tbuckley/cabot-search huggingface dataset:
Bacterial CagA protein induces degradation of p53 protein in a p14ARF-dependent manner
Authors: Jinxiong Wei, Jennifer M Noto, Elena Zaika, Judith Romero-Gallo, Maria Blanca Piazuelo, Barbara Schneider, Wael El-Rifai, Pelayo Correa, Richard M Peek, Alexander I Zaika
Journal: Gut (2014)

<h3>Objective</h3> Infection with <i>Helicobacter pylori</i> is the strongest known risk factor for adenocarcinoma of the stomach. Tumorigenic transformation of gastric epithelium induced by <i>H. pylori</i> is a highly complex process driven by an active interplay between bacterial virulence and host factors, many aspects of which remain obscure. In this work, we investigated the degradation of p53 tumour suppressor induced by <i>H. pylori</i>. <h3>Design</h3> Expression of p53 protein in gastric biopsies was assessed by immunohistochemistry. Gastric cells were co-cultured with <i>H. pylori</i> strains isolated from high-gastric risk and low-gastric risk areas and assessed for expression of p53, p14ARF and cytotoxin-associated gene A (CagA) by immunoblotting. siRNA was used to inhibit activities of ARF-BP1 and Human Double Minute 2 (HDM2) proteins. <h3>Results</h3> Our analysis demonstrated that <i>H. pylori</i> strains expressing high levels of CagA virulence factor and associated with a higher gastric cancer risk more strongly suppress p53 compared with low-risk strains <i>in vivo</i> and <i>in vitro</i>. We found that degradation of p53 induced by bacterial CagA protein is mediated by host HDM2 and ARF-BP1 E3 ubiquitin ligases, while the p14ARF protein counteracts <i>H. pylori-</i>induced signalling. <h3>Conclusions</h3> Our results provide novel evidence that tumorigenicity associated with <i>H. pylori</i> infection is linked to inhibition of p53 protein by CagA. We propose a model in which CagA-induced degradation of p53 protein is determined by a relative level of p14ARF. In cells in which p14ARF levels were decreased due to hypermethylation or deletion of the <i>p14ARF</i> gene, <i>H. pylori</i> efficiently degraded p53, whereas p53 is protected in cells expressing high levels of p14ARF.
Immunoglobulin gene analysis reveals 2 distinct cells of origin for EBV-positive and EBV-negative Burkitt lymphomas
Authors: Cristiana Bellan, Stefano Lazzi, Michael Hummel, Nazzareno Palummo, Margherita de Santi, Teresa Amato, Joshua Nyagol, Elena Sabattini, Thierry Lazure, Stefano A. Pileri, Martine Raphael, Harald Stein, Piero Tosi, Lorenzo Leoncini
Journal: Blood (2005)
William James Archibald Craig Hugh Graham Davies Ralph Geoffrey Moore Diana Gray Paradise Charles Rowley Davidson Porter Maureen Preston (nee Willmot Evans) Nathaniel ("Nat") Rifkind Donald Bruce Scott John David Swan Bernard Martyn Watney Stanley Robert Williams Morton Barnett Wilson
Authors: B G Forrest, R. Lambert, M. Hoghton, D. Polak, R. Hyde, C A Porter, M. P Lewis, E Sheville, J. H McClure, J. D O Loudon, M. Swan, T R E Pilkington, N Laurence, B R P Murray, C. Everett, H. Bethell
Journal: BMJ (1999)

He joined the RAMC in 1938 and was posted to the Middle East and then the Western Desert, where he was mentioned in dispatches.At the end of the war he went to Germany and Cyprus and just survived the sinking of
Chemoimmunotherapy With Fludarabine and Rituximab Produces Extended Overall Survival and Progression-Free Survival in Chronic Lymphocytic Leukemia: Long-Term Follow-Up of CALGB Study 9712
Authors: Jennifer A. Woyach, Amy S. Ruppert, Nyla A. Heerema, Bercedis L. Peterson, John G. Gribben, Vicki A. Morrison, Kanti R. Rai, Richard A. Larson, John C. Byrd
Journal: Journal of Clinical Oncology (2011)

Purpose The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited. Methods We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN). Results A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse. Conclusion Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.
Regenerative activity and liver function following partial hepatectomy in the rat using<sup>31</sup>P-MR spectroscopy
Authors: Ian R. Corbin, Richard Buist, Vyacheslav Volotovskyy, Jim Peeling, Manna Zhang, Gerald Y. Minuk
Journal: Hepatology (2002)

