% CI 1.2–1.6) for GOLD II–IV and 1.7 (95% CI 1.3–2.1) for GOLD III–IV. The corresponding value for lung cancer was 1.8 (95% CI 1.2–2.6). Genotype was also associated with daily and cumulative tobacco consumption and with use of nicotinic replacement therapy in former smokers. In ever-smokers, the CHRNA3 rs1051730 genotype associated with reduced lung function and increased COPD severity.
Endothelial progenitor cells undergo an endothelial-to-mesenchymal transition-like process mediated by TGFβRI
Authors: Marta Díez, Melina M. Musri, Elisabet Ferrer, Joan A. Barberà, Víctor I. Peinado
Journal: Cardiovascular Research (2010)

Endothelial progenitor cells (EPC) have been shown to repair pulmonary endothelium, although they can also migrate into the arterial intima and differentiate into smooth muscle-like (mesenchymal) cells contributing to intimal hyperplasia. The molecular mechanisms by which this process proceeds have not been fully elucidated. Here, we study whether genes involved in the endothelial-to-mesenchymal transition (EnMT) may contribute to the mesenchymal phenotype acquisition of EPC and we evaluate whether transforming growth factor β1 (TGFβ1) is involved in this process. Our results show that co-culture of EPC with smooth muscle cells (SMC) increases the expression of the mesenchymal cell markers α-smooth muscle actin, sm22-α, and myocardin, and decreases the expression of the endothelial cell marker CD31. In the same conditions, we also observed a concomitant increase in the gene expression of the EnMT-related transcription factors: slug, snail, zeb1, and endothelin-1. This indicates that mesenchymal phenotype acquisition occurred through an EnMT-like process. Inhibition of TGFβ receptor I (TGFβRI) downregulated snail gene expression, blocked the EnMT, and facilitated the differentiation of EPC to the endothelial cell lineage. Furthermore, TGFβRI inhibition decreased migration of EPC stimulated by SMC without affecting their functionality and adhesion capacity. These results indicate that EPC may differentiate into SMC-like cells through an EnMT-like process and that TGFβI plays an important role in the fate of EPC.
Influence of C3 Deficiency on Atherosclerosis
Authors: Chiara Buono, Carolyn E. Come, Joseph L. Witztum, Graham F. Maguire, Philip W. Connelly, Michael Carroll, Andrew H. Lichtman
Journal: Circulation (2002)

Background — The influence of complement activation on atherosclerosis is not well understood. The purpose of this study was to examine the effects of C3 deficiency on the extent and phenotype of atherosclerosis. Methods and Results — Aortic atherosclerosis was analyzed in low-density lipoprotein receptor (ldlr)/C3-deficient mice ( ldlr −/− C3 −/− ) and ldlr −/− C3 +/− littermate control mice after 15 weeks on a 1.25% (wt/wt) cholesterol diet. Serum lipoprotein profiles and immunoglobulin levels were not significantly different between the 2 experimental groups. The lipid-positive en face lesional area in thoracic and abdominal aorta was greater in C3-deficient mice than in control mice (3.9% versus 2.1%, median, P =0.0076). Similarly , the lipid-positive area in aortic arch sections was greater in C3-deficient mice than in controls (0.04 mm 2 versus 0.02 mm 2 , median, P =0.0089). Analysis of aortic arch sections showed greater lesional macrophage content in C3-deficient versus control mice (8.24±1.36% versus 5.9±1.63% intimal area, mean±SEM, P =0.003), less smooth muscle cell content in C3-deficient versus control mice (0.06±0.05% versus 0.92±0.32% intimal area, mean±SEM, P &lt;0.0001), and less collagen content in C3-deficient versus control mice (0.52±1.26% versus 11±10.43% intimal area, mean±SEM, P =0.008). Conclusions — The maturation of atherosclerotic lesions beyond the foam cell stage is strongly dependent on an intact complement system.
BCG and infection with Mycobacterium tuberculosis
Authors: R. D. Turner, C. D. Tweed, J. Shukla, G. H. Bothamley
Journal: Thorax (2014)

Michelsen and colleagues1 usefully add to the evidence for the protective effect of BCG against active TB. However, we are puzzled by the conclusion that BCG also prevents Mycobacterium tuberculosis (Mtb) infection. Others have similarly used interferon gamma release assay (IGRA) responses as a surrogate for Mtb infection with similar conclusions.2 ,3

A positive IGRA response represents a previous interaction with Mtb that was sufficient to lead to an acquired immune response. The authors demonstrate a reduced incidence of IGRA response in individuals vaccinated with BCG despite continued risk of Mtb exposure.

