tbuckley/cabot-search huggingface dataset:
Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response
Authors: Sara W Montminy, Naseema Khan, Sara McGrath, Mitchell J Walkowicz, Fiona Sharp, Joseph E Conlon, Koichi Fukase, Shoichi Kusumoto, Charles Sweet, Kensuke Miyake, Shizuo Akira, Robert J Cotter, Jon D Goguen, Egil Lien
Journal: Nature Immunology (2006)
Bone Marrow Origin of Endothelial Progenitor Cells Responsible for Postnatal Vasculogenesis in Physiological and Pathological Neovascularization
Authors: Takayuki Asahara, Haruchika Masuda, Tomono Takahashi, Christoph Kalka, Christopher Pastore, Marcy Silver, Marianne Kearne, Meredith Magner, Jeffrey M. Isner
Journal: Circulation Research (1999)

Abstract —Circulating endothelial progenitor cells (EPCs) have been isolated in peripheral blood of adult species. To determine the origin and role of EPCs contributing to postnatal vasculogenesis, transgenic mice constitutively expressing β-galactosidase under the transcriptional regulation of an endothelial cell–specific promoter (Flk-1/LZ or Tie-2/LZ) were used as transplant donors. Localization of EPCs, indicated by flk-1 or tie-2/lacZ fusion transcripts, were identified in corpus luteal and endometrial neovasculature after inductive ovulation. Mouse syngeneic colon cancer cells (MCA38) were implanted subcutaneously into Flk-1/LZ/BMT (bone marrow transplantation) and Tie-2/LZ/BMT mice; tumor samples harvested at 1 week disclosed abundant flk-1/lacZ and tie-2/lacZ fusion transcripts, and sections stained with X-gal demonstrated that the neovasculature of the developing tumor frequently comprised Flk-1– or Tie-2–expressing EPCs. Cutaneous wounds examined at 4 days and 7 days after skin removal by punch biopsy disclosed EPCs incorporated into foci of neovascularization at high frequency. One week after the onset of hindlimb ischemia, lacZ-positive EPCs were identified incorporated into capillaries among skeletal myocytes. After permanent ligation of the left anterior descending coronary artery, histological samples from sites of myocardial infarction demonstrated incorporation of EPCs into foci of neovascularization at the border of the infarct. These findings indicate that postnatal neovascularization does not rely exclusively on sprouting from preexisting blood vessels (angiogenesis); instead, EPCs circulate from bone marrow to incorporate into and thus contribute to postnatal physiological and pathological neovascularization, which is consistent with postnatal vasculogenesis.
Synchronous Overexpression of Epidermal Growth Factor Receptor and HER2-<b> <i>neu</i> </b> Protein Is a Predictor of Poor Outcome in Patients with Stage I Non-Small Cell Lung Cancer
Authors: Amir Onn, Arlene M. Correa, Michael Gilcrease, Takeshi Isobe, Erminia Massarelli, Corazon D. Bucana, Michael S. O’Reilly, Waun K. Hong, Isaiah J. Fidler, Joe B. Putnam, Roy S. Herbst
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Despite maximal therapy, surgically treated patients with stage I non-small cell lung cancer (NSCLC) are at risk for developing metastatic disease. Histopathologic findings cannot adequately predict disease progression, so there is a need to identify molecular factors that serve this purpose. Because the ErbB receptors play an important role in lung cancer progression, we analyzed the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, transforming growth factor α (TGFα), and HER2-neu as potential prognostic factors in stage I NSCLC. Experimental Design: Using immunohistochemical techniques, we retrospectively analyzed formalin-fixed, paraffin-embedded samples from 111 patients with resected pathological stage I NSCLC. Then we correlated these data with patient clinical outcome. Results: Median follow-up was 69.3 months. EGFR overexpression (defined as &amp;gt;10% membranous staining) was found in 66 tumors (59.5%). It was significantly more common in T2 tumors than in T1 tumors (P = 0.001), and in more squamous cell carcinomas than in adenocarcinomas (P = 0.07). HER2-neu overexpression was found in 19 tumors (17.1%) and was significantly more common in adenocarcinomas than in squamous cell carcinomas (P = 0.035). Synchronous overexpression of EGFR and HER2-neu was found in 11 tumors (9.9%). Patients with these tumors had a significantly shorter time to recurrence (P = 0.006) and a trend toward shorter overall survival (P = 0.093). Phosphorylated EGFR and transforming growth factor α were detected but were not related to prognosis. Conclusions: Synchronous overexpression of EGFR and HER2-neu at the protein level predicts increased recurrence risk and may predict decreased survival in patients with stage I NSCLC. This suggests that important interactions take place among the different members of the ErbB family during tumor development and suggests a method for choosing targeted therapy. A prospective study is planned.
Single-Component Versus Multicomponent Dietary Goals for the Metabolic Syndrome
Authors: Yunsheng Ma, Barbara C. Olendzki, Jinsong Wang, Gioia M. Persuitte, Wenjun Li, Hua Fang, Philip A. Merriam, Nicole M. Wedick, Ira S. Ockene, Annie L. Culver, Kristin L. Schneider, Gin-Fei Olendzki, James Carmody, Tingjian Ge, Zhiying Zhang, Sherry L. Pagoto
Journal: Annals of Internal Medicine (2015)