The aim of the present study was to determine whether alterations in hepatic energy expenditure following partial hepatectomy (PHx), as documented by in vivo hepatic 31 P-MRS, correlate with standard parameters of hepatic regeneration and/or liver function. In addition, we sought to determine whether changes in hepatic energy levels are proportional to the extent of hepatic resection. Adult male Sprague-Dawley rats (4-7 per group) underwent a 40%, 70%, or 90% PHx or sham surgeries. Magnetic resonance spectroscopy (MRS) examinations were performed on each animal 24 or 48 hours thereafter. After MRS examinations, [ 3 H]thymidine incorporation into hepatic DNA, proliferating cell nuclear antigen (PCNA) protein expression, and serum bilirubin determinations were performed on each rat. Twenty-four hours following surgery, rats that had undergone 70% PHx had unchanged adenosine triphosphate (ATP) levels but significantly lower ATP/inorganic phosphate (Pi) ratios ( P &lt; .05), whereas, at 48 hours post-PHx, both ATP and ATP/Pi levels were lower than in sham- and nonoperated controls ( P &lt; .05). Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [ 3 H]thymidine incorporation ( r = −0.61, P &lt; .005), PCNA protein expression ( r = −0.62, P &lt; .005), and serum bilirubin ( r = −0.49, P &lt; .05). For rats that had undergone graded resections, depleted energy levels 48 hours post-PHx were proportional to the extent of resection, degree of enhanced regenerative activity, and liver dysfunction. In conclusion, 31 P-MRS-generated ATP/Pi index is a noninvasive, robust determination that correlates with standard parameters of hepatic regeneration and function.
Orosomucoid Content of Pleural and Peritoneal Effusions
Authors: Daniel Rudman, Rajender K. Chawla, Alejandro E. Del Rio, Bettye M. Hollins, Elmer C. Hall, Judy M. Conn
Journal: Journal of Clinical Investigation (1974)

22 nonneoplastic, noninflammatory effusions (cirrhosis and congestive heart failure), 12 non-neoplastic inflammatory effusions (tuberculosis, lupus erythematosus, rheumatoid arthritis, and idiopathic pleuropericarditis), and 58 neoplastic effusions (cancer of lung, breast, ovary, and pancreas, and lymphoma) were analyzed by radial immunodiffusion for orosomucoid concentration. The average concentration +/-SE was 35+/-4, 65+/-17, and 130+/-13 mg/100 ml in the three types of effusion, respectively. By gel filtration and ion exchange chromatography, orosomucoid was isolated from 12 nonmalignant and 14 malignant fluids. The orosomucoid preparations reacted as single components in acrylamide gel electrophoresis at pH 9.0, and in immunodiffusion and immunoelectrophoresis against antisera to human serum and to human plasma orosomucoid. In radial immunodiffusion, the slope of the line relating concentration to the square of the diameter of the precipitate area was identical for orosomucoid isolated from normal human plasma and from nonneoplastic effusions, but was subnormal for orosomucoid isolated from neoplastic fluids. All orosomucoid preparations had normal amino acid composition. Orosomucoid from the nonmalignant effusions had normal carbohydrate content. 11 of 14 samples of orosomucoid isolated from neoplastic fluids had abnormalities in carbohydrate composition, consisting of subnormal content of sialic acid (11 of 14), hexose (10 of 14), and hexosamine (3 of 14), and abnormally high content of hexosamine (4 of 14). Discriminant analysis showed that concentration of orosomucoid distinguished between neoplastic and nonneoplastic noninflammatory effusions more effectively than concentration of total protein, albumin, alpha(1), alpha(2), beta, or gamma-globulin.
Velocity of Blood Flow in Normal Human Venae Cavae
Authors: LEWIS WEXLER, DEREK H. BERGEL, IVOR T. GABE, GEOFFREY S. MAKIN, CHRISTOPHER J. MILLS
Journal: Circulation Research (1968)

