tbuckley/cabot-search huggingface dataset:
Myeloid-Derived Suppressor Cells as Osteoclast Progenitors: A Novel Target for Controlling Osteolytic Bone Metastasis
Authors: Anandi Sawant, Selvarangan Ponnazhagan
Journal: Cancer Research (2013)

Immune cells and their secreted growth factors play major roles in tumor growth and metastasis. Interplay between the growing tumor and infiltrating immune cells determines the nature of immune response and ultimately, tumor fate. Increased infiltration of protumorigenic immune cells promotes tumor growth as well as dissemination to distant sites. These cells induce immunosuppression that inhibits proliferation and functions of cells of antitumor immune response. One population of immunosuppressive cells that is increasingly gaining attention is myeloid-derived suppressor cells (MDSC). MDSCs are immature myeloid progenitors that suppress T-cell effector functions and promote angiogenesis. MDSC numbers are elevated at both the primary tumor and metastatic sites, including bone. In addition to immunosuppressive functions of MDSCs, we and others have recently discovered a novel function for MDSCs as osteoclast progenitors. Osteolysis is a common complication in the carcinomas of breast, lung, prostate, and multiple myeloma with poor prognosis. Therefore, targeting the functions of MDSCs may exert dual therapeutic effects on immunosuppression and bone pathology. Cancer Res; 73(15); 4606-10. ©2013 AACR.
Agranulocytosis during antibiotic therapy: Drug sensitivity or sepsis?
Authors: Anthony V. Pisciotta
Journal: American Journal of Hematology (1993)

Abstract Forty‐three patients reviewed from the literature and five cases of agranulocytosis during antibiotic therapy studied by the author are presented. Time required to develop agranulocytosis with antibiotics was &lt;19 days in comparison to &gt;40 days required with nonantibiotic drugs. In all, agranulocytosis occurred concomitantly with drug treatment and became normal as treatment was discontinued. Retrospective rechallenge studies suggest that agranulocytosis may be dose related. In all cases PMNs were almost completely deleted and marrows were devoid of granulocyte precursors. In contrast, leukopenia secondary to overwhelming sepsis displayed persisting granulocytes in peripheral blood and marrow. While leukagglutinins were not found in nine cited cases, four serums were toxic to test PMNs as measured by suppression of postphagocytosis respiratory burst. Clindamycin directly suppressed development of CFU‐G in one sensitive patient but not in 16 normal controls. The hazard of antibiotics in suppressing granulocytopoiesis is emphasized by these observations. © 1993 Wiley‐Liss, Inc.
Use FEV6 and FEV1/FEV6 as alternative indicators in the diagnosis of bronchial obstruction in primary care
Authors: Ganna Stupnytska
Journal: European Respiratory Journal (2013)

Background. We know that the spirometry is recommended for the diagnosis and management of chronic obstructive pulmonary disease (COPD). The specialists of respiratory medicine such as the American Thoracic and European Respiratory Societies (ATS/ERS) have published guidelines on standards of spirometry.  Materials and Methods  We analyzed data of lung function test of adult patients with and without COPD. Spirometry was performed with a mass flow sensor (BTL 08- Spiro; UK) according to the guidelines of the European Respiratory Society. For the diagnosis of airway obstruction, we used the NHANES III reference equations to calculate the LLN for FEV1, FEV6, FVC, FEV1/FEV6, and FEV1/FVC. We calculated sensitivity and specificity for FEV1/FEV6 below its LLN as a predictor for obstruction. We calculated the positive predictive value (PPV) and negative predictive value (NPV).  Results. We analysed data of 250 spirometric test results in patients with COPD, 200 healthy who do not smoke and 245, who had an experience of smoking more than 33 packyears. Parameters of FEV6 and FEV1/FEV6 ratio in patients with COPD were similar to FVC and FEV1/FVC. The FEV1/FEV6 sensitivity was 92.0% and specificity was 90.1%. The PPV of FEV1/FEV6 was 88.6%, and the NPV was 92.0%. The prevalence of obstruction was 368 of 645 subjects (57.1%).  Conclusion. The FEV1/FEV6 ratio can be used as a valid alternative for FEV1/FVC in the diagnosis of airway obstruction in adults when the realization of the broncodilatation test is limited in screening study in primary care.
MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
Authors: Kar Lok Kong, Dora Lai Wan Kwong, Tim Hon-Man Chan, Simon Ying-Kit Law, Leilei Chen, Yan Li, