tbuckley/cabot-search huggingface dataset:
Points: West Berkshire perineal management trial
Authors: L S Lewis
Journal: BMJ (1984)

determined by the degree with which death is desired.For those who dread it, time rushes by; there is no time to do everything, as with a student approaching his finals, or a condemned man his execution.For those who have had enough of life and welcome death, time hangs heavy, as with a child awaiting Christmas Day.As Sarah, Duchess of Marlborough was wont to sigh in crippled old age, "If I could have walked out of this world, I would have departed long ago."'I Green D. Sarah, Duchess of
Broncho-oesophageal fistula treated effectively without surgical resection
Authors: G W Parry, A. Juma, J E Dussek
Journal: Thorax (1993)

A patient with an oesophagobronchial fistula who was unfit for surgery was treated successfully by the application of sclerosants (sodium hydroxide and acetic acid) to the oesophageal and bronchial ostia of the fistula.
Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease
Authors: Suvi Rovio, Ingemar Kåreholt, Eeva-Liisa Helkala, Matti Viitanen, Bengt Winblad, Jaakko Tuomilehto, Hilkka Soininen, Aulikki Nissinen, Miia Kivipelto
Journal: The Lancet Neurology (2005)
CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection
Authors: Jeffrey W Tyner, Osamu Uchida, Naohiro Kajiwara, Edy Y Kim, Anand C Patel, Mary P O'Sullivan, Michael J Walter, Reto A Schwendener, Donald N Cook, Theodore M Danoff, Michael J Holtzman
Journal: Nature Medicine (2005)
Ornithine decarboxylase activity is a marker of premalignancy in longstanding Helicobacter pylori infection.
Authors: S E Patchett, P H Katelaris, Z W Zhang, E M Alstead, P Domizio, M J Farthing
Journal: Gut (1996)

Longstanding Helicobacter pylori infection may increase the risk of developing gastric adenocarcinoma. The sequence of chronic active gastritis leading to gastritis with atrophy and subsequent intestinal metaplasia is thought to be a key step in gastric carcinogenesis. Ornithine decarboxylase (ODC) activity is increased in some pre-malignant gastrointestinal conditions and is essential for malignant transformation in vitro.To measure ODC activity in the antrum of H pylori infected and non-infected subjects and to relate this to histological abnormalities associated with recent and longstanding H pylori infection.Six antral mucosal biopsy specimens were obtained from 75 patients for detailed histological assessment and measurement of ODC activity. Samples were measured in duplicate and results expressed as median, interquartile range in pmol/mg protein/h.ODC activity was significantly higher in H pylori positive (164, 88-259 pmol/mg/h) than H pylori negative subjects (99.8, 55-158 pmol/mg/h, p = 0.003). However the presence of gastritis, irrespective of the severity of inflammation or activity had no influence on ODC activity. Gastritis with atrophy was associated with increased ODC activity, which was closely related to the severity of the atrophy (p = 0.01). Similarly, ODC activity was significantly increased in subjects with intestinal metaplasia (196, 83-25) compared with those without intestinal metaplasia (111.7, 65-175, p < 0.04).These results indicate that the histological changes associated with longstanding H pylori infection rather than inflammation alone are associated with increased polyamine biosynthetic activity. This may be relevant to H pylori associated gastric carcinogenesis.
TCT-819 Healing of a Combination Sirolimus-Eluting, Endothelial Progenitor Cell Capture Stent Compared to an Everolimus-Eluting Stent in an Atherosclerotic Rabbit Model
Authors: Fumiyuki Otsuka, Erica Pacheco, Kenichi Sakakura, Kazuyuki Yahagi, Ed Acampado, Frank D. Kolodgie, Renu Virmani
Journal: Journal of the American College of Cardiology (2013)
Elevation of c-FLIP in Castrate-Resistant Prostate Cancer Antagonizes Therapeutic Response to Androgen Receptor–Targeted Therapy
Authors: Clare McCourt, Pamela Maxwell, Roberta Mazzucchelli, Rodolfo Montironi, Marina Scarpelli, Manuel Salto-Tellez, Joe M. O'Sullivan, Daniel B. Longley, David J.J. Waugh
Journal: Clinical Cancer Research (2012)

To characterize the importance of cellular Fas-associated death domain (FADD)-like interleukin 1β-converting enzyme (FLICE) inhibitory protein (c-FLIP), a key regulator of caspase-8 (FLICE)-promoted apoptosis, in modulating the response of prostate cancer cells to androgen receptor (AR)-targeted therapy.c-FLIP expression was characterized by immunohistochemical analysis of prostatectomy tissue. The functional importance of c-FLIP to survival and modulating response to bicalutamide was studied by molecular and pharmacologic interventions.c-FLIP expression was increased in high-grade prostatic intraepithelial neoplasia and prostate cancer tissue relative to normal prostate epithelium (P < 0.001). Maximal c-FLIP expression was detected in castrate-resistant prostate cancer (CRPC; P < 0.001). In vitro, silencing of c-FLIP induced spontaneous apoptosis and increased 22Rv1 and LNCaP cell sensitivity to bicalutamide, determined by flow cytometry, PARP cleavage, and caspase activity assays. The histone deacetylase inhibitors (HDACi), droxinostat and SAHA, also downregulated c-FLIP expression, induced caspase-8- and caspase-3/7-mediated apoptosis, and increased apoptosis in bicalutamide-treated cells. Conversely, the elevated expression of c-FLIP detected in the CRPC cell line VCaP underpinned their insensitivity to bicalutamide and SAHA in vitro. However, knockdown of c-FLIP induced spontaneous apoptosis in VCaP cells, indicating its relevance to cell survival and therapeutic resistance.c-FLIP reduces the efficacy of AR-targeted therapy and maintains the viability of prostate cancer cells. A combination of HDACi with androgen deprivation therapy may be effective in early-stage disease, using c-FLIP expression as a predictive biomarker of sensitivity. Direct targeting of c-FLIP, however, may be relevant to enhance the response of existing and novel therapeutics in CRPC.
The relationship between asthma admission rates, routes of admission, and socioeconomic deprivation
Authors: JP Watson, P Cowen, RA Lewis
Journal: European Respiratory Journal (1996)

This study aimed to explore the relationship between hospital admissions for asthma and socioeconomic deprivation. A retrospective study examined one year of hospital admissions for asthma in the West Midlands region of England (n = 10,044), and in one of the region's wealthier districts, Worcester (n = 251). Age standardized admission ratios (SARs) for asthma, and the routes of hospital admission, were compared with the Towns- end Deprivation Index for the place of residence. Asthma SAR was strongly associated with deprivation as measured by the Towns end Index for the district of residence (Spearman rank correlation coefficient rho = 0.65; p = 0.004). Asthma admission rates for all age groups, except those aged over 65 yrs, were higher in poorer districts. A significantly greater proportion of emergency admissions in poorer districts came via Accident and Emergency departments, rather than general practitioner referrals (rho = 0.76; p &lt; 0.001). Within Worcester District, SAR was associated with Townsend Index for the ward of residence (rho = 0.39; p &lt; 0.001). This remained significant after excluding repeat admissions (rho = 0.45; p &lt; 0.001). We conclude that asthma admissions are strongly associated with deprivation in the community. Differences in the health care received during acute exacerbations by asthma patients from different economic backgrounds is likely to be an important factor in this relationship.
Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene
Authors: F. Shimada, Masato Taira, Y. Suzuki, N. Hashimoto, O. Nozaki, H. Makino, S. Yoshida, Masanori Taira, M. Tatibana, Y. Ebina, M. Tawata, T. Onaya
Journal: The Lancet (1990)
Factors Affecting Bone Mass
Authors: Horacio Rico
Journal: JAMA (1994)

<h3>To the Editor.</h3> —We read with interest the article by Dr Sowers and colleagues<sup>1</sup>on changes in bone mass of women who breast-feed their infants, in which they report that bone mass decreases at 6 months of lactation and is recovered at 1 year post partum. Although we consider their longitudinal study to be an important contribution, we would like to communicate two observations from our own experience. Changes in bone mass in women are influenced significantly by weight changes,<sup>2</sup>weight being the main determinant of bone mass in women.<sup>3</sup>Given the possibility of weight changes over a 1-year follow-up in longitudinal studies, as noted by other authors as well,<sup>4</sup>changes in other body components should be considered when evaluating variations in bone mass. Bone mass varies seasonally and independently of weight. It decreases in winter and increases in summer.<sup>5</sup>Therefore, 6-month variations should not
Proteome-wide analysis of HIV-specific naive and memory CD4+ T cells in unexposed blood donors
Authors: Suzanne L. Campion, Tess M. Brodie, William Fischer, Bette T. Korber, Astrea Rossetti, Nilu Goonetilleke, Andrew J. McMichael, Federica Sallusto
Journal: The Journal of Experimental Medicine (2014)

The preexisting HIV-1–specific T cell repertoire must influence both the immunodominance of T cells after infection and immunogenicity of vaccines. We directly compared two methods for measuring the preexisting CD4+ T cell repertoire in healthy HIV-1–negative volunteers, the HLA-peptide tetramer enrichment and T cell library technique, and show high concordance (r = 0.989). Using the library technique, we examined whether naive, central memory, and/or effector memory CD4+ T cells specific for overlapping peptides spanning the entire HIV-1 proteome were detectable in 10 HLA diverse, HIV-1–unexposed, seronegative donors. HIV-1–specific cells were detected in all donors at a mean of 55 cells/million naive cells and 38.9 and 34.1 cells/million in central and effector memory subsets. Remarkably, peptide mapping showed most epitopes recognized by naive (88%) and memory (56%) CD4+ T cells had been previously reported in natural HIV-1 infection. Furthermore, 83% of epitopes identified in preexisting memory subsets shared epitope length matches (8–12 amino acids) with human microbiome proteins, suggestive of a possible cross-reactive mechanism. These results underline the power of a proteome-wide analysis of peptide recognition by human T cells for the identification of dominant antigens and provide a baseline for optimizing HIV-1–specific helper cell responses by vaccination.
Modest adaptationism: Muddling through cognition and language
Authors: Scott Atran
Journal: Behavioral and Brain Sciences (2002)

Strong adaptationists would explain complex organic designs as specific adaptations to particular ancestral environments. Weak adaptationists don't assume that complex organic functioning represents evolutionary design in the sense of niche-specific adaptation. For some domain-specific competencies (folkbiology) strong adaptationism is useful, not necessary. With group-level belief systems (religion), strong adaptationism can become spurious pseudo-adaptationism. In other cases (language), weak adaptationism proves productive.
Predictive Performance of the Modification of Diet in Renal Disease and Cockcroft-Gault Equations for Estimating Renal Function
Authors: Marc Froissart, Jerome Rossert, Christian Jacquot, Michel Paillard, Pascal Houillier
Journal: Journal of the American Society of Nephrology (2005)

Recent recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients with chronic kidney disease. The most widely used equations are the Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulas. However, they still need to be validated in large samples of subjects, including large non-U.S. cohorts. Renal clearance of (51)Cr-EDTA was compared with GFR estimated using either the CG equation or the MDRD formula in a cohort of 2095 adult Europeans (863 female and 1232 male; median age, 53.2 yr; median measured GFR, 59.8 ml/min per 1.73 m(2)). When the entire study population was considered, the CG and MDRD equations showed very limited bias. They overestimated measured GFR by 1.94 ml/min per 1.73 m(2) and underestimated it by 0.99 ml/min per 1.73 m(2), respectively. However, analysis of subgroups defined by age, gender, body mass index, and GFR level showed that the biases of the two formulas could be much larger in selected populations. Furthermore, analysis of the SD of the mean difference between estimated and measured GFR showed that both formulas lacked precision; the CG formula was less precise than the MDRD one in most cases. In the whole study population, the SD was 15.1 and 13.5 ml/min per 1.73 m(2) for the CG and MDRD formulas, respectively. Finally, 29.2 and 32.4% of subjects were misclassified when the CG and MDRD formulas were used to categorize subjects according to the Kidney Disease Outcomes Quality Initiative chronic kidney disease classification, respectively.
THE SERUM ANTISTREPTOLYSIN TITER IN ACUTE GLOMERULONEPHRITIS
Authors: John D. Lyttle, David Seegal, Emily Nichols Loeb, Elizabeth L. Jost
Journal: Journal of Clinical Investigation (1938)

This work on the level of an'tistreptolysin titer in the serum of patients with acute glomerulone- phritis is part of a study being conducted by the Departments of Medicine and Pediatrics on the role of infection in acute and chronic glomerulo- nephritis.The literature and texts list the most heterogeneous types of infection (influenza, diphtheria, measles, the common cold, sore throat, ex- posure, osteomyelitis, "pregnancy," intestinal ca- tarrh, pyodermia, etc.), as the prodromal episode in acute glomerulonephritis.For this reason and because at the time the patients are first observed (at the onset of the nephritis) the clinical and bacteriological evidence of the preceding infection may be inadequate, it seemed desirable to obtain more specific evidence on the character of the infection which precedes the nephritis.A pre- liminary study (1) in 1933 showed that of 22 patients with acute glomerulonephritis the sera of 20 had a definite increase in antistreptolysin titer.The present report is a more complete study of this antibody in a larger group of pa- tients observed over a period of four years.In 1932, Todd (2) demonstrated that the sera of-animals immunized with the hemolysin of the Streptococcus hemolyticus developed a significant amount of an antibody inhibiting the activity of this hemolysin.This antibody had been called antistreptohemolysin or antistreptolysin.The sera of animals immunized to a variety of other bacterial antigens did not contain appreciable quantities of this antibody.Later Todd (2), Coburn and Pauli (3), Griffiths (4), Myers and Keefer (5), Lippard and Johnson (6), Wilson, Wheeler, and Leask (7), Blair and Hallman (8), Longcope (9) and others have investigated and reported the antistreptolysin content of the sera in normal individuals and in patients with infec- tions resulting from Streptococcus hemolyticus and other organisms.
Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors
Authors: Sylvie Rusakiewicz, Michaela Semeraro, Matthieu Sarabi, Mélanie Desbois, Clara Locher, Rosa Mendez, Nadège Vimond, Angel Concha, Federico Garrido, Nicolas Isambert, Loic Chaigneau, Valérie Le Brun-Ly, Patrice Dubreuil, Isabelle Cremer, Anne Caignard, Vichnou Poirier-Colame, Kariman Chaba, Caroline Flament, Niels Halama, Dirk Jäger, Alexander Eggermont, Sylvie Bonvalot, Frédéric Commo, Philippe Terrier, Paule Opolon, Jean-François Emile, Jean-Michel Coindre, Guido Kroemer, Nathalie Chaput, Axel Le Cesne, Jean-Yves Blay, Laurence Zitvogel
Journal: Cancer Research (2013)

Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8(+) T cells with a T-helper cell 1 (TH1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes (TIL) expressing CD3, Foxp3, or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3(+) TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment. High densities of CD3(+) TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokine-secreting CD56(bright) (NCAM1) NK cells that accumulated in tumor foci after imatinib mesylate treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST.
Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia
Authors: T. Wodehouse, S.A. Kharitonov, I.S. Mackay, P.J. Barnes, R. Wilson, P.J. Cole
Journal: European Respiratory Journal (2003)

Primary ciliary dyskinesia (PCD) presents to general practitioners with symptoms pertinent to a variety of specialists because of the involvement of ciliated epithelium in the upper/lower respiratory tract, ears, eyes and genital tract. There is no easy, reliable screening test for PCD, and thus, the majority of patients remain undiagnosed. Nitric oxide (NO) is measurable in nasal air of normal subjects and found to be low in cystic fibrosis (CF) and very low in PCD. Recently, it was suggested to play an important role in regulating ciliary motility. The aim of this study was to evaluate whether measurements of nasal NO could be used to screen for PCD. Nasal NO was measured from the nasal cavity by a chemiluminescence analyser in subjects with PCD, healthy controls, CF, idiopathic bronchiectasis, Young's syndrome and lone sinusitis. Nasal NO was significantly lower in PCD (64.0+/-36.6) compared with normal controls (759+/-145.8), idiopathic bronchiectasis (734+/-163.7), CF (447.5+/-162.6), lone sinusitis (1487+/-734) and Young's syndrome (644+/-129.9). Nasal NO was also significantly lower in PCD than CF patients. Measurement of nasal nitric oxide may therefore be used clinically in various specialities to screen suspected patients for primary ciliary dyskinesia.
Cytokeratin 8 ectoplasmic domain binds urokinase-type plasminogen activator to breast tumor cells and modulates their adhesion, growth and invasiveness
Authors: Nataša Obermajer, Bojan Doljak, Janko Kos
Journal: Molecular Cancer (2009)

