tbuckley/cabot-search huggingface dataset:
Loss of Transcription Factor <i>KLF5</i> in the Context of p53 Ablation Drives Invasive Progression of Human Squamous Cell Cancer
Authors: Yizeng Yang, Hiroshi Nakagawa, Marie-Pier Tetreault, Janelle Billig, Noel Victor, Abha Goyal, Antonia R. Sepulveda, Jonathan P. Katz
Journal: Cancer Research (2011)

Squamous cell cancers account for more than half of all human cancers, and esophageal cancer is the sixth leading cause of cancer death worldwide. The majority of esophageal squamous cell carcinomas have identifiable p53 mutations, yet the same p53 mutations are found at comparable frequencies in precancerous dysplasia, indicating that transformation requires additional somatic changes yet to be defined. Here, we show that the zinc finger transcription factor Krüppel-like factor 5 (KLF5) transactivates NOTCH1 in the context of p53 mutation or loss. KLF5 loss limited NOTCH1 activity and was sufficient on its own to transform primary human keratinocytes harboring mutant p53, leading to the formation of invasive tumors. Restoration of NOTCH1 blocked transformation of KLF5-deficient and p53-mutant keratinocytes. Although human dysplastic epithelia accumulated KLF5, KLF5 expression was lost concurrently with NOTCH1 in squamous cell cancers. Taken together, these results define KLF5 loss as a critical event in squamous cell transformation and invasion. Our findings suggest that KLF5 may be a useful diagnostic and therapeutic target in esophageal squamous carcinomas and possibly more generally in other cancers associated with p53 loss of function.
Phase II Study of Rituximab in Combination With CHOP Chemotherapy in Patients With Previously Untreated, Aggressive Non-Hodgkin’s Lymphoma
Authors: J. M. Vose, B. K. Link, M. L. Grossbard, M. Czuczman, A. Grillo-Lopez, P. Gilman, A. Lowe, L. A. Kunkel, R. I. Fisher
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, South San Francisco, CA) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Thirty-three patients with previously untreated advanced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m 2 per dose) on day 1 of each cycle in combination with six doses of CHOP chemotherapy given on day 3 of each cycle. RESULTS: The ORR by investigator assessment confirmed by the sponsor was 94% (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients were classified as having progressive disease. In the 18 patients with an International Prognostic Index (IPI) score ≥ 2, the combination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%. The median duration of response and time to progression had not been reached after a median observation time of 26 months. Twenty-nine of 31 responding patients remained in remission during this follow-up period, including 15 of 16 patients with an IPI score ≥ 2. The most frequent adverse events attributed to Rituxan were fever and chills, primarily during the first infusion. Rituxan did not seem to compromise the ability of patients to tolerate CHOP; all patients completed the entire six courses of the combination. The bcl-2 translocation of blood or bone marrow was positive at baseline in 13 patients; 11 patients had follow-up specimens obtained (eight CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission. CONCLUSION: This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard-dose CHOP in the treatment of aggressive B-cell lymphoma. The clinical responses are at least comparable to those achieved with CHOP alone with no significant added toxicity. The presence or absence of the bcl-2 translocation did not affect the ability of patients to achieve a CR with this regimen. The ability to achieve sustained remissions in patients with an IPI score ≥ 2 warrants further investigation with a randomized study.
Molecular Predictors of Outcome With Gefitinib and Docetaxel in Previously Treated Non–Small-Cell Lung Cancer: Data From the Randomized Phase III INTEREST Trial
Authors: Jean-Yves Douillard, Frances A. Shepherd, Vera Hirsh, Tony Mok, Mark A. Socinski, Radj Gervais, Mei-Lin Liao, Helge Bischoff, Martin Reck, Mark V. Sellers, Claire L. Watkins, Georgina Speake, Alison A. Armour, Edward S. Kim
Journal: Journal of Clinical Oncology (2009)