The authors’ hypothesis that …
Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis
Authors: T Pincus
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Acetaminophen (paracetamol) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis. However, survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors. <b>Design:</b> Two randomised, double blind, placebo controlled, crossover multicentre clinical trials, Patient Preference for Placebo, Acetaminophen or Celecoxib Efficacy Studies (PACES). <b>Patients:</b> Osteoarthritis of knee or hip. <b>Intervention:</b> "Wash out" of treatment; randomisation; 6 weeks of celecoxib 200 mg/day, acetaminophen 1000 mg four times a day, or placebo; second "wash out;" crossover to 6 weeks of second treatment. <b>Measurements:</b> Western Ontario McMaster Osteoarthritis Index (WOMAC), visual analogue pain scale, patient preference between two treatments. <b>Results:</b> Celecoxib was more efficacious than acetaminophen in both periods in both studies; WOMAC and pain scale scores differed at p&lt;0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b, but not in period I of PACES-a. Acetaminophen was more efficacious than placebo, generally p&lt;0.05 in PACES-b, and &gt;0.05 in PACES-a. Patient preferences were 53% celecoxib <i>v</i> 24% acetaminophen in PACES-a (p&lt;0.001) and 50% <i>v</i> 32% in PACES-b (p = 0.009); 37% acetaminophen <i>v</i> 28% placebo in PACES-a (p = 0.340) and 48% <i>v</i> 24% in PACES-b (p = 0.007). No clinically or statistically significant differences were seen in adverse events or tolerability among the three treatment groups. <b>Conclusions:</b> Greater efficacy was seen for celecoxib <i>v</i> acetaminophen <i>v</i> placebo, while adverse events and tolerability were similar. Variation in results and statistical significance in the two different trials are of interest.
The Case for Individualized Screening Recommendations for Breast Cancer
Authors: Angela Bradbury, Olufumilayo I. Olopade
Journal: Journal of Clinical Oncology (2006)

typesofcancer,includingbreastcancer. 2-4 Thelinkbetweenbreast cancer and lower levels of radiation, such as those in diagnostic chest x-rays, computed tomography 5 scans, or mammograms, remains controversial. Studies to date suggest some excess risk even with low levels of radiation exposure, although the magnitude is ill defined. 4 Annual mammography is currently the cornerstone of breast cancer surveillance and has been shown to provide a mortality benefit for women over the age of 40 years old. 6 Thus, the benefits of mammographic screening outweigh the risks for women of average risk over the age of 40 years old. Epidemiologic studieshaveconsistentlydescribedahigherriskofbreastcancerfor womenexposedtoatomicandmedicalirradiationbeforetheageof 20 years old, 2-4 and it seems that there is little to no increased risk with exposure after the age of 50 years old. 2 It is likely that the impactofradiation-associatedbreastcancerissmalltononexistent among women who begin standard mammographic screening at 40 years old, but we do not know if this is also the case for women at high genetic risk.
A Comprehensive Overview of the Vertebrate p24 Family: Identification of a Novel Tissue-Specifically Expressed Member
Authors: J. R.P.M. Strating, N. H.M. van Bakel, J. A.M. Leunissen, G. J.M. Martens
Journal: Molecular Biology and Evolution (2009)

The members of the p24 protein family have an important but unclear role in transport processes in the early secretory pathway. The p24 family consists of four subfamilies (α, β, γ, and δ), whereby the exact composition of the family varies among species. Despite more than 15 years of p24 research, the vertebrate p24 family is still surprisingly ill characterized. Here, we describe the human, mouse, Xenopus, and zebrafish orthologues of 10 p24 family members and a new member that we term p24γ5. Of these eleven p24 family members, nine are conserved throughout the vertebrate lineage, whereas two (p24γ4 and p24δ2) occur in some but not all vertebrates. We further show that all p24 proteins are widely expressed in mouse, except for p24α1 and p24γ5 that display restricted expression patterns. Thus, we present for the first time a comprehensive overview of the phylogeny and expression of the vertebrate p24 protein family.
Probiotics in IBD
Authors: R J KENNEDY
Journal: Gut (2001)

