tbuckley/cabot-search huggingface dataset:
Elevated Serum B-Lymphocyte Stimulator Levels in Patients With Familial Lymphoproliferative Disorders
Authors: Anne J. Novak, Deanna M. Grote, Steven C. Ziesmer, Michael P. Kline, Michelle K. Manske, Susan Slager, Thomas E. Witzig, Tait Shanafelt, Timothy G. Call, Neil E. Kay, Diane F. Jelinek, James R. Cerhan, Jane A. Gross, Brandon Harder, Stacey R. Dillon, Stephen M. Ansell
Journal: Journal of Clinical Oncology (2006)

Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease.Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis.We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004).Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.
Abstract P438: Cardiovascular Health in Adolescents with Type 1 Diabetes: The SEARCH CVD Study
Authors: Amy Alman, Jennifer Talton, Ralph D'Agostino, Elizabeth Mayer-Davis, Lawrence Dolan, Elaine Urbina, Santica Marcovina, R. Paul Wadwa, Stephen Daniels, Richard Hamman, Dana Dabelea
Journal: Circulation (2013)

In 2010, the American Heart Association (AHA) identified national goals for ideal cardiovascular health (ICH). Type 1 diabetes (T1D) significantly increases the risk of cardiovascular disease (CVD), and adolescents with T1D are a group particularly relevant for focus on ICH. The purpose of this study was to examine the prevalence of ICH in a population of adolescents with T1D and to examine the association of ICH with measures of CV function [arterial stiffness (AS) measured using pulse-wave velocity (PWV), augmentation index (AIX) and brachial distensibility (BD)], and structure [carotid intima-media thickness (cIMT; bulb, common carotid (CC), and internal carotid (IC))]. We used data from the retrospective cohort component of the SEARCH CVD study, which followed youth with T1D for approximately 6 years. Data collected at baseline (mean age 15 years) include diet, smoking, physical activity, BMI, cholesterol, blood pressure, and fasting plasma glucose. Measures of PWV, AIX, BD, and cIMT were obtained at follow-up (mean age 20 years, diabetes duration 10 years). Complete data were available on 182 subjects. Multiple linear regression models were fit to examine the association between the Number of metrics that met the ICH goal (NICH; range 0 to 7) and the subclinical CVD outcomes. The prevalence of the ICH metrics is shown in Table 1. Prevalence of ICH ranges from none meeting the healthy diet to nearly all being never smokers (88%). While most youth met 3 or 4 goals, only 5% met 5 and none met all 7 criteria. Increasing NICH at baseline was associated with lower AS [lower PWV (β= -0.02, p=0.035), higher BD (β= 0.03, p=0.042)] and lower cIMT of the CC (β= -0.02, p=0.023), adjusted for age, sex, race, hemoglobin A1c, triglycerides, and diabetes duration. In conclusion, youth with T1D are not meeting ICH goals. Meeting more ICH goals was associated with better CV health as indicated by lower AS and cIMT thickness. Measures targeted at increasing ICH in adolescents with T1D are needed in order to reduce the burden of CVD in this high risk population.
Membrane Macrophage Colony-Stimulating Factor on MADB106 Breast Cancer Cells Does Not Activate Cytotoxic Macrophages but Immunizes Rats against Breast Cancer
Authors: Christopher C. Williams, Hao Trinh, Thanh-Van Tran, Qinghong Dan, Ramon Sanchez, Christina Delgado, Yijun Chen, Brian Sippel, Edward W.B. Jeffes, H.Terry Wepsic, Martin R. Jadus
Journal: Molecular Therapy (2001)

<h2>Abstract</h2> Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.
Laminin and vascular proliferation in rheumatoid arthritis.
Authors: D L Scott, M Salmon, C J Morris, A C Wainwright, K W Walton
Journal: Annals of the Rheumatic Diseases (1984)

Laminin is a high molecular weight basement membrane structural glycoprotein. In rheumatoid arthritis and other arthropathies immunoreactive laminin was prominent in synovial blood vessel basement membranes and acted as a marker for them. It codistributed with collagen type IV. Immunohistological reactivity to laminin showed extensive vascular proliferation in rheumatoid arthritis together with basement membrane reduplication, which was confirmed ultrastructurally. Parallel histological studies showed vascular proliferation was predominantly in the subintimal rheumatoid synovium, where it was related to connective tissue proliferation but not to the inflammatory cell infiltrate. Vascular proliferation was also seen in relation to connective tissue changes in biopsies from cases of haemophilic arthritis, osteoarthritis, and meniscal tears. We suggest connective tissue activation is non-specific reaction associated with vascular proliferation. This involves laminin and other structural proteins. It occurs in rheumatoid arthritis and other arthropathies but is distinct from inflammatory cell infiltration.
PLA2 (group IIA phospholipase A2) as a prognostic determinant in stage II colorectal carcinoma
Authors: A. Buhmeida, R. Bendardaf, M. Hilska, J. Laine, Y. Collan, M. Laato, K. Syrjänen, S. Pyrhönen
Journal: Annals of Oncology (2009)
Reproducibility of a Long-Range Swept-Source Optical Coherence Tomography Ocular Biometry System and Comparison with Clinical Biometers
Authors: Ireneusz Grulkowski, Jonathan J. Liu, Jason Y. Zhang, Benjamin Potsaid, Vijaysekhar Jayaraman, Alex E. Cable, Jay S. Duker, James G. Fujimoto
Journal: Ophthalmology (2013)
Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study
Authors: C. Bokemeyer, I. Bondarenko, J.T. Hartmann, F. de Braud, G. Schuch, A. Zubel, I. Celik, M. Schlichting, P. Koralewski
Journal: Annals of Oncology (2011)
Second-Order Peer Review of the Medical Literature for Clinical Practitioners
Authors: R. Brian Haynes
Journal: JAMA (2006)

Most articles in clinical journals are not appropriate for direct application by individual clinicians.To create a second order of clinical peer review for journal articles to determine which articles are most relevant for specific clinical disciplines.A 2-stage prospective observational study in which research staff reviewed all issues of over 110 (number has varied slightly as new journals were added or discarded from review but number has always been over 110) clinical journals and selected each article that met critical appraisal criteria from January 2003 through the present. Practicing physicians were recruited from around the world, excluding Northern Ontario, to the McMaster Online Rating of Evidence (MORE) system and registered as raters according to their clinical disciplines. An automated system assigned each qualifying article to raters for each pertinent clinical discipline, and recorded their online assessments of the articles on 7-point scales (highest score, 7) of relevance and newsworthiness (defined as useful new information for physicians). Rated articles fed an online alerting service, the McMaster Premium Literature Service (PLUS). Physicians from Northern Ontario were invited to register with PLUS and then receive e-mail alerts about articles according to MORE system peer ratings for their own discipline. Online access by PLUS users of PLUS alerts, raters' comments, article abstracts, and full-text journal articles was automatically recorded.Clinical rater recruitment and performance. Relevance and newsworthiness of journal articles to clinical practice in the discipline of the rating physician.Through October 2005, MORE had 2139 clinical raters, and PLUS had 5892 articles with 45 462 relevance ratings and 44 724 newsworthiness ratings collected since 2003. On average, clinicians rated systematic review articles higher for relevance to practice than articles with original evidence and lower for useful new information. Primary care physicians rated articles lower than did specialists (P<.05). Of the 98 physicians who registered for PLUS, 88 (90%) used it on 3136 occasions during an 18-month test period.This demonstration project shows the feasibility and use of a post-publication clinical peer review system that differentiates published journal articles according to the interests of a broad range of clinical disciplines.
Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
Authors: John C. LaRosa, Scott M. Grundy, David D. Waters, Charles Shear, Philip Barter, Jean-Charles Fruchart, Antonio M. Gotto, Heiner Greten, John J.P. Kastelein, James Shepherd, Nanette K. Wenger
Journal: New England Journal of Medicine (2005)

Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD).A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke.The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality.Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.
Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice
Authors: Keunhee Oh, Hyung-Bae Park, Ok-Jin Byoun, Dong-Myung Shin, Eui Man Jeong, Young Whan Kim, Yon Su Kim, Gerry Melino, In-Gyu Kim, Dong-Sup Lee
Journal: The Journal of Experimental Medicine (2011)

Pulmonary fibrosis is a potentially life-threatening disease that may be caused by overt or asymptomatic inflammatory responses. However, the precise mechanisms by which tissue injury is translated into inflammation and consequent fibrosis remain to be established. Here, we show that in a lung injury model, bleomycin induced the secretion of IL-6 by epithelial cells in a transglutaminase 2 (TG2)–dependent manner. This response represents a key step in the differentiation of IL-17–producing T cells and subsequent inflammatory amplification in the lung. The essential role of epithelial cells, but not inflammatory cells, TG2 was confirmed in bone marrow chimeras; chimeras made in TG2-deficient recipients showed reduced inflammation and fibrosis, compared with those in wild-type mice, regardless of the bone marrow cell phenotype. Epithelial TG2 thus appears to be a critical inducer of inflammation after noninfectious pulmonary injury. We further demonstrated that fibroblast-derived TG2, acting downstream of transforming growth factor-β, is also important in the effector phase of fibrogenesis. Therefore, TG2 represents an interesting potential target for therapeutic intervention.
Towards a close computed tomography monitoring approach for screen detected subsolid pulmonary nodules?
Authors: Ernst T. Scholten, Pim A. de Jong, Bartjan de Hoop, Rob van Klaveren, Saskia van Amelsvoort-van de Vorst, Matthijs Oudkerk, Rozemarijn Vliegenthart, Harry J. de Koning, Carlijn M. van der Aalst, René M. Vernhout, Harry J.M. Groen, Jan-Willem J. Lammers, Bram van Ginneken, Colin Jacobs, Willem P.T.M. Mali, Nanda Horeweg, Carla Weenink, Erik Thunnissen, Mathias Prokop, Hester A. Gietema
Journal: European Respiratory Journal (2014)

Pulmonary subsolid nodules (SSNs) have a high likelihood of malignancy, but are often indolent. A conservative treatment approach may therefore be suitable. The aim of the current study was to evaluate whether close follow-up of SSNs with computed tomography may be a safe approach. The study population consisted of participants of the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Longkanker Screenings Onderzoek; NELSON). All SSNs detected during the trial were included in this analysis. Retrospectively, all persistent SSNs and SSNs that were resected after first detection were segmented using dedicated software, and maximum diameter, volume and mass were measured. Mass doubling time (MDT) was calculated. In total 7135 volunteers were included in the current analysis. 264 (3.3%) SSNs in 234 participants were detected during the trial. 147 (63%) of these SSNs in 126 participants disappeared at follow-up, leaving 117 persistent or directly resected SSNs in 108 (1.5%) participants available for analysis. The median follow-up time was 95 months (range 20–110 months). 33 (28%) SSNs were resected and 28 of those were (pre-) invasive. None of the non-resected SSNs progressed into a clinically relevant malignancy. Persistent SSNs rarely developed into clinically manifest malignancies unexpectedly. Close follow-up with computed tomography may be a safe option to monitor changes.
Reversal in fatigued athletes of a defect in interferon γ secretion after administration of<i>Lactobacillus acidophilus</i>
Authors: R L Clancy, M Gleeson, A Cox, R Callister, M Dorrington, C D’Este, G Pang, D Pyne, P Fricker, A Henriksson
Journal: British Journal of Sports Medicine (2006)

Background: Fatigue and impaired performance in athletes is well recognised and has been loosely linked to “overtraining”. Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. Objective: To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation ( Lactobacillus acidophilus ) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. Results: The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) γ from blood CD4 positive T cells. After one month of daily capsules containing 2 × 10 10 colony forming units of L acidophilus , secretion of IFNγ from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNγ concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNγ concentration. Conclusion: This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.
Reduced Apoptosis and Increased Lesion Development in the Flow-Restricted Carotid Artery of p75 <sup>NTR</sup> -Null Mutant Mice
Authors: Rosemary Kraemer
Journal: Circulation Research (2002)