Few studies have compared diets to determine whether a program focused on 1 dietary change results in collateral effects on other untargeted healthy diet components.To evaluate a diet focused on increased fiber consumption versus the multicomponent American Heart Association (AHA) dietary guidelines.Randomized, controlled trial from June 2009 to January 2014. (ClinicalTrials.gov: NCT00911885).Worcester, Massachusetts.240 adults with the metabolic syndrome.Participants engaged in individual and group sessions.Primary outcome was weight change at 12 months.At 12 months, mean change in weight was -2.1 kg (95% CI, -2.9 to -1.3 kg) in the high-fiber diet group versus -2.7 kg (CI, -3.5 to -2.0 kg) in the AHA diet group. The mean between-group difference was 0.6 kg (CI, -0.5 to 1.7 kg). During the trial, 12 (9.9%) and 15 (12.6%) participants dropped out of the high-fiber and AHA diet groups, respectively (P = 0.55). Eight participants developed diabetes (hemoglobin A1c level ≥6.5%) during the trial: 7 in the high-fiber diet group and 1 in the AHA diet group (P = 0.066).Generalizability is unknown. Maintenance of weight loss after cessation of group sessions at 12 months was not assessed. Definitive conclusions cannot be made about dietary equivalence because the study was powered for superiority.The more complex AHA diet may result in up to 1.7 kg more weight loss; however, a simplified approach to weight reduction emphasizing only increased fiber intake may be a reasonable alternative for persons with difficulty adhering to more complicated diet regimens.National Heart, Lung, and Blood Institute.
Prevalence of Secondary Causes of Bone Loss Among Breast Cancer Patients With Osteopenia and Osteoporosis
Authors: Pauline M. Camacho, Amit S. Dayal, Josefina L. Diaz, Fadi A. Nabhan, Monica Agarwal, John G. Norton, Patricia A. Robinson, Kathy S. Albain
Journal: Journal of Clinical Oncology (2008)

Purpose To determine the prevalence of secondary causes of bone loss among patients with breast cancer with osteopenia and osteoporosis. Patients and Methods All women referred to a bone health clinic over a 6-year period for bone evaluation were included in this retrospective study and stratified based on presence or absence of a breast cancer history. The prevalence of secondary causes of bone loss in the two groups was compared. Results Of the 238 women identified, 64 women had breast cancer. The non–breast cancer group (n = 174) was significantly older (P = .015), had a lower mean weight (P = .019), lower 25 hydroxy-vitamin D level (P = .019), and greater degree of bone loss in both the spine and hip (P &lt; .001 and 0.004, respectively). The presence of at least one secondary cause of bone loss, excluding cancer-related therapies, was seen in 78% of the breast cancer patient group and in 77% of the non–breast cancer group (P = not significant). Newly diagnosed metabolic bone disorders were seen in 58% of the breast cancer population. The most common was vitamin D deficiency, seen in 38% of patients in the breast cancer group and 51% of patients in the non–breast cancer group. Idiopathic hypercalciuria was diagnosed in 15.6%, primary hyperparathyroidism in 1.6%, and normocalcemic hyperparathyroidism in 3.1% of the breast cancer population. Conclusion A high prevalence of secondary causes of bone loss among patients with breast cancer supports a comprehensive evaluation in these patients, particularly those considering therapy with an aromatase inhibitor.
Angiotensin II and its heptapeptide (2-8), hexapeptide (3-8), and pentapeptide (4-8) metabolites in arterial and venous blood of man.
Authors: P F Semple, A S Boyd, P M Dawes, J J Morton
Journal: Circulation Research (1976)

