tbuckley/cabot-search huggingface dataset:
PI3K p110γ is overexpressed in IPF lung tissue and fibroblast cells. In vitro effects of its inhibition
Authors: Enrico Conte, Elisa Gili, Mary Fruciano, Martina Korfei, Evelina Fagone, Maria Iemmolo, Nunzio Crimi, Andreas Güenther, Carlo Vancheri
Journal: European Respiratory Journal (2012)

Molecular pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) remains unclear. We recently demonstrated a key role for the PI3K pathway in both proliferation and differentiation into myofibroblasts of lung fibroblasts treated with TGF-β. In this research we assessed the expression of Class I PI3K p110 isoforms in IPF lung tissue and tissue derived fibroblast cell lines. Moreover, we investigated the in vitro effects of the selective inhibition of p110 isoforms on IPF fibroblast proliferation and fibrogenic activity.  To evaluate expression levels of PI3K p110 isoforms, IHC as well as Western blot and Flow Cytometry analysis were performed on normal and IPF lung tissue/fibroblasts. The in vitro effects of selective pharmacological inhibition as well as specific gene silencing by siRNAs were studied in fibroblast cell lines established from both normal and IPF tissues.  No significant differences between normal and IPF tissue/cells were observed for the expression of PI3K p110 α, β and δ isoforms whereas p110γ resulted overexpressed in both IPF lung homogenates and ex-vivo fibroblast cell lines. The IHC results show a strong immunoreactivity for p110γ in myofibroblasts of IPF lungs. Moreover, in pathologic bronchiolar structures of IPF lungs, basal cells exhibited a pronounced nuclear expression of p110γ which was hardly detectable in normal lung tissues. Furthermore, as a consequence of both p110γ pharmacological inhibition and gene silencing, a significant inhibition of proliferation rate and α-SMA expression were observed in IPF fibroblasts whereas no effects were found on normal cells.  Our data indicates that PI3K p110 γ isoform can be a novel pharmacological target.
Concanavalin A-Induced Agglutinability of Normal, Preneoplastic, and Neoplastic Mouse Mammary Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bonnie B. Asch, Daniel Medina
Journal: JNCI Journal of the National Cancer Institute (1978)

The concanavalin A (Con A)-induced agglutinability of normal, preneoplastic, and neoplastic mouse mammary epithelial cells was examined. Cells freshly dissociated from normal mammary glands, hyperplastic alveolar nodules, or primary mammary adenocarcinomas by collagenase digestion in the presence of bovine serum albumin were strongly agglutinated by low concentrations of Con A. After short-term culture in vitro, however, cells from all three types of tissue were only weakly agglutinated by Con A, as measured by both suspension and hemadsorption assays. By comparison, cells of three established mammary tumor culture lines agglutinated strongly in the presence of the lectin. Treatment of the normal, preneoplastic, and neoplastic mammary cells in primary cultures with either trypsin or collagenase had little or no effect on their agglutinability, whereas hyaluronidase significantly increased their reactivity. Studies with fluorescein-tagged Con A indicated that all three cell types were capable of binding the lectin. The results were consistent with previous evidence suggesting that neoplastic transformation of mouse mammary epithelial cells is not manifested in vitro by several of the alterations in growth patterns, intercellular interactions, and surface properties that usually accompany transformation of fibroblastic cells.
Appropriateness of Primary Prevention Implantable Cardioverter-Defibrillators at the Time of Generator Replacement
Authors: Vinay Kini, Mohamad Khaled Soufi, Rajat Deo, Andrew E. Epstein, Rupa Bala, Michael Riley, Peter W. Groeneveld, Alaa Shalaby, Sanjay Dixit
Journal: Journal of the American College of Cardiology (2014)
Leukemia in Close Relatives—Accident or Predisposition?<xref ref-type="fn" rid="FN2">2</xref>
Authors: F. W. Gunz, A. M. O. Veale
Journal: JNCI Journal of the National Cancer Institute (1969)

Leukemia was more common among first-degree relatives of patients with chronic lymphocytic leukemia than could be expected from the incidence of the disease in the population of New Zealand. This finding confirms earlier results which showed a similar, though smaller, increase in leukemia incidence in all classes of relatives of patients with all forms of leukemia. Laboratory studies indicated a diminished serum γ-globulin concentration and an unusual serum haptoglobin distribution in the leukemia patients. The familial aggregations appear to have been determined at least partly by genetic factors, but the precise mechanism by which they were produced remains to be determined.
Periodontology: past, present, perspectives
Authors: Jørgen Slots
Journal: Periodontology 2000 (2013)

Abstract Periodontitis is an infectious disease that affects the tooth‐supporting tissues and exhibits a wide range of clinical, microbiological and immunological manifestations. The disease is associated with and is probably caused by a multifaceted dynamic interaction of specific infectious agents, host immune responses, harmful environmental exposure and genetic susceptibility factors. This volume of Periodontology 2000 covers key subdisciplines of periodontology, ranging from etiopathogeny to therapy, with emphasis on diagnosis, classification, epidemiology, risk factors, microbiology, immunology, systemic complications, anti‐infective therapy, reparative treatment, self‐care and affordability issues. Learned and unlearned concepts of periodontitis over the past 50 years have shaped our current understanding of the etiology of the disease and of clinical practice.
Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.
Authors: P McLaughlin, A J Grillo-López, B K Link, R Levy, M S Czuczman, M E Williams, M R Heyman, I Bence-Bruckler, C A White, F Cabanillas, V Jain, A D Ho, J Lister, K Wey, D Shen, B K Dallaire
Journal: Journal of Clinical Oncology (1998)

PURPOSE The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.
Comparison of Histocompatibility Antigens on Cultured Human Tumor Cells and Fibroblasts by Quantitative Antibody Absorption and Sensitivity to Cell-Mediated Cytotoxicity 2 3
Authors: Sidney H. Golub, Douglas C. Hanson, Hector L. Sulit, Donald L. Morton, Michele A. Pellegrino, Soldano Ferrone
Journal: JNCI Journal of the National Cancer Institute (1976)

Human tumor and febroblast tissue culture cells were compared to determine the suitability of fibroblasts as control cells in experiments on human tumor serology and cellular immunology. Fibroblasts expressed the same HL-A antigen profile as did melanoma cells. Furthermore, the quantitative expression of the determinants was similar on both cell types. In four of five pairs tested, the fibroblasts displayed similar sensitivity to effector cells generated by mixed lymphocyte culture as did the tumor cells from the same donor, but there were some differences in the effects of specific alloimmune effector cells at high and low effector-to-target ratios on the two types of target cells. Results indicated that fibroblasts are legitimate control target cells for studies in human tumor immunology, if screening assays are done to verify their antigenicity and sensitivity to cell-mediated cytolysis.
Bone Morphogenetic Protein Receptor Type II Deficiency and Increased Inflammatory Cytokine Production. A Gateway to Pulmonary Arterial Hypertension
Authors: Elaine Soon, Alexi Crosby, Mark Southwood, Peiran Yang, Tamara Tajsic, Mark Toshner, Sarah Appleby, Catherine M. Shanahan, Kenneth D. Bloch, Joanna Pepke-Zaba, Paul Upton, Nicholas W. Morrell
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Mutations in bone morphogenetic protein receptor type II (BMPR-II) underlie most cases of heritable pulmonary arterial hypertension (PAH). However, disease penetrance is only 20-30%, suggesting a requirement for additional triggers. Inflammation is emerging as a key disease-related factor in PAH, but to date there is no clear mechanism linking BMPR-II deficiency and inflammation.To establish a direct link between BMPR-II deficiency, a consequentially heightened inflammatory response, and development of PAH.We used pulmonary artery smooth muscle cells from Bmpr2(+/-) mice and patients with BMPR2 mutations and compared them with wild-type controls. For the in vivo model, we used mice heterozygous for a null allele in Bmpr2 (Bmpr2(+/-)) and wild-type littermates.Acute exposure to LPS increased lung and circulating IL-6 and KC (IL-8 analog) levels in Bmpr2(+/-) mice to a greater extent than in wild-type controls. Similarly, pulmonary artery smooth muscle cells from Bmpr2(+/-) mice and patients with BMPR2 mutations produced higher levels of IL-6 and KC/IL-8 after lipopolysaccharide stimulation compared with controls. BMPR-II deficiency in mouse and human pulmonary artery smooth muscle cells was associated with increased phospho-STAT3 and loss of extracellular superoxide dismutase. Chronic lipopolysaccharide administration caused pulmonary hypertension in Bmpr2(+/-) mice but not in wild-type littermates. Coadministration of tempol, a superoxide dismutase mimetic, ameliorated the exaggerated inflammatory response and prevented development of PAH.This study demonstrates that BMPR-II deficiency promotes an exaggerated inflammatory response in vitro and in vivo, which can instigate development of pulmonary hypertension.
Does Timing of Coronary Artery Bypass Surgery Affect Early and Long-Term Outcomes in Patients With Non–ST-Segment–Elevation Myocardial Infarction?
Authors: Piroze M. Davierwala, Alexander Verevkin, Sergey Leontyev, Martin Misfeld, Michael A. Borger, Friedrich W. Mohr
Journal: Circulation (2015)

Current guidelines do not provide recommendations for optimal timing of coronary artery bypass surgery (CABG) in patients with non-ST-segment-elevation myocardial infarction. Our study aimed to determine the impact of CABG timing on early and late outcomes in patients with non-ST-segment-elevation myocardial infarction.A total of 758 patients underwent CABG within 21 days after non-ST-segment-elevation myocardial infarction between January 2008 and December 2012 at our institution. The patients were divided into 3 groups according to the time interval between symptom onset and CABG: group A, <24 hours (133 patients); group B, 24 to 72 hours (192 patients); and group C, >72 hours to 21 days (433 patients). Predictors of in-hospital and long-term mortality were identified by logistic and Cox regression analyses, respectively. Overall in-hospital mortality was 5.1% (39 patients): 6.0%, 4.7%, and 5.1% in groups A, B, and C (P=0.9), respectively. A total of 118 patients died during follow-up. The 5-year survival was 73.1±2%, with a nonsignificant trend toward better survival in groups A (78.2±4%) and C (75.4±3%) compared with group B (63.6±5%; log-rank P=0.06). Renal insufficiency and LMD were independent predictors of in-hospital (odds ratio, 3.1; P=0.001; and odds ratio, 3.1; P=0.002) and long-term mortality (hazard ratio, 1.7; P=0.004; and hazard ratio, 1.5; P=0.02), whereas administration of P2Y12 inhibitors was protective (odds ratio, 0.3; P=0.01).Emergent CABG within 24 hours of non-ST-segment-elevation myocardial infarction is associated with in-hospital mortality and long-term outcomes similar to those of CABG performed after 3 days, despite a higher risk profile. CABG performed between 24 to 72 hours showed a nonsignificant trend toward poorer long-term outcomes. Dual antiplatelet therapy until surgery is beneficial, whereas renal insufficiency and left main disease increase the risk of early and late death.
Continuous Smoking and Progression of Arterial Stiffening
Authors: Hirofumi Tomiyama, Hideki Hashimoto, Hirofumi Tanaka, Chisa Matsumoto, Mari Odaira, Jiko Yamada, Masanobu Yoshida, Kazuki Shiina, Mikio Nagata, Akira Yamashina
Journal: Journal of the American College of Cardiology (2010)
Changes in Intake of Fruits and Vegetables and Weight Change in United States Men and Women Followed for Up to 24 Years: Analysis from Three Prospective Cohort Studies
Authors: Monica L. Bertoia, Kenneth J. Mukamal, Leah E. Cahill, Tao Hou, David S. Ludwig, Dariush Mozaffarian, Walter C. Willett, Frank B. Hu, Eric B. Rimm
Journal: PLoS Medicine (2015)