Editor,—We read with interest the therapy update by Shanahan ((2001) Gut 48:609–609; [OpenUrl][1][CrossRef][2][PubMed][3]). This is an excellent summary of the potential role of bacteria both in the pathogenesis and treatment of inflammatory bowel disease (IBD). The author is correct in stating that our knowledge of the composition … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BParenteral%2Band%2BEnteral%2BNutrition%26rft.stitle%253DJPEN%2BJ%2BParenter%2BEnteral%2BNutr%26rft.aulast%253DKennedy%26rft.auinit1%253DR.J.%26rft.volume%253D24%26rft.issue%253D3%26rft.spage%253D189%26rft.epage%253D195%26rft.atitle%253DPromotion%2Bof%2Ba%2BFavorable%2BGut%2BFlora%2Bin%2BInflammatory%2BBowel%2BDisease%26rft_id%253Dinfo%253Adoi%252F10.1177%252F0148607100024003189%26rft_id%253Dinfo%253Apmid%252F10850949%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1177/0148607100024003189&link_type=DOI [3]: /lookup/external-ref?access_num=10850949&link_type=MED&atom=%2Fgutjnl%2F49%2F6%2F873.2.atom
Targeting Plasma Cells in Autoimmune Diseases
Authors: David M. Tarlinton, Philip D. Hodgkin
Journal: The Journal of Experimental Medicine (2004)

Antibodies specific for self-antigens mediate life-threatening pathology in several autoimmune diseases. Clearly the ability to target the plasma cells (PCs) producing the autoantibodies would be of great clinical benefit. Current immunosuppressive therapies are based on the premise that autoreactive PCs are short-lived and replenished from ongoing immune responses. However, recent results question this assumption and suggest that optimizing the treatment of severe autoimmune conditions will require a significant investment in elucidating the details of PC biology.
Behavioral Science Research in the Prevention of Diabetes
Authors: Edwin B. Fisher, Elizabeth A. Walker, Ann Bostrom, Baruch Fischhoff, Debra Haire-Joshu, Suzanne Bennett Johnson
Journal: Diabetes Care (2002)

Recent studies show diabetes can be prevented. Growing knowledge of its biological bases opens further prevention opportunities. This article focuses on behavioral science research that may advance these opportunities. An ecological model guides attention to how prevention research may be pursued at the individual, group, or community levels. Three key areas are reviewed: risk communication, screening, and preventive interventions. Research on diabetes risk communication is limited but suggests that many are relatively unaware of risks and may have misconceptions about the disease. Amid policy debates and research regarding the potential benefits and costs of screening, identification of diabetes may itself be risky in terms of psychological and social consequences. The Diabetes Prevention Program and other studies make clear that diabetes can be prevented, both by the combination of weight loss and physical activity and by medications. Research needs to address promoting these methods to individuals as well as to groups and even whole communities. Fundamental as well as applied research should address how risks of diabetes are understood and may be communicated; how to enhance benefits and minimize psychological and other risks of screening; how to promote healthy eating and weight loss, physical activity, and appropriate use of medications to prevent diabetes; and how to reduce socioeconomic and cultural disparities in all these areas.
OBSERVATIONS ON THE PHAGOCYTOSIS OF THE PNEUMOCOCCUS BY HUMAN WHOLE BLOOD
Authors: Hugh K. Ward
Journal: The Journal of Experimental Medicine (1930)

1. In vitro phagocytic experiments with human blood, antipneumococcus serum, pneumococcus specific soluble substance, and living virulent pneumococci show that there is a definite phagocytic inhibition zone when strong antiserum is used. 2. If the antiserum is further diluted, there is a zone where phagocytosis is effective. If the serum is diluted still more, phagocytosis gradually falls off, as the very dilute antiserum fails to neutralize the specific carbohydrate, which has a specific antiphagocytic action. 3. The inhibition zone is apparently caused by the specific precipitate (formed by the antiserum and the specific carbohydrate) interfering, perhaps mechanically, with the ingestion of the pneumococci by the leucocytes. 4. The inhibition zone is better marked with Type III than with Type I pneumococcus. 5. As the concentration of antiserum in the zone of effective phagocytosis in vitro does not correspond with the concentration of antiserum generally used in vivo in the serum therapy of pneumonia, this question is discussed.
Effects of Brain Evolution on Human Nutrition and Metabolism
Authors: William R. Leonard, J. Josh Snodgrass, Marcia L. Robertson
Journal: Annual Review of Nutrition (2007)