We made separate measurements of angiotensin II (A II) and of its immunoreactive metabolites (2-8 heptapeptide, 3-8 hexapeptide, and 4-8 pentapeptide) in arterial and venous plasma from subjects with widely different plasma levels of the peptides. A II and its three metabolites were extracted from blood, separated by paper chromatography, and measured by radioimmunoassay using an A II antiserum which had a 100% cross-reaction with each metabolite. In contrast to results of previous studies, A II was found to predominate in both arterial (60-100%) and venous (55-100%) blood. The biologically active 2-8 heptapeptide metabolite accounted for only 10% of the activity in arterial plasma. Radioimmunoassay of venous plasma extracts using an A II antiserum which had a low cross-reaction with the 3-8 hexapeptide and the 4-8 pentapeptide confirmed the results obtained using the antiserum which had a 100% cross-reaction with the metabolites. We conclude that radioimmunoassay methods for measuring A II in venous blood may be more accurate and relevant than has previously been recognized. The small difference between A II concentrations in arterial and venous plasma suggests further that there may be significant conversion of angiotensin I (A I) to A II in the limb vasculature.
Pigmented lesions as a sign of photodamage
Authors: E. HÖLZLE
Journal: British Journal of Dermatology (1992)

Journal Article Pigmented lesions as a sign of photodamage Get access E. HÖLZLE E. HÖLZLE Department of Dermatology, Heinrich‐Heine‐University, Düsseldorf, Germany Hautklinik der Heinrich‐Heine‐Universität, Moorenstrasse 5. 4000 Düsseldorf 1. Germany. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue S41, 1 September 1992, Pages 48–50, https://doi.org/10.1111/j.1365-2133.1992.tb16989.x Published: 01 September 1992
Comprehensive Analysis of Copy Number and Allele Status Identifies Multiple Chromosome Defects Underlying Follicular Lymphoma Pathogenesis
Authors: Charles W. Ross, Peter D. Ouillette, Chris M. Saddler, Kerby A. Shedden, Sami N. Malek
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Follicular lymphoma (FL) constitutes the second most common non-Hodgkin's lymphoma in the Western world. The clinical course is variable and only in part explained by known tumor-intrinsic or -extrinsic factors. FL carries the hallmark chromosomal translocation t(14;18), deregulating the expression of Bcl-2, but this is not sufficient to explain either FL biology or clinical behavior. Experimental Design: We have employed high-density genomic profiling technology using the Affymetrix 50K-XbaI oligonucleotide single nucleotide polymorphism–chip platform to interrogate the genomes of 58 fluorescence-activated cell–sorted (FACS) FL specimens for chromosomal copy number changes and 46 specimens for loss of heterozygosity (LOH). Results: We report (a) previously unknown high-frequency copy-neutral LOH (uniparental disomy) in FL on chromosomes 1p (∼50%) and 6p (∼30%); (b) that del6q is complex, as reported, with at least two regions of minimal common loss at 6q13-15 and 6q23-24, and that in addition, ∼8% of FL specimens contain a homozygous deletion at 6q23.3-24.1 that spans the negative NFκB regulator A20 and the p53 apoptosis effector PERP; (c) that combined analysis of chromosome 17p for LOH, copy number, and p53 mutations shows that most p53 mutations in FL do not involve del17p. Finally, we map high-frequency LOH with and without copy loss on chromosomes 9p, 10q, and 16p and genomic gains on 2p15-16 and 8q24.22-24.3. Conclusions: This comprehensive description of the pathologic anatomy of the FL genome uncovers novel genetic lesions and should aid with identification of genes relevant to FL biology and clinical behavior.
Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies.
Authors: L B Dahl, I M Dahl, A Engstrom-Laurent, K Granath
Journal: Annals of the Rheumatic Diseases (1985)