The velocity of flow and pressure in the venae cavae of four normal conscious subjects was studied. Velocity was measured with a catheter-tip electromagnetic transducer. The effects of respiration, Valsalva and Müller maneuvers, coughing, and exercise were studied. Caval blood velocities during breath holding showed marked cardiac pulsations, being maximal at the time of ventricular systole and minimal or reversed at atrial systole. Peak velocities during ventricular systole ranged from 30 to 45 cm/sec in the inferior, and from 10 to 35 cm/sec in the superior, vena cava. A second diastolic forward flow velocity ranged from 36 to 76% of the systolic peak. During inspiration, velocity transiently increased. Reduction of flow velocity in abdominal breathing and the Müller maneuver is consistent with the formation of a local area of inferior vena caval collapse at the diaphragm. During the Valsalva maneuver, abrupt reduction in caval flow was seen that persisted throughout the strain. There was immediate overshoot when the strain was released. Coughing produced a reduction of flow velocity with backflow in the superior vena cava. In leg exercise, inferior caval flow velocity rose immediately, and it remained high during recovery. Marked respiratory velocity variations with inspiratory increases occurred during and after exercise.
Dedifferentiation Precedes Invasion in the Progression from Barrett's Metaplasia to Esophageal Adenocarcinoma
Authors: James Helm, Steven A. Enkemann, Domenico Coppola, James S. Barthel, Scott T. Kelley, Timothy J. Yeatman
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Adenocarcinoma arises in Barrett's esophagus by progression from metaplasia to cancer through grades of dysplasia. Our aim in this exploratory study was to characterize the broad changes in gene expression that underlie this histologic progression to cancer and assess the potential for using these gene expression changes as a marker predictive of malignant progression in Barrett's epithelium. Experimental Design: Microarray analysis was used to obtain individual gene expression profiles from endoscopic biopsies of nine esophageal adenocarcinomas and the Barrett's epithelia from which three of the cancers had arisen. Pooled samples from the Barrett's epithelia of six patients without cancer or dysplasia served as a reference. Results: Barrett's epithelia from which cancer had arisen differed from the reference Barrett's epithelia primarily by underexpression of genes, many of which function in governing cell differentiation. These changes in gene expression were found even in those specimens of Barrett's epithelia from which cancer had arisen that lacked dysplasia. Each cancer differed from the Barrett's epithelium from which it had arisen primarily by an overexpression of genes, many of which were associated with tissue remodeling and invasiveness. Cancers without identifiable Barrett's epithelium differed from cancers that had arisen from a Barrett's epithelium by having an even greater number of these overexpressed genes. Conclusions: Histologic progression from Barrett's epithelium to cancer is associated with a gradient of increasing changes in gene expression characterized by an early loss of gene function governing differentiation that begins before histologic change; gain in function of genes related to remodeling and invasiveness follows later. This correlation of histologic progression with increasing changes in gene expression suggests that gene expression changes in biopsies taken from Barrett's epithelium potentially could serve as a marker for neoplastic progression that could be used to predict risk for developing cancer.
High Macrophage Infiltration along the Tumor Front Correlates with Improved Survival in Colon Cancer
Authors: Johan Forssell, Åke Öberg, Maria L. Henriksson, Roger Stenling, Andreas Jung, Richard Palmqvist
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The role of macrophages in tumorigenesis is complex because they can both prevent and promote tumor development. Experimental Design: Four hundred forty-six colorectal cancer specimens were stained with the pan-monocyte/macrophage marker CD68, and average infiltration along the tumor front was semiquantitatively evaluated using a four-grade scale. Each section was similarly scored for the presence of CD68 hotspots. Some aspects of macrophage-tumor cell interactions were also studied using in vitro coculture systems. Results: Including all patients, regardless of surgical outcome and localization, survival increased incrementally with CD68TFMean infiltration grade (P = 0.0001) but not in curatively resected colon cancers (P = 0.28). CD68 hotspot score (CD68TFHotspot) was divided into high and low. A high hotspot score conferred a highly significant survival advantage also in curatively resected colon cancer cases (n = 199, P = 0.0002) but not in rectal cancers. CD68TFHotspot high turned out as an independent prognostic marker for colon cancer in multivariate analyses including gender, age, localization, grade, stage, tumor type, and lymphocytes at the tumor front, conferring a relative risk of 0.49 (P = 0.007). In vitro coculture experiments, using phorbol 12-myristate 13-acetate–activated U937 cells as macrophage model, revealed that a high ratio of macrophages to colon cancer cells inhibited cancer cell growth. This was partially dependent on cell-to-cell contact, whereas Boyden chamber cocultivation without cell-to-cell contact promoted cancer cell spread. Conclusions: In conclusion, our data indicate that a dense macrophage infiltration at the tumor front positively influences prognosis in colon cancer and that the degree of cell-to-cell contact may influence the balance between protumorigenic and antitumorigenic properties of macrophages.
Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults
Authors: Bradley C. Johnston, Steve Kanters, Kristofer Bandayrel, Ping Wu, Faysal Naji, Reed A. Siemieniuk, Geoff D. C. Ball, Jason W. Busse, Kristian Thorlund, Gordon Guyatt, Jeroen P. Jansen, Edward J. Mills
Journal: JAMA (2014)