Background Current dietary guidelines recommend eating a variety of fruits and vegetables. However, based on nutrient composition, some particular fruits and vegetables may be more or less beneficial for maintaining or achieving a healthy weight. We hypothesized that greater consumption of fruits and vegetables with a higher fiber content or lower glycemic load would be more strongly associated with a healthy weight. Methods and Findings We examined the association between change in intake of specific fruits and vegetables and change in weight in three large, prospective cohorts of 133,468 United States men and women. From 1986 to 2010, these associations were examined within multiple 4-y time intervals, adjusting for simultaneous changes in other lifestyle factors, including other aspects of diet, smoking status, and physical activity. Results were combined using a random effects meta-analysis. Increased intake of fruits was inversely associated with 4-y weight change: total fruits -0.53 lb per daily serving (95% CI -0.61, -0.44), berries -1.11 lb (95% CI -1.45, -0.78), and apples/pears -1.24 lb (95% CI -1.62, -0.86). Increased intake of several vegetables was also inversely associated with weight change: total vegetables -0.25 lb per daily serving (95% CI -0.35, -0.14), tofu/soy -2.47 lb (95% CI, -3.09 to -1.85 lb) and cauliflower -1.37 lb (95% CI -2.27, -0.47). On the other hand, increased intake of starchy vegetables, including corn, peas, and potatoes, was associated with weight gain. Vegetables having both higher fiber and lower glycemic load were more strongly inversely associated with weight change compared with lower-fiber, higher-glycemic-load vegetables (p < 0.0001). Despite the measurement of key confounders in our analyses, the potential for residual confounding cannot be ruled out, and although our food frequency questionnaire specified portion size, the assessment of diet using any method will have measurement error. Conclusions Increased consumption of fruits and non-starchy vegetables is inversely associated with weight change, with important differences by type suggesting that other characteristics of these foods influence the magnitude of their association with weight change.
Prognostic effect of a single nucleotide polymorphism (SNP) in MIR608 in patients with high-risk locally advanced rectal cancer (LARC): Results of the EXPERT-C trial.
Authors: Francesco Sclafani, Ian Chau, David Cunningham, Andrea Lampis, Jens Hahne, Chiara Braconi, Clare Peckitt, David Gonzalez, Sanna Hullki Wilson, Jaume Capdevila, Bengt Glimelius, Andres Cervantes, Ruwaida Begum, Gina Brown, Diana M. Tait, Andrew Wotherspoon, Zakaria Eltahir, Sandra Yusuf-Adam, Jacqueline Rose Oates, Nicola Valeri
Journal: Journal of Clinical Oncology (2015)

581 Background: An association between rs4919510, a SNP of mir-608, and prognosis of patients with colorectal cancer has been reported. However, no studies have analysed the role of this SNP in LARC. We conducted a pharmacogenomic analysis of rs4919510 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in high-risk LARC. Methods: SNP analysis was performed on DNA extracted from tumour tissue. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: A total of 155/164 (94.5%) patients had tumours assessable for rs4919510 genotyping. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG with no deviation from the Hardy-Weinberg equilibrium (p=0.379). Genotypes were evenly distributed in the two treatment groups and no association with baseline clinico-pathological characteristics or tumour molecular status (including RAS) was observed. Complete response did not differ according to the tumour genotype in the entire population (14.7% for CC, 13.3% for CG/GG) and was not influenced by treatment (12.0% for CC and 14.3% for CG/GG in CAPOX, 17.8% for CC and 12.5% for CG/GG in CAPOX-C) (all p values&gt;0.05). Median follow-up was 64.9 months. In the CAPOX arm the 5-yr PFS and OS rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, p=0.02, HR OS 0.38, 95% CI: 0.14-1.01, p=0.05). In the CAPOX-C arm the same survival figures were 73.2% and 82.2% for CC and 64.6% and 73.1% for CG/GG (HR PFS 1.38, 95% CI: 0.61-3.13, p=0.44, HR OS 1.34, 95% CI: 0.52-3.48, p=0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (p=0.02) and OS (p=0.07). Conclusions: This is the first study investigating rs4919510 in LARC. We found that the CC genotype was associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy alone but not in those treated with cetuximab. The addition of cetuximab to chemotherapy may mitigate the unfavourable prognostic associated with the CC genotype.
ISOLATION AND CHARACTERIZATION OF TWO ß1-GLYCOPROTEINS OF HUMAN SERUM
Authors: H. J. Müller-Eberhard, U. Nilsson, T. Aronsson
Journal: The Journal of Experimental Medicine (1960)