The evolution of large human brain size has had important implications for the nutritional biology of our species. Large brains are energetically expensive, and humans expend a larger proportion of their energy budget on brain metabolism than other primates. The high costs of large human brains are supported, in part, by our energy- and nutrient-rich diets. Among primates, relative brain size is positively correlated with dietary quality, and humans fall at the positive end of this relationship. Consistent with an adaptation to a high-quality diet, humans have relatively small gastrointestinal tracts. In addition, humans are relatively "undermuscled" and "over fat" compared with other primates, features that help to offset the high energy demands of our brains. Paleontological evidence indicates that rapid brain evolution occurred with the emergence of Homo erectus 1.8 million years ago and was associated with important changes in diet, body size, and foraging behavior.
Varicocoele caused by a pancreatic pseudocyst.
Authors: J M Dixon, C P Armstrong, O Eremin
Journal: Gut (1983)

Pseudocysts of the pancreas, when large, can compress adjacent structures giving rise to a series of clinical symptoms and signs. We present a patient whose pseudocyst compressed the left renal and testicular veins, resulting in a left sided varicocoele. We can find no evidence of such a complication having been previously reported.
Fulminant EBV+ T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome
Authors: Leticia Quintanilla-Martinez, Shimareet Kumar, Falko Fend, Edgardo Reyes, Julie Teruya-Feldstein, Douglas W. Kingma, Lynn Sorbara, Mark Raffeld, Stephen E. Straus, Elaine S. Jaffe
Journal: Blood (2000)
<i>In vivo</i>assessment of lung inflammatory cell activity in patients with COPD and asthma
Authors: H.A. Jones, P.S. Marino, B.H. Shakur, N.W. Morrell
Journal: European Respiratory Journal (2003)

The involvement of inflammatory cells in the pathogenesis of chronic obstructive pulmonary disease (COPD) and asthma is well established. This study aimed to quantify differences in inflammatory cell function in situ in these patients as compared to normal subjects. Positron emission tomography was used to assess neutrophil activity ( 18 F-fluorodeoxyglucose ( 18 FDG)) and macrophage accumulation ( 11 C-PK11195) in six patients with COPD, six chronic asthmatics and five age-matched normal control subjects. 18 FDG uptake was greater in COPD than in normal subjects, with no increase in asthmatics. The mean slope of 18 FDG uptake, corrected for volume of distribution, was 4.0 min −1 in COPD patients compared with 1.5 min −1 in control subjects and 1.7 min −1 in asthmatics. Mean 11 C-PK11195 uptake (plateau tissue:plasma) was higher in four of six COPD patients (10.8) and three of five asthmatics (11.8) than the maximum value in control subjects (6.2). From this preliminary study the authors conclude that positron emission tomography may be useful to assess polymorphonuclear neutrophil and macrophage activity in vivo in chronic obstructive pulmonary disease and asthma, and may reveal differences in cell behaviour between the study groups. In addition, positron emission tomography may provide indices of disease activity for future therapeutic studies.
Hematopoietic stem cell transplantation for infantile osteopetrosis
Authors: Paul J. Orchard, Anders L. Fasth, Jennifer Le Rademacher, Wensheng He, Jaap Jan Boelens, Edwin M. Horwitz, Amal Al-Seraihy, Mouhab Ayas, Carmem M. Bonfim, Farid Boulad, Troy Lund, David K. Buchbinder, Neena Kapoor, Tracey A. O’Brien, Miguel A. Diaz Perez, Paul A. Veys, Mary Eapen
Journal: Blood (2015)
B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new "speed congenic" stock of NOD.Ig mu null mice.
Authors: D V Serreze, H D Chapman, D S Varnum, M S Hanson, P C Reifsnyder, S D Richard, S A Fleming, E H Leiter, L D Shultz
Journal: The Journal of Experimental Medicine (1996)

The T lymphocytes mediating autoimmune destruction of pancreatic beta cells in the nonobese diabetic (NOD) mouse model of insulin-dependent diabetes mellitus (IDDM) may be generated due to functional defects in hematopoietically derived antigen-presenting cells (APC). However, it has not been clear which particular subpopulations of APC (B lymphocytes, macrophages, and dendritic cells) contribute to the development and activation of diabetogenic T cells in NOD mice. In the current study we utilized a functionally inactivated immunoglobulin (Ig) mu allele (Ig mu null) to generate a "speed congenic" stock of B lymphocyte-deficient NOD mice that are fixed for linkage markers delineating previously identified diabetes susceptibility (Idd) genes. These B lymphocyte NOD.Ig mu null mice had normal numbers of T cells but were free of overt IDDM and insulitis resistant, while the frequency of disease in the B lymphocyte intact segregants was equivalent to that of standard NOD mice in our colony. Thus, B lymphocytes play a heretofore unrecognized role that is essential for the initial development and/or activation of beta cell autoreactive T cells in NOD mice.