tbuckley/cabot-search huggingface dataset:
Morphogenesis of C-Type and A-Type Particles in Cells Infected by an Arbovirus
Authors: Philip M. Grimley, Irene K. Berezesky, Judith G. Levin
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Morphogenesis of C-Type and A-Type Particles in Cells Infected by an Arbovirus Get access Philip M. Grimley, Philip M. Grimley Laboratory of Pathology, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Irene K. Berezesky, Irene K. Berezesky Laboratory of Pathology, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Judith G. Levin Judith G. Levin Laboratory of Pathology, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 1, January 1973, Pages 275–279, https://doi.org/10.1093/jnci/50.1.275 Published: 01 January 1973 Article history Received: 10 October 1972 Accepted: 12 October 1972 Published: 01 January 1973
Breast Cancer Risk Factors Among Screening Program Participants
Authors: Louise A. Brinton, Roger R. Williams, Robert N. Hoover, Nancy L. Stegens, Manning Feinleib, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1979)

Data were obtained by mailed questionnaire from 405 breast cancer patients identified during the first 2 years of operation of the Breast Cancer detection Demonstration Project in the U.S. and from a sample of 1156 normal screenees (response rate = 88%) in an attempt to examine whetHer the usual risk indicators for breast cancer apply to individuals participating in screening programs. No substantial differences were found between the respondents and the nonrespondents for the variables on which information had been obtained at the time of the initial screening. Nearly all of t(e recognized risk factors were seen in this population. The relative risk (FF) of breast cancer was 3.9 among women whose mothers were also affected; this finding was statistically significant. Relative risk was increased for women reporting early menarche, late menopause, nulliparity, late age when 1st child was born, and excessive weight. The relative risk was not elevated in women with a prior breast biopsy but was excessive for those with more than 1 biopsy. No association with thyroid medications or menopausal hormones was found. Among women having undergone a natural menopause, a nonstatistically significant elevation in the relative risk was noted for long term oral contraceptive users; this excess relative risk was restricted to those using OCs in the presence of breast cancer risk indicators. The results indicate the need for further study of women with extended periods of OC use, particularly when accompanied by other known risk indicators.
DC-SIGN+ Macrophages Control the Induction of Transplantation Tolerance
Authors: Patricia Conde, Mercedes Rodriguez, William van der Touw, Ana Jimenez, Matthew Burns, Jennifer Miller, Manisha Brahmachary, Hui-ming Chen, Peter Boros, Francisco Rausell-Palamos, Tae Jin Yun, Paloma Riquelme, Alberto Rastrojo, Begoña Aguado, Joan Stein-Streilein, Masato Tanaka, Lan Zhou, Junfeng Zhang, Todd L. Lowary, Florent Ginhoux, Chae Gyu Park, Cheolho Cheong, Joshua Brody, Shannon J. Turley, Sergio A. Lira, Vincenzo Bronte, Siamon Gordon, Peter S. Heeger, Miriam Merad, James Hutchinson, Shu-Hsia Chen, Jordi Ochando
Journal: Immunity (2015)
Reducing patient eligibility criteria in cancer clinical trials.
Authors: S L George
Journal: Journal of Clinical Oncology (1996)

PURPOSE To discuss patient eligibility criteria in phase III cancer clinical trials in the larger setting of the complexity of these trials, to review the various reasons for imposing restrictive eligibility requirements, to discuss the problems caused by these requirements, to argue that these requirements should be greatly relaxed in most cancer clinical trials, to provide some guiding principles and practical suggestions to facilitate such a relaxation, and to give an example of how eligibility requirements were reduced in a recent clinical trial in acute lymphocytic leukemia. METHODS Implicit and explicit reasons for including eligibility criteria in clinical trials are reviewed. Safety concerns and sample size issues receive special attention. The types of problems restrictive eligibility criteria cause with respect to scientific interpretation, medical applicability, complexity, costs, and patient accrual are described. RESULTS A list of three items that each eligibility criterion should meet in order to be included is proposed and applied to a recent trial in acute lymphocytic leukemia. CONCLUSION Phase III clinical trials in cancer should have much broader eligibility criteria than the traditionally restrictive criteria commonly used. Adoption of less restrictive eligibility criteria for most studies would allow broader generalizations, better mimic medical practice, reduce complexity and costs, and permit more rapid accrual without compromising patient safety or requiring major increases in sample size.
Retinoblastoma protein and proliferating-cell nuclear antigen expression as predictors of recurrence in well-differentiated papillary thyroid carcinoma.
Authors: K Omura, A Nagasato, E Kanehira, H Kinsen, S Amaya, K Kimura, T Kajita, Y Nozaki, Y Mizukami, A Nonomura, Y Watanabe
Journal: Journal of Clinical Oncology (1997)