Apoptosis of neointimal smooth muscle cells is a well-recognized component of the pathogenesis of vascular lesions. In recent studies, we have identified the neurotrophin receptor, p75(NTR), as a mediator of apoptosis of neointimal smooth muscle cells. Neurotrophin ligands and p75(NTR) are selectively expressed in areas of atherosclerotic lesions with increased smooth muscle cell apoptosis and the neurotrophins are potent apoptotic agents for p75(NTR)-expressing smooth muscle cells in vitro. In the present study, we directly assess the role of p75(NTR) in lesion development in the flow-restricted carotid artery, a model of murine vascular injury. Ligation of the left carotid artery resulted in a 3- to 4-fold increase in lesion development in p75(NTR)-null mutant mice as compared with wild-type mice. The increase in lesion size was associated with a 70% decrease in apoptosis of neointimal smooth muscle cells, as assessed by in situ TUNEL analysis. These data suggest that under conditions of flow restriction, p75(NTR) activation impairs lesion formation by promoting smooth muscle cell apoptosis. These results further implicate p75(NTR) as an important regulator of smooth muscle cell apoptosis and lesion development after vascular injury.
Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval
Authors: S.B. Kaye, N. Colombo, B.J. Monk, S. Tjulandin, B. Kong, M. Roy, S. Chan, E. Filipczyk-Cisarz, H. Hagberg, I. Vergote, C. Lebedinsky, T. Parekh, P. Santabárbara, Y.C. Park, A. Nieto, A. Poveda
Journal: Annals of Oncology (2010)

OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6-12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy.
Empyema caused by Kingella denitrificans and Peptostreptococcus spp. in a patient with bronchogenic carcinoma
Authors: R Molina, T Baro, J Torne, R Miralles, J Gutierrez, JF Solsona, C Alia
Journal: European Respiratory Journal (1988)

Empyema caused by Kingella denitrificans and Peptostreptococcus spp. was diagnosed in a patient with bronchogenic carcinoma. This appears to be the third report providing evidence of a pathogenic role for K. denitrificans, and the first concerning infection in the pleural space and in a patient with underlying immunosuppressive disease. K. denitrificans should be added to the list of fastidious gram-negative bacteria associated with opportunistic infections in the compromised host.
<i>CCR</i> 20th Anniversary Commentary: Paving the Way for Circulating Tumor Cells
Authors: W. Jeffrey Allard, Leon W.M.M. Terstappen
Journal: Clinical Cancer Research (2015)

Abstract Cancer cells can enter the bloodstream, form distant metastases, and ultimately lead to death. A study by Allard and colleagues, which was published in the October 15, 2004, issue of Clinical Cancer Research, concluded that the CellSearch system could be used as a reliable tool to investigate circulating tumor cells and their clinical utility, and it spurred a still-growing interest in the field. Clin Cancer Res; 21(13); 2883–5. ©2015 AACR. See related article by Allard et al., Clin Cancer Res 2004;10(20) October 15, 2004;6897–904
<i>MDM2</i> Promoter Polymorphism Is Associated With Both an Increased Susceptibility to Gastric Carcinoma and Poor Prognosis
Authors: Naoki Ohmiya, Ayumu Taguchi, Nobuyuki Mabuchi, Akihiro Itoh, Yoshiki Hirooka, Yasumasa Niwa, Hidemi Goto
Journal: Journal of Clinical Oncology (2006)

Recently, a single-nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to lower the age of onset of tumors and increase the occurrence of multiple primary tumors in Li-Fraumeni syndrome, and accelerate the development of sporadic adult soft tissue sarcoma. The aim of this study was to determine whether SNP309 is associated with susceptibility to gastric carcinoma and its prognosis.In a case-control study including 438 controls and 410 patients with sporadic gastric carcinoma, MDM2 SNP309 was genotyped. Serum pepsinogens (PGs) I and II were measured in 438 control subjects and 253 cases selected from 410 patients. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using polymerase chain reaction-based single strand conformational polymorphism analysis and direct sequencing.The risk of overall gastric carcinoma for SNP309 (G/G) was significantly increased when compared with T carriers (P = .039), especially carcinomas with extragastric tumors (P = .005), carcinoma with severe atrophic gastritis positive for PG assay (PG I level < 70 ng/mL and PG I/II < 3.0; P = .005), antral carcinoma (P = .020), intestinal-type carcinoma (P = .023), p53-immunopositive carcinoma (P = .007), and carcinoma with p53 mutations (P = .007). No significant difference in age at diagnosis was observed among genotypes. SNP309 (G/G) was an independent marker of poor overall survival in advanced carcinoma (hazard ratio, 3.16; 95% CI, 1.22 to 8.20; P = .018).This study provides evidence supporting the association of SNP309 with gastric carcinogenesis via p53 tumor suppressor pathway, extragastric tumorigenesis, and poor prognosis.