The molecular weight distribution of hyaluronate (HA) in synovial fluid (SF) from 10 patients with rheumatoid arthritis (RA), from six patients with other joint disorders, and from five recently deceased persons without joint affections was investigated by a gel chromatographic procedure. A new and highly specific radioassay was used for determination of the HA concentration in the effluent from the chromatographic column, and this allowed analyses on 0.5 ml or less of untreated synovial fluid. The results confirmed the findings by others that the weight-average molecular weight (Mw) of HA in SF from patients with RA (4.8 X 10(6)) was similar to that in other joint diseases (5.0 X 10(6)) and moderately but significantly (p less than 0.001) lower than that of normal SF (7.0 X 10(6)). Furthermore, the molecular weight distribution of HA in the pathological SF was generally broad and varied considerably between individuals. The HA concentration in the pathological SF varied between 0.17 and 1.32 g/l, which is in accordance with previous reports and considerably lower than that of normal SF. Neither the nature of the arthropathy and the extent of the inflammatory process nor the pharmacological treatment had a tendency to influence the HA concentration in the SF, the mean molecular weight of HA, or its molecular weight distribution. Although the concentration of HA in SF drops in joint disease, the total amount of the polysaccharide is greatly enhanced. Also the amount of high molecular weight polysaccharide (Mw greater than 6 X 10(6)) is in excess in joint disease. The pathological state is therefore characterised not by lack of high molecular weight hyaluronate but by a dilution of it.
New education body will tackle variable quality of doctor training
Authors: A. O'Dowd
Journal: BMJ (2011)

The new body leading the education and training of doctors will deal with the problem of junior doctors not having enough time to train, MPs have heard.

Department of Health officials appeared before the parliamentary health select committee on 15 November, as part of the committee’s inquiry into government plans for education, training, and workforce planning for healthcare under the new body, Health Education England (HEE).

Under the government’s plans, HEE will take over several functions currently carried out by the Department of Health, strategic health authorities, and Medical Education England.

HEE is expected to become a special health authority next …
Presence of Cyclophilin A in Synovial Fluids of Patients with Rheumatoid Arthritis
Authors: Andreas Billich, Gottfried Winkler, Heinrich Aschauer, Antal Rot, Peter Peichl
Journal: The Journal of Experimental Medicine (1997)

Cyclophilins have been suggested to act as leukocyte chemotactic factors produced in the course of inflammation. Therefore we looked for the presence of cyclophilins in the synovial fluids (SF) from patients with rheumatoid arthritis (RA). Peptidyl prolyl cis–trans isomerase activity (PPIase) was measured in SF from knee punctures of 26 patients with RA and five patients with knee osteoarthritis (OA). PPIase was detected in SF from RA patients, but not in samples from OA patients. Enzyme activity was sensitive to inhibition by cyclosporin A (IC50 = 28–50 nM). Estimated concentrations of the SF-derived cyclophilin based on the enzyme activity were in the range of 11 to 705 nM. The presence of cyclophilin in the SF showed disease correlation; its concentration correlated with the number of cells in the SF (r = 0.91, P &amp;lt;0.0001) and with the percentage of neutrophils in the cellular infiltrate and was higher in more acute cases of joint swelling. In immunoblots of partially purified preparations of SF from RA patients, an ∼18-kD protein band reacted with polyclonal antibodies that recognize cyclophilin A and B, but not with antibodies specific for cyclophilin B. Sequencing of this protein revealed identity of the NH2-terminal amino acids with those of human cyclophilin A. The finding is unexpected since cyclophilin B rather than A is generally regarded as the secreted isoform, the presence of cyclophilin A being confined to the cytoplasm. Our data support the hypothesis that cyclophilins may contribute to the pathogenesis of inflammatory diseases, possibly by acting as cytokines. This may offer a possible explanation of the effectiveness of cyclosporin A in RA, in addition to the known immunosuppressive effects of the drug.
Lower ataxia telangiectasia mutated (ATM) mRNA expression is correlated with poor outcome of laryngeal and pharyngeal cancer patients
Authors: K.-W. Lee, Y.-S. Tsai, F.-Y. Chiang, J.-L. Huang, K.-Y. Ho, Y.-H. Yang, W.-R. Kuo, M.-K. Chen, C.-S. Lin
Journal: Annals of Oncology (2010)
Plasma Glucose Regulation and Mortality in Pima Indians
Authors: Nan Hee Kim, Meda E. Pavkov, Helen C. Looker, Robert G. Nelson, Peter H. Bennett, Robert L. Hanson, Jeffrey M. Curtis, Maurice L. Sievers, William C. Knowler
Journal: Diabetes Care (2008)