PURPOSE We analyzed retinoblastoma protein (pRB) and proliferating-cell nuclear antigen (PCNA) expression in primary tumors and recurrent lesions of well-differentiated papillary thyroid carcinoma (PTC) to clarify the relationship between their expression and recurrent disease. PATIENTS AND METHODS The study included 93 patients with PTC. No recurrent disease had developed in 60 patients within 10 years after surgery (group N). Thirty patients in whom recurrent disease had developed after surgery were enrolled in group R. Levels of pRB and PCNA expression were quantified using the CAS 200 system (Cell Analysis Systems, Elmhurst, IL) following immunohistochemical staining. RESULTS Mean pRB expression level in the primary tumors in group R was significantly lower than that in group N (P &lt; .0001). pRB expression in the tumors with a diameter up to 20 mm was significantly lower than that in tumors larger than 20 mm in group R (P &lt; .01). There were no significant differences in the levels of expression of PCNA in the primary tumors between group N and group R. Univariate analysis demonstrated that the disease-free survival was significantly correlated with pN category, pRB, and PCNA expression level. The subgroup with high-level expression of pRB (&gt; 25%) showed significantly long disease-free survival (P &lt; .001). Furthermore, the subgroup with low-level expression of PCNA (&lt; 35%) showed significantly longer disease-free survival (P &lt; .05). Multivariate analysis showed pRB expression and pN category to be independent prognostic factors for disease-free survival in PTC. CONCLUSION pRB expression level can be used as a reliable predictor for recurrence of PTC.
Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo
Authors: Anika Fischer, Sebastian Zundler, Raja Atreya, Timo Rath, Caroline Voskens, Simon Hirschmann, Rocío López-Posadas, Alastair Watson, Christoph Becker, Gerold Schuler, Clemens Neufert, Imke Atreya, Markus F Neurath
Journal: Gut (2015)

<h3>Objective</h3> Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. <h3>Design</h3> We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg<i>-Prkdcscid-Il2rgtm1Wjl</i>/SzJ) mice. <h3>Results</h3> Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. <h3>Conclusions</h3> α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion.
Effect of Blood Tamoxifen Concentrations on Surrogate Biomarkers in a Trial of Dose Reduction in Healthy Women
Authors: Andrea Decensi, Sara Gandini, Aliana Guerrieri-Gonzaga, Harriet Johansson, Lapo Manetti, Bernardo Bonanni, Maria Teresa Sandri, Antonella Barreca, Alberto Costa, Chris Robertson, Ernst A. Lien
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Tamoxifen administered at 20 mg/d has been shown to decrease breast cancer incidence in at-risk women by 50%, but toxicity may limit its broad use, particularly in postmenopausal women. Because toxicity may be dose-dependent, we studied the biologic activity of low concentrations of tamoxifen to determine the plausibility of a dose reduction. PATIENTS AND METHODS: We measured the blood concentrations of tamoxifen and its main metabolites in a dose titration study in 105 healthy women (placebo, tamoxifen 10 mg on alternate days, tamoxifen 10 mg/d, and tamoxifen 20 mg/d). Drug levels measured after 2 months of treatment were correlated with the changes in surrogate biomarkers of different diseases, including lipid profile, blood cell count, fibrinogen, antithrombin III, osteocalcin, and insulin-like growth factor I, a promising surrogate biomarker of breast cancer. RESULTS: The means (± SD) for tamoxifen and N-desmethyltamoxifen (metabolite X) concentrations (ng/mL) were dose-related, being, respectively, 0 and 0 with placebo, 26.8 ± 15.1 and 43.7 ± 22.5 with 10 mg every other day, 51.2 ± 24.1 and 90.7 ± 48.0 with 10 mg/d, and 136.0 ± 52.7 and 230.6 ± 75.0 with 20 mg/d of tamoxifen. At variance, the biomarker changes were of comparable magnitude at any drug concentration except for platelet count and triglycerides levels, the latter showing a trend to an increase with increasing tamoxifen concentrations. CONCLUSION: An 80% reduction in blood concentrations does not seem to affect the activity of tamoxifen on biomarkers of cardiovascular or breast cancer risk and may in fact have a more favorable safety profile. Additional studies are warranted to determine the most appropriate dose of this agent.
Hospital readmissions and social deprivation in asthma and COPD
Authors: Haval Balata, Robert Grecian, Sheila Grecian, Imran Aziz, Abdul Ashish
Journal: European Respiratory Journal (2013)