PURPOSE In the phase III INTEREST trial, 1,466 pretreated patients with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes. METHODS Biomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations. Results For all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel, with no statistically significant differences between treatments and no significant treatment by biomarker status interaction tests. EGFR mutation-positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib versus docetaxel. CONCLUSION These biomarkers do not appear to be predictive factors for differential survival between gefitinib and docetaxel in this setting of previously treated patients; however, subsequent treatments may have influenced the survival results. For secondary end points of PFS and ORR, some advantages for gefitinib over docetaxel were seen in EGFR mutation-positive and high EGFR copy number patients. There was no statistically significant difference between gefitinib and docetaxel in biomarker-negative patients. This suggests gefitinib can provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers such as mutation status may additionally identify which patients are likely to gain greatest PFS and ORR benefit from gefitinib.
Age, height and weight of female Olympic finalists in running events.
Authors: T Khosla
Journal: British Journal of Sports Medicine (1985)

Age, height, weight and body mass index (weight/height2) of women finalists from seven running events (100 m, 200 m, 400 m, 800 m, 1500 m, 3000m and marathon) are analysed. The data on 174 runners are derived from four Olympics (Munich, Montreal, Moscow and Los Angeles). On average endurance runners (3000 m and marathon are 4.8 years older, 6 cm shorter and 5 kg lighter for their height than sprinters (200 m and 400 m). A consistent trend of decreasing body mass index with run was observed; adjusting for height the marathon runners were 7 kg lighter than 100 m sprinters.
The Basic and Clinical Pharmacology of Nonpeptide Vasopressin Receptor Antagonists
Authors: M Thibonnier, P Coles, A Thibonnier, M Shoham
Journal: The Annual Review of Pharmacology and Toxicology (2001)

The neurohypophysial hormone arginine vasopressin (AVP) is a cyclic nonpeptide whose actions are mediated by the stimulation of specific G protein–coupled membrane receptors pharmacologically classified into V 1 -vascular (V 1 R), V 2 -renal (V 2 R) and V 3 -pituitary (V 3 R) AVP receptor subtypes. The random screening of chemical compounds and optimization of lead compounds recently resulted in the development of orally active nonpeptide AVP receptor antagonists. Potential therapeutic uses of AVP receptor antagonists include (a) the blockade of V 1 -vascular AVP receptors in arterial hypertension, congestive heart failure, and peripheral vascular disease; (b) the blockade of V 2 -renal AVP receptors in the syndrome of inappropriate vasopressin secretion, congestive heart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hyponatremia; (c) the blockade of V 3 -pituitary AVP receptors in adrenocorticotropin-secreting tumors. The pharmacological and clinical profile of orally active nonpeptide vasopressin receptor antagonists is reviewed here.
Large measles epidemic in Switzerland from 2006 to 2009: consequences for the elimination of measles in Europe
Authors: J L Richard, V Masserey Spicher
Journal: Eurosurveillance (2009)