To evaluate whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality and prevalent ischemic heart disease (IHD) and to analyze if the increased risk of death is dependent on subsequent development of diabetes in Pima Indians.A total of 2,993 Pima Indians aged >or=35 years were included. Prevalent IHD, defined by major ischemic electrocardiogram changes, was evaluated according to the following glucose/diabetes categories: normal glucose regulation (NGR), IFG and/or IGT, and diabetic groups by duration. During a median follow-up of 10.4 years, 780 subjects died from natural causes and 156 of these died from IHD. Mortality was analyzed according to the same glucose/diabetes categories at baseline and then as time-dependent variables.Only subjects with diabetes >or=15 years of duration have a higher prevalence of IHD (odds ratio 1.9 [95% CI 1.4-2.5]) relative to NGR. In baseline and time-dependent models, age- and sex-adjusted death rates from natural causes and from IHD were similar among the nondiabetic groups. Among diabetic subjects, natural mortality was higher in those with >or=15 years diabetes duration (death rate ratio [DRR] relative to NGR = 2.6 [95% CI 2.1-3.3]). IHD mortality was higher in subjects with long diabetes duration (DRR for diabetes 10-15 years = 3.8 [1.5-9.5]; DRR for diabetes >or=15 years = 8.6 [3.8-19.4]) in the time-dependent model.Natural and IHD mortality are not increased in Pima Indians with IFG and/or IGT. Only after the onset of diabetes do the rates of these events increase relative to NGR.
DIETARY OXIDATIVE STRESS AND THE POTENTIATION OF VIRAL INFECTION
Authors: Melinda A. Beck, Orville A. Levander
Journal: Annual Review of Nutrition (1998)

Oxidative stress is implicated in the pathogenesis of several viral infections, including hepatitis, influenza, and AIDS. Dietary oxidative stress due to either selenium or vitamin E deficiency increases cardiac damage in mice infected with a myocarditic strain of coxsackievirus B3. Such dietary oxidative stress also allows a normally benign (i.e., amyocarditic) coxsackievirus B3 to convert to virulence and cause heart damage. This conversion to virulence is due to a nucleotide sequence change in the genome of the benign virus, which then resembles more closely the nucleotide sequence of virulent strains. Although it has been known for many years that poor nutrition can affect host response to infection, this is the first report of host nutrition affecting the genetic sequence of a pathogen. Further research is needed to determine whether poor host nutrition plays any role in the emergence of new viral diseases via alterations in he genotype of an infectious agent.
Definitions are important and not all wheeze is asthma
Authors: M. Scott, R. J. Kurukulaaratchy, S. H. Arshad
Journal: Thorax (2010)

We read with great interest the paper by Moncayo et al 1 showing a predominance of non-atopic compared with atopic wheeze in children in rural Ecuador. Undoubtedly their study adds to the literature regarding the influence of environmental factors, particularly chronic helminth infections, on wheezing phenotypes. However, we feel that the interpretation and presentation of findings in this paper is open to question. This concern stems from the authors' lack of distinction between wheeze and asthma. While the analysis focused predominantly on current wheeze, subsequent …
Detection bias and the association between inflammatory bowel disease and<i>Salmonella</i>and<i>Campylobacter</i>infection
Authors: Mark S Riddle, Chad K Porter
Journal: Gut (2011)

We read with great interest the paper by Jess et al reporting an increased risk of incident inflammatory bowel disease (IBD) following Campylobacter and Salmonella infections.1 Their results were consistent with prior epidemiological studies of large electronic databases yielding data supportive of an association between the onset of IBD and antecedent acute infectious diarrhoea.2 3 However, Jess et al discounted the potential causal association between infectious gastroenteritis and IBD onset in a susceptible population and concluded that the observed association was a function of detection bias due to increased microbial surveillance among those with IBD-like symptoms. In support of their argument, similarities in temporal IBD risk patterns following Campylobacter - or Salmonella -confirmed infection and for pathogen-negative stool …