Background 

There have been limited studies into effects of social deprivation on readmission rates in chronic airways disease. Social factors are likely to play a role

Aims 

To study effects of social deprivation on hospital readmission rates and length of stay in asthma and COPD

Methods 

Retrospective study of all hospitalisations with a primary diagnosis of asthma or COPD, 01/11/2011-01/08/2012, in Wigan, UK. Patients were assigned an index of multiple deprivations score based on postcode then subdivided into quintiles. For each quintile, readmissions and mean length of stay (corrected per 100,000 population size) was calculated (Fishers two tailed test used for P-value). Patients from the most affluent quintile were excluded as they accounted for <5% of population

Results 

View this table:

Asthma patients





View this table:

COPD patients





11% of asthma and 32% of COPD patients were readmitted. Patients from the most deprived areas had a significantly higher number of readmissions in both conditions. However, increased length of stay in the readmitted patients was only noted with COPD

Conclusions 

Social problems appear to contribute to increased readmission rates from chronic airways disease. Investment in community/social services and cohesive working with primary care can help tackle this problem.
The efficacy of oral appliance in patients with severe obstructive sleep apnea
Authors: Önder Öztürk, Süleyman Hakan Tuna, Ulubey Hayri, Oguz Çelik, Ahmet Akkaya
Journal: European Respiratory Journal (2014)

Aim:  It has been known that the oral appliansces are effective especially in the treatment of mild to modorate obstructive sleep apnea syndrome. The aim of this study was to evaluate the effectiveness of an oral appliance (OA) “mandibular advancement devices (MADs)” for treatment of severe obstructive sleep apnea syndrome (OSAS) in patients who refused continuous positive airway pressure treatment.   Material and Methods:  The patients with the symptoms of snoring, witnessed sleep apnea and excessive daytime sleep, were evaluated by polysomnography and diagnosed as OSAS. The patients with severe OSA who refused continuous positive airway pressure (PAP) treatment were recruited. An oral appliance “mandibular advancement devices (MADs)” were prepared by the dentist. Polysomnograms with OA were repeated at the fisrt month and 6 months.The following variables were assessed: AHI, ODI, oxygen saturation at sleep, percentage of REM sleep.   Results:  Eleven patients (nine men and two woman) with mean age 53,73±2,90 years old were selected to the study. AHI and ODI were measured as 50,66± 4,46 and 54,97±2,71 respectively at baseline. OA reduced AHI significantly from 50,66 to 23,97, (p 0.05) and SatO 2  % at sleep (p>0.05).   Conclusion : Treatment with oral appliances, i.e., MADs, can be an effective in patients with severe OSAS, who refuse to use or can not tolerate PAP therapy. We think that OA can be choosen as an alternative therapy for severe OSA.
Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia.
Authors: B D Cheson, J N Frame, D Vena, N Quashu, J M Sorensen
Journal: Journal of Clinical Oncology (1998)