Switzerland adheres to the objective of eliminating measles within the European region of the World Health Organization (WHO) by 2010. After several years with a relatively low annual incidence rate (0.3 to 1 case per 100,000 inhabitants), there has been a large epidemic of measles from November 2006 to August 2009. By mid September 2009, 4,415 cases were notified by physicians and laboratories, corresponding to an incidence rate of 15 per 100,000 in 2007 and 29 per 100,000 in 2008; by far the highest rates in Europe. This exceptionally long nationwide epidemic comprised three successive waves, with peaks in August 2007 (171 cases), March 2008 (569 cases) and March 2009 (417 cases). It mainly affected children aged from five to 14 years (48% of cases). Most cases were not vaccinated (93%) or were incompletely vaccinated (5%). In total 656 patients (15%) suffered complications or were hospitalised. Insufficient, spatially heterogeneous immunisation coverage (87% for at least one dose at the age of two years at the national level) has allowed a sequence of numerous outbreaks to occur, despite the gradual strengthening of measures to control the disease. Several exportations to Europe (81 in 2007 and 2008) and to the rest of the world (10 for the whole of the epidemic) have in some instances caused large outbreaks. The epidemic was a threat to the goal of eliminating measles in Switzerland and in Europe. The Federal Office of Public Health (FOPH) and its partners are currently working on a national strategy to eliminate measles.
Relationship between active inflammatory lesions in the spine and sacroiliac joints and new development of chronic lesions on whole-body MRI in early axial spondyloarthritis: results of the ESTHER trial at week 48
Authors: I.-H. Song, K. G. Hermann, H. Haibel, C. E. Althoff, D. Poddubnyy, J. Listing, A. Weiss, B. Freundlich, M. Rudwaleit, J. Sieper
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Aim</h3> To investigate the relationship between active inflammatory lesions on whole-body MRI (wb-MRI) and new development of chronic lesions on T1 MRI in patients with early axial spondyloarthritis (SpA) treated either with etanercept (ETA) or sulfasalazine (SSZ). <h3>Methods</h3> Wb-MRIs of 65 patients treated either with ETA (n=35) or SSZ (n=30) over 1 year were scored for active inflammation, fatty lesions, erosions and ankylosis in the 23 vertebral units (VUs) of the spine and in the sacroiliac joints (SI joints). Scoring was performed by two blinded radiologists. <h3>Results</h3> If there was no previous inflammation in the bone no new fatty lesions occurred in SI joint quadrants and only a few (0.6%) in spine VUs. There was a significant relationship between disappearance of inflammation and the appearance of fatty lesions: if baseline inflammation resolved fatty lesions occurred in 10.5% of SI joint quadrants and 17.9% of VUs. If inflammation did not resolve over 1 year, fatty lesions occurred less frequently: 2.4% (SI joint quadrants) and 7.2% (VUs). There was a significantly higher increase of the mean fatty lesion score between baseline and week 48 in the ETA (4.0 vs 4.8 for the SI joints and 1.9 vs 2.7 for the spine) compared to the SSZ (3.0 vs 3.2 for the SI joints and 1.1 vs 1.2 for the spine, respectively) group (p=0.001 and p=0.020 for the differences). No significant changes in the erosion or ankylosis score were observed in any of the two groups during this time. <h3>Conclusions</h3> These data indicate that there is a close interaction between inflammation, tumour necrosis factor blockade and the development of fatty lesions in subchondral bone marrow of patients with axial SpA.
Periarthritis of the shoulder and diabetes mellitus.
Authors: J F Bridgman
Journal: Annals of the Rheumatic Diseases (1972)

Periarthritis of the shoulder (frozen shoulder) is a well-defined condition with its phases of severe pain, increasing stiffness, and the gradual recovery of full movement of the shoulder; these features usually occur over a number of months.The aetiology of this condition, however, is not clearly understood.Amongst the factors suggested are trauma (Charnley,
Photodynamic therapy based on 5‐aminolevulinic acid and its use as an antimicrobial Agent
Authors: Frederick Harris, Lynne Pierpoint
Journal: Medicinal Research Reviews (2011)

Abstract Exogenous 5‐aminolevulinic acid (ALA) is taken up directly by bacteria, yeasts, fungi, and some parasites, which then induces the accumulation of protoporphyrin IX (PPIX). Subsequent light irradiation of PPIX leads to the inactivation of these organisms via photodamage to their cellular structures. ALA uptake and light irradiation of PPIX produced by host cells leads to the inactivation of other parasites, along with some viruses, via the induction of an immune response. ALA‐mediated PPIX production by host cells and light irradiation result in the inactivation of other viruses via either the induction of a host cell response or direct photodynamic attack on viral particles. This ALA‐mediated production of light‐activated PPIX has been extensively used as a form of photodynamic therapy (PDT) and has shown varying levels of efficacy in treating conditions that are associated with microbial infection, ranging from acne and verrucae to leishmaniasis and onychomycosis. However, for the treatment of some of these conditions by ALA‐based PDT, the role of an antimicrobial effect has been disputed and in general, the mechanisms by which the technique inactivates microbes are not well understood. In this study, we review current understanding of the antimicrobial mechanisms used by ALA‐based PDT and its role in the treatment of microbial infections along with its potential medical and nonmedical applications.
Factitious skin lesions in a mother and two sons
Authors: L. STANKLER
Journal: British Journal of Dermatology (1977)