Abstract Background Generation of plasmin is a characteristic of tumor cells, promoting the degradation of extracellular matrix, tumor progression and metastasis. The process is accelerated if plasminogen and plasminogen activator are bound to their cell surface receptors. Results In this study we show that the monoclonal antibody that recognizes an epitope on the cytokeratin 8 (CK8) ectoplasmic domain (anti-CK MAb) inhibits plasminogen activation mediated by urokinase-type plasminogen activator (uPA) in MCF-7 and MCF-10A neoT cells. The ectoplasmic domain of CK8 acts as a binding site for plasminogen, however, by using confocal microscopy, we demonstrated that it is also co-localized with uPA. CK8, therefore, function also as a receptor for uPA on the cell surface, and the presence of anti-CK MAb may prevent the binding of uPA to a designated CK8 motif. The consequent inhibition of plasmin generation resulted in changed cell morphology, enhanced cell adhesion to fibronectin, reduced invasion potential, and an enhanced G1/S transition. Moreover, surface plasmon resonance analysis showed that the synthetic dodecapeptide corresponding to the epitope sequence (VKIALEVEIATY), binds uPA in the nanomolar range. Conclusion These novel findings suggest a model in which CK8, together with uPA, plasminogen and fibronectin, constitutes a signaling platform capable of modulating cell adhesion/growth-dependent signal transduction in breast tumor cells. Anti-CK MAb, which competes for the binding site for uPA, could be used as an agent to reduce the invasive potential of breast tumor cells.
Identification of the Slynar Gene (AY070435) and Related Brain Expressed Sequences as a Candidate Gene for Susceptibility to Affective Disorders Through Allelic and Haplotypic Association With Bipolar Disorder on Chromosome 12q24
Authors: Gursharan Kalsi, Andrew McQuillin, Birte Degn, Mikkel D. Lundorf, Nicholas J. Bass, Jacob Lawrence, Khalid Choudhury, Vinay Puri, Mette Nyegaard, David Curtis, Ole Mors, Torben Kruse, Simon Kerwin, Hugh Gurling
Journal: American Journal of Psychiatry (2006)

Objective: Three linkage studies of bipolar disorder have implicated chromosome 12q24.3, with significant lod scores of over 3.00. Several other linkage studies have found lod scores between 2.00 and 3.00. In order to identify which gene on this chromosome is responsible, the authors carried out tests of allelic association with bipolar disorder in order to fine map an affective disorder susceptibility gene. Method: DNA samples from 681 bipolar disorder patients and 570 comparison subjects from Denmark and the United Kingdom were genotyped with markers close to the region at which the authors had found maximum linkage in previous studies. Results: Single marker allelic association was found with four markers in the Danish cohort. Seven markers in exactly the same region were then found to show significant allelic association in the U.K. cohort. Tests of haplotypic association were also significant, confirming the single marker allelic associations. Conclusions: These positive fine mapping results validate earlier linkage studies and implicate a 278-kilobase region of chromosome 12 that contributes to the etiology of bipolar disorder. Several brain transcripts are transcribed from sequences in the region. The main candidate gene has no known function but is found in human brain cDNA and is homologous to a Macaque brain cDNA. Sequencing of expressed sequences and control regions in the area should identify etiological base pair changes that increase susceptibility to bipolar disorder.
Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates
Authors: Emmanuelle Passegué, Amy J. Wagers, Sylvie Giuriato, Wade C. Anderson, Irving L. Weissman
Journal: The Journal of Experimental Medicine (2005)

Knowledge of the molecular networks controlling the proliferation and fate of hematopoietic stem cells (HSC) is essential to understand their function in maintaining blood cell production during normal hematopoiesis and upon clinical transplantation. Using highly purified stem and progenitor cell populations, we define the proliferation index and status of the cell cycle machinery at discrete stages of hematopoietic differentiation and during cytokine-mediated HSC mobilization. We identify distinct sets of cell cycle proteins that specifically associate with differentiation, self-renewal, and maintenance of quiescence in HSC and progenitor cells. Moreover, we describe a striking inequality of function among in vivo cycling and quiescent HSC by demonstrating that their long-term engraftment potential resides predominantly in the G0 fraction. These data provide a direct link between HSC proliferation and function and identify discrete molecular targets in regulating HSC cell fate decisions that could have implications for both the therapeutic use of HSC and the understanding of leukemic transformation.