PURPOSE To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or high-risk CLL on the National Cancer Institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m2 per day for 5 days at monthly intervals. RESULTS Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% had high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenopathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS. CONCLUSION TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality.
Chemotherapy for Metastatic Colorectal Cancer
Authors: Joseph Rosales, Lucille A. Leong
Journal: Journal of the National Comprehensive Cancer Network (2005)

The past decade has seen a significant survival improvement for patients with metastatic colorectal cancer, fueled in large part by the arrival of active novel chemotherapeutic drugs and their incorporation into combination regimens. Several randomized trials have successfully integrated oxaliplatin and irinotecan into previously existing 5-fluorouracil (5-FU)-based regimens for advanced colorectal cancer, resulting in median survivals that have risen from 9 months to almost 2 years. Even as the ideal combinations and sequences of these regimens are elucidated, targeted therapies such as recently approved bevacizumab and cetuximab have been added to treatment protocols, with favorable consequences. We review the evolution of primary chemotherapy for advanced colorectal cancer, focusing on the trials that have led to the new standard first-line treatments. We also review the data on newer targeted therapies, especially in combination with cytotoxic therapy.
Management of Anticoagulation in Patients With Atrial Fibrillation
Authors: Joshua D. Moss, Adam S. Cifu
Journal: JAMA (2015)

Characteristics of the Guideline Source TheACC/AHATaskForceonPracticeGuidelinesdirectedand sponsored the effort without commercial support (Table). The writing committee was composed of 16 selected clinicians with expertise inadultcardiology,electrophysiology, cardiothoracic surgery, and heart failure. Writing committee members and peer reviewers were required to disclose all health care–related relationships. Neither the committee chair nor a majority of the committee members could have any relevant relationships with industry. All recommendations required approval by a consensus of the votingmembers of the committee.Members could not draft or vote on any recommendation pertaining to their industry relationships.3
Allergic bronchopulmonary aspergillosis (ABPA) prevalence in adult cystic fibrosis (CF) patients. Usefulness of recombinant Aspergillus fumigatus IgE (rAsp f) in diagnosis and monitoring treatment
Authors: Cristina Navarro, MaAndreína Perez, Dolores Hernandez, Emilio Ansotegui, Monica Cebrian, Javier Peman, Amparo Sole
Journal: European Respiratory Journal (2012)

The prevalence of ABPA in CF is variable (6-15%). Currently, the role of rAsp f in ABPA diagnosis and treatment monitoring is unknown.

Patients. Serial determinations of serum specific IgE against recombinant AF antigens were analysed yearly during 5 years in 157 adult CF patients. 19 patients fulfilled serologic criteria for ABPA, but only 9 suffered from respiratory symptoms, lung infiltrates or lung function deterioration.

Results. 9 of 157 CF patients (3 women), prevalence 6%, mean age 22 (16-33) years, BMI mean 21 (20-22). In 8/9 Delta F508 mutation was found. At time of diagnosis, 4 patients showed AF colonization, 8 had Pseudomonas aeruginosa (PA). In all patients, total IgE was higher than 500 UI/ml, and AF specific IgE was positive. Titrations for rAsp f varied, with highest titrations for rAsp f 1 and rAsp f 2. Two cases with the most torpid progress showed high titers for rAsp f 3. Lung function's distribution (FEV1) was similar in all cases.

All patients were treated with systemic corticosteroids (3 weeks and gradually reducing the dose after 3-6 months), and itraconazole/voriconazole. There were two relapses after two years, which started with respiratory symptoms.