Many claims have been made regarding the superiority of one diet or another for inducing weight loss. Which diet is best remains unclear.To determine weight loss outcomes for popular diets based on diet class (macronutrient composition) and named diet.Search of 6 electronic databases: AMED, CDSR, CENTRAL, CINAHL, EMBASE, and MEDLINE from inception of each database to April 2014.Overweight or obese adults (body mass index ≥25) randomized to a popular self-administered named diet and reporting weight or body mass index data at 3-month follow-up or longer.Two reviewers independently extracted data on populations, interventions, outcomes, risk of bias, and quality of evidence. A Bayesian framework was used to perform a series of random-effects network meta-analyses with meta-regression to estimate the relative effectiveness of diet classes and programs for change in weight and body mass index from baseline. Our analyses adjusted for behavioral support and exercise.Weight loss and body mass index at 6- and 12-month follow-up (±3 months for both periods).Among 59 eligible articles reporting 48 unique randomized trials (including 7286 individuals) and compared with no diet, the largest weight loss was associated with low-carbohydrate diets (8.73 kg [95% credible interval {CI}, 7.27 to 10.20 kg] at 6-month follow-up and 7.25 kg [95% CI, 5.33 to 9.25 kg] at 12-month follow-up) and low-fat diets (7.99 kg [95% CI, 6.01 to 9.92 kg] at 6-month follow-up and 7.27 kg [95% CI, 5.26 to 9.34 kg] at 12-month follow-up). Weight loss differences between individual diets were minimal. For example, the Atkins diet resulted in a 1.71 kg greater weight loss than the Zone diet at 6-month follow-up. Between 6- and 12-month follow-up, the influence of behavioral support (3.23 kg [95% CI, 2.23 to 4.23 kg] at 6-month follow-up vs 1.08 kg [95% CI, -1.82 to 3.96 kg] at 12-month follow-up) and exercise (0.64 kg [95% CI, -0.35 to 1.66 kg] vs 2.13 kg [95% CI, 0.43 to 3.85 kg], respectively) on weight loss differed.Significant weight loss was observed with any low-carbohydrate or low-fat diet. Weight loss differences between individual named diets were small. This supports the practice of recommending any diet that a patient will adhere to in order to lose weight.
Relationships between requests for psychiatric consultations and psychiatric diagnoses in long-term-care facilities
Authors: J P Loebel, S Borson, T Hyde, D Donaldson, C Van Tuinen, T M Rabbitt, E J Boyko
Journal: American Journal of Psychiatry (1991)

The authors' objective was to investigate reasons for referral of elderly nursing home residents for psychiatric consultation and the relationship of these reasons for referral to psychiatric diagnoses.They examined 197 nursing home residents consecutively referred to a consulting team in a university-affiliated mental health center. These patients represented all patients evaluated by the consulting team at six nursing homes over a 2-year period (Sept. 1, 1984, through Aug. 30, 1986).Reasons for referral were diverse but fell into seven broad clusters: behavioral problems; mood-related problems; consultations requested by involuntary treatment services, patients, physicians, or other referring agencies; psychotic features; physical signs; impaired activities of daily living; and other. Behavioral problems were most commonly cited and tended to be associated with dementia diagnoses. Mood-related reasons for referral were most strongly associated with diagnoses of affective disorders, and diagnoses of schizophrenia and adjustment disorder were each associated with two or more reasons for referral. However, reasons for referral were distributed widely across diagnostic groups and were relatively weak predictors of diagnoses.The results illustrate the variety of problems for which nursing home staff are willing to seek psychiatric consultation but emphasize the need for professional psychiatric evaluation to establish a diagnostic base on which treatment interventions can be built.
Evasion of Cytotoxic T Lymphocyte (CTL) Responses by <i>Nef</i>-dependent Induction of Fas Ligand (CD95L) Expression on Simian Immunodeficiency Virus–infected Cells
Authors: Xiao-Ning Xu, Gavin R. Screaton, Frances M. Gotch, Tao Dong, Rusung Tan, Neil Almond, Barry Walker, Richard Stebbings, Karen Kent, Shigekazu Nagata, Jim E. Stott, Andrew J. McMichael
Journal: The Journal of Experimental Medicine (1997)