A family is described in which a woman, probably in a state of ‘hysterical conversion’, produced factitious lesions in her own skin (dermatitis artefacta) and in the skin of two sons (child abuse). Non-accidental injury to a child's skin may form part of a spectrum of skin artefacts in the parent.
Early Statin Initiation and Outcomes in Patients With Acute Coronary Syndromes
Authors: L. Kristin Newby
Journal: JAMA (2002)

The secondary prevention benefit of therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly demonstrated; however, the role of early initiation of statins after acute coronary syndromes (ACSs) is unknown.To evaluate the association of early statin initiation (< or = 7 days) after ACS with 90-day and 1-year outcomes.Observational cohort from databases of 2 randomized clinical trials, SYMPHONY and 2nd SYMPHONY.Nine hundred thirty-one clinical centers in 37 countries.A total of 12,365 ACS patients randomized from August 1997 to August 1999 who were not taking statins prior to the index ACS and who either started statin therapy early (median, 2.0 [interquartile range, 1.0-3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never received statin therapy (n = 8413).Ninety-day incidence of death; death or myocardial infarction (MI); and death, MI, or severe recurrent ischemia; as well as 1-year incidence of death.Ninety-day and 1-year unadjusted mortality comparison suggested early statin benefit (1.2% for early statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92-1.18). After propensity and covariate adjustment, there were no 90-day or 1-year differences between the early-statin group and the no-statin group. The 90-day adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95% CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI, 0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among 2711 patients with core laboratory lipid analysis, early statin was associated with higher adjusted risk for death or death or MI at cholesterol levels below treatment guidelines but was more favorable at higher levels.In this study, there was no relationship between early initiation of statin therapy and improved outcomes although our subset analysis suggests that outcomes after early statin initiation may vary with cholesterol levels. Confirmation of early treatment effects of statins on outcomes awaits the results of adequately powered randomized clinical trials.
The Need for Reform of the Medical Examination System
Authors: T. P. Teale
Journal: BMJ (1896)