Conclusion. In CF patients, compatible symptoms as wheezing dyspnea and functional-radiological deterioration suggest ABPA diagnosis. During treatment, only total and AF specific IgE titers, as well as lung function, served for monitoring. In our daily practice, specific AF component IgE titration does not provide diagnostic nor prognostic advantages, and neither does conventional sputum culture.
Abstract 559: Elevated Level of sCD40L During Acute Coronary Syndrome Leads to Systemic MIP-2 Release
Authors: Thomas Stadlbauer, Benedikt Molitor, Wilhelm Jochen, Petra Harwaldt, Meike Schaub, Hans Hoelschermann, Harald Tillmanns, Wolf Karsten Hofmann
Journal: Circulation (2008)

Purpose: Acute coronary syndromes (ACS) have been associated with sCD40 Ligand (sCD40L) release. Endothial cells are located at the interface between the blood and parenchymal cells and take active part in many physiological and pathologic processes, including inflammation. It has been suggested that CD40L is a key player in the pathogenesis of atherosclerosis and ACS, originating from endothelial cells. When sCD40L is present in human plasma during ACS, it is mainly derived from activated platelets. This may lead to activation of endothelial cells resulting in atherosclerosis and eventually atherothrombosis. Therefore, the aim of the present study was to investigate differential gene expression profiles of endothelial cells after stimulation with sCD40L. Methods: Human endothelial cells (HUVEC) were stimulated with sCD40L for 2 hours. Differential gene expression patterns were evaluated with Oligonucleotide microarray hybridization (UG-U133A, Affymetrix Inc, Santa Clara, CA). Significantly up-regulated gene expression was confirmed and quantitated by Real-time-PCR as well as ELISA. In serum from ACS patients expression of sCD40L was correlated with these up-regulated genes products. Results: Stimulation of HUVEC with sCD40L leads to a profound release of proinflammatory mediators like IL-8, ICAM1, ISGF3 as well as MCP-1 on a transcriptional level. In addition, gene expression profiling revealed a highly significant increase in expression of the macrophage inflammatory protein 2 (MIP-2), also known as GRO-beta or CXCL2. This was quantitated as approximately 30 fold up-regulation by real-time-PCR as well as in ELISA analysis (8 fold at 8 to 24 hours) derived from supernations. In clinical serum samples from ACS patients there was a highly significant correlation between sCD40L and MIP-2 levels (r = 0.88, p &lt; 0.01) Conclusion: Proinflammatory mediators as well as MIP-2 play an important role in the chemoattraction of macrophages, which underlines the key role of CD40L as a link between thrombotic events, e.g ACS, and inflammatory processes, e.g. atherosclerosis. Therefore targeting MIP-2 up-regulation might be a potential approach to prevent the progression of atherosclerotic diseases as well as a new therapeutic approach to treat ACS.
The relationship between sleep respiratory disorder and daytime PaO2 in OSAS and in overlap syndrome
Authors: Donato Lacedonia, Francesco Salerno, Roberto Sabato, Patrizia Guido, Lucia Forte, Giovanna E. Carpagnano, Mauro Carone, Maria P. Foschino
Journal: European Respiratory Journal (2011)

OSAS and COPD are often associated with daytime hypoxiemia. Overlap Syndrome (OS) increases the risk of daytime hypoxiemia. The aimof this study was to investigate the mechanisms which could justify the low oxygen9s levelin these patients and the effect of CPAP therapy.  563 consecutive OSAS patients were enrolled. According to pulmonary function test they were divided in 2 groups. Group 1: 473 OSAS/COPD +/-; Group 2: 90 patients OSAS/COPD +/+. All patients underwent blood gases, nocturnal polisomnography, postbronchodilator spirometry. A multivariate analysis was performed to evaluate which were the factors that determining the diurnal PaO2  The groups were matched for BMI, for age and AHI.  OS group showed lower level of daytime PaO2 compared with OSAS patients (71.6±9.7 vs 79.3±11 mmHg, p  In both groups, patients with good compliance (>4H/night) of CPAP improve daytime PaO2 (p  Our data suggest that daytime hypoxemia in OSAS patients is largely determinated by the increased of body weight. In the overlap patients daytime hypoxiemia has a more complex origin. However CPAP therapy has been shown to improve daytime PaO2 values both in OSAS than in OS patients with good compliance