Inoculation of macaques with live attenuated SIV strains has been shown to protect against subsequent challenge with wild-type SIV. The protective mechanism(s) remain obscure. To study the effect in more detail, we have investigated the role of virus-specific CTL responses in macaques infected with an attenuated SIV strain (pC8), which has a four–amino acid deletion in the nef gene, as compared with the wild-type SIVmac32H clone (pJ5). Cynomolgus macaques infected with pC8 were protected against subsequent challenge with pJ5 and did not develop any AIDS-like symptoms in the 12 months after infection. The pC8-induced protection was associated with high levels of virus-specific CTL responses to a variety of viral antigens. In contrast, pJ5-infected macaques had little, if any, detectable CTL response to the viral proteins after three months. The latter group of macaques also showed increased Fas expression and apoptotic cell death in both the CD4+ and CD8+ populations. In vitro, pJ5 but not pC8 leads to an increase in FasL expression on infected cells. Thus the expression of FasL may protect infected cells from CTL attack, killing viral-specific CTLs in the process, and providing a route for escaping the immune response, leading to the increased pathogenicity of pJ5. pC8, on the other hand does not induce FasL expression, allowing the development of a protective CTL response. Furthermore, interruption of the Fas-FasL interaction allows the regeneration of viral-specific CTL responses in pJ5-infected animals. This observation suggests an additional therapeutic approach to the treatment of AIDS.
The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen
Authors: Elizabeth A. Sconce, Tayyaba I. Khan, Hilary A. Wynne, Peter Avery, Louise Monkhouse, Barry P. King, Peter Wood, Patrick Kesteven, Ann K. Daly, Farhad Kamali
Journal: Blood (2005)
P75. Genetic engineering of T cells for increased homing to the tumor site
Authors: M Idorn, GH Andersen, HL Larsen, JH van den Berg, Ö Met, P thor Straten
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Adoptive cell transfer (ACT) using in vitro expanded T cells from biopsy material represents a highly promising treatment of disseminated cancer. ACT in its present form is rather crude and improvements seem within reach. Recruitment of transferred lymphocytes to the tumor site is
Circulating substance P levels and shoulder joint contracture after arthroscopic repair of the rotator cuff: Table 1
Authors: F Franceschi, U G Longo, L Ruzzini, S Morini, F Battistoni, G Dicuonzo, N Maffulli, V Denaro
Journal: British Journal of Sports Medicine (2008)

To determine the plasma levels of substance P (SP) in patients with postoperative stiffness after arthroscopic rotator cuff repair.Plasma samples were obtained at 15 months from surgery from two groups of patients who underwent arthroscopic repair of a rotator cuff tear. In group 1, 30 subjects (14 men, 16 women; mean age 64.6 years, range 47 to 78) with shoulder stiffness 15 months after arthroscopic rotator cuff repair were recruited. In group 2, 30 patients (11 men, 19 women; mean age 57.8 years, range 45 to 77) were evaluated 15 months after successful arthroscopic rotator cuff repair. Immunoassays were performed with commercially available assay kits to measure the plasma levels of SP.Plasma levels of SP in patients with postoperative stiffness were significantly greater than those in the control group (mean 81.06 (SD 27.76) versus 23.49 (5.64), p<0.05).The plasma concentrations of substance P in patients with shoulder stiffness after arthroscopic rotator cuff repair are higher compared with plasma levels of SP in patients with a good postoperative outcome. The neuronal upregulation of SP shown in the plasma of patients with postoperative shoulder stiffness may underlie not only the symptoms but also its development of adhesive capsulitis.
Biopsy Schemes with the Fewest Cores for Detecting 95% of the Prostate Cancers Detected by a 24-Core Biopsy
Authors: Vincenzo Scattoni, Marco Raber, Firas Abdollah, Marco Roscigno, Federico Dehò, Diego Angiolilli, Carmen Maccagnano, Andrea Gallina, Umberto Capitanio, Massimo Freschi, Claudio Doglioni, Patrizio Rigatti, Francesco Montorsi
Journal: European Urology (2009)