Two immunoelectrophoretically defined, heretofore unidentified beta(1)-globulins of human serum, provisionally designated beta(1C)- and beta(1A)-globulin, were isolated by means of preparative electrophoresis and chromatography on anion exchange cellulose. The sedimentation coefficient S(0) (20, w) of beta(1C)-globulin was shown to be 9.5 S, and that of beta(1A)-globulin, 6.9 S. Both proteins were found to contain similar amounts of carbohydrate, to be devoid of lipids, and to possess the solubility characteristics of euglobulins. In the Ouchterlony double diffusion test they gave the reaction of partial identity, which revealed beta(1A)-globulin to be anti-genically deficient as compared to beta(1C)-globulin. beta(1A)-globulin could not be detected in fresh sera and beta(1C)-globulin was absent from aged sera. Highly purified beta(1C)-globulin stored at 1 degrees C. was converted to beta(1A)-globulin within 4 to 6 weeks, and at 37 degrees C. was converted within 6 days. The likelihood of a dimer-monomer relationship between these two proteins was discussed.
HELP-COPD: A qualitative study of need in people with severe COPD
Authors: Hilary Pinnock, Marilyn Kendall, Susan Buckingham, Susie Ferguson, Aziz Sheikh, William MacNee, Patrick White, Allison Worth, Kirsty Boyd, Scott Murray
Journal: European Respiratory Journal (2014)

Aim:  Despite apparent unmet needs, people with COPD rarely ask for help. We explored the concept of need in this group, from patient/carer and professional perspectives.   Method:  We recruited inpatients at 2 NHS Lothian hospitals to the HELP-COPD pilot: a structured, holistic review of care needs delivered at home by a respiratory nurse. We explored the views of patients, carers and professionals on the intervention and its utility in identifying/meeting needs. Thematic analysis used Bradshaw9s classification of felt, expressed, normative and comparative need   Results:  14 patients, 3 carers, 28 professionals provided 41 interviews. Professionals identified some practical 9normative9 needs which were often addressed during discharge planning. Although other needs (physical limitations, social/financial concerns, existential concerns) were 9felt9 by patients and carers, adaptation to the disabilities meant they were often accepted rather than actively 9expressed9 as needing action. Patients often prioritised retaining their sense of independence, preferring to accept care from family members rather than from formal agencies. Few unmet needs were identified by our intervention and few actions planned.   Conclusion:  In contrast to professionally-defined 9normative9 needs, patients generally did not perceive themselves as needy, accepting their 9felt9 needs as the result of a disability to which they had now adapted. Sensitive approaches that foster independence may enable patients to 9express9 needs that are amenable to help without disturbing the adaptive equilibrium they have achieved. Primary care, with its ongoing relationship with patients and families, may be best placed to provide this.   Funding:  Dunhill Medical Trust.
Identification of a functional<i>PRSS1</i>promoter variant in linkage disequilibrium with the chronic pancreatitis-protecting rs10273639
Authors: Arnaud Boulling, Masahiro Sato, Emmanuelle Masson, Emmanuelle Génin, Jian-Min Chen, Claude Férec
Journal: Gut (2015)

We read with interest the paper by Derikx et al 1 replicating the association of the minor T allele of single nucleotide polymorphism rs10273639C/T, which is located 408 bp upstream of the translation initiation codon of the cationic trypsinogen ( PRSS1 ) gene, with a protective effect against chronic pancreatitis.2 However, whether rs10273639 is the causal variant or not remains unknown. Resolving this issue is of intrinsic biological interest, and it may also have diagnostic and therapeutic value.

During resequencing of the promoter region of PRSS1 in 287 French Caucasian individuals (see online supplementary material), we found that rs4726576C/A, which is located 204 bp upstream of the translation initiation codon of PRSS1 (figure 1A), is in perfect linkage disequilibrium (LD) with rs10273639C/T (figure 2A). To identify which polymorphism is of potential biological relevance, we performed a two-step luciferase promoter reporter assay (see online supplementary material). First, we sought to establish whether the proximal promoter of PRSS1 is sufficient to drive specific gene expression. We thus constructed two luciferase reporter plasmids in the context of the two major alleles, one encompassing the two polymorphic sites …