Finially, the Committee make various recommendations with a view to amend the present system, and have given a brief summary of thenm.[This is reproduced in the report of the meeting at page I415.]I think that you will con-clude witlh me that notlhing could be more satisfactory thani the expressioni of opillion wlhicl eInaItated from the Select Committee.Desirous to see some practical result arising therefrom, it was deemed desirable in the following year again to approaclh Mr. Asquith, and to learn what steps, if any, were to be taken for the purpose of carrying it into effect.A deputation from the British Medical Association on several medical subjects was received, and Sir Walter Foster was on this occasion associated with the Home -Secretary, in connection especially with the present subject.Botlh replied favourably to our statements and inquiry, and it wvas uniderstood that the Local Government Board might be expected to move in the matter alnd prepare a Bill to carry out the recommendations of the Committee.However, not very long after all tllis had been accomplished a change of Ministry, as we all know, took place, n-ecessarily puttinig anl end to the business for a eonsiderable period.But many of us think that the time lhas niow arrived for taking some-further action to obtain the object in question, whiclh is -not one involvinig any very serious labour or difficulty, seeing that the evidence is so complete and h2s beein already so well coni §idered.Then lhappily also this is niot a party question.All that appears to be niecessary at present, so far as I can learn, is that we should forward a memorial to Her Majesty's Secretary of State for the Home Department, witlh a request that 1he will consider the important wvork whicl has been already done by the Select Committee alnd lhas beein so clearly set fortlh for the purpose; and if hie sees fit, that he will take steps to embody their recommendations in an Act of Par-.liament with such modifications or additions, if any, as may be inl his judgment desirable, for the purpose of givinlg thle country a greatly improved procedure ill exchange for that whiclh is at presenit employed.
Regional Brain Activation during Verbal Declarative Memory in Metastatic Breast Cancer
Authors: Shelli R. Kesler, F. Chris Bennett, Misty L. Mahaffey, David Spiegel
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To determine the neurofunctional basis of verbal memory dysfunction in women with metastatic breast cancer. This objective was based on previous research suggesting memory and other cognitive deficits in this population. We attempted to determine if verbal memory impairments were related to the most commonly studied disease parameters including adjuvant chemotherapy and chronic stress-related disruption of limbic system structures. Experimental Design: We used functional magnetic resonance imaging to test our hypothesis that women with breast cancer would show significantly lower brain activation during verbal declarative memory tasks compared with age and education-matched healthy female controls. We also assessed several stress-related variables including diurnal cortisol levels to test our hypothesis that women with breast cancer would show higher stress and this would contribute to brain activation deficits during memory tasks. Results: Women with breast cancer had significantly lower prefrontal cortex activation during the memory encoding condition compared with controls. However, the breast cancer group showed significantly greater activation than controls during the recall condition in multiple, diffuse brain regions. There were no significant differences between the groups in stress-related variables. Women who were treated with cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy showed lower prefrontal cortex activation during memory encoding. Conclusions: These results suggest that women with metastatic breast cancer may be at risk for verbal memory impairments as a result of altered functional brain activation profiles. These findings may be associated with chemotherapy type and/or other aspects of the breast cancer disease process. (Clin Cancer Res 2009;15(21):6665–73)
Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre in sub-Saharan Africa: a prospective descriptive autopsy study
Authors: Matthew Bates, Victor Mudenda, Aaron Shibemba, Jonas Kaluwaji, John Tembo, Mwila Kabwe, Charles Chimoga, Lophina Chilukutu, Moses Chilufya, Nathan Kapata, Michael Hoelscher, Markus Maeurer, Peter Mwaba, Alimuddin Zumla
Journal: The Lancet Infectious Diseases (2015)
Suppressive mechanisms of alveolar macrophages in interstitial lung diseases: role of soluble factors and cell-to-cell contact
Authors: E Fireman, S Ben-Efraim, S Spinrad, M Topilsky, J Greif
Journal: European Respiratory Journal (1993)

Alveolar macrophages (AMs) from patients with interstitial lung diseases, such as sarcoidosis and idiopathic pulmonary fibrosis, suppress the phytohaemagglutinin (PHA) stimulation of autologous peripheral lymphocytes. The aim of this study was to determine whether the suppressive effect of alveolar macrophages of patients with interstitial lung disease is due, not only to the secretion of soluble factors prostaglandin E2 (PGE2), interleukin-1 (IL-1) but is also correlated to a direct effect of AMs on the expression of IL-2 receptors (IL-2R: CD25) and on the induction of IL-2 activity. We studied 26 subjects, 8 with sarcoidosis, 7 with idiopathic pulmonary fibrosis, and 11 controls. Alveolar macrophages of sarcoid and idiopathic pulmonary fibrosis patients suppressed proliferation of autologous peripheral lymphocytes by 68 +/- 14% and 53 +/- 4.5%, respectively, compared to enhancement of 19 +/- 11% in three controls and suppression of 25 +/- 11% in the other six controls; the difference between subjects with interstitial lung disease and controls was significant. As already reported, the alveolar macrophages of sarcoid patients secreted large amounts of IL-1 (184 +/- 59 U.ml-1) whereas the alveolar macrophages from idiopathic pulmonary fibrosis patients secreted large amounts of PGE2 (3.6 +/- 2 ng.ml-1 x 10(-5) cells) compared with 23 +/- 19 U.ml-1 IL-1 and 0.34 +/- 0.15 ng.ml-1 x 10(-5) cells respectively, of controls. Suppression by supernatants recovered from lipopolysaccharide (LPS) stimulated alveolar macrophages can only partially explain the high suppressive effect of alveolar macrophages of interstitial lung diseases.(ABSTRACT TRUNCATED AT 250 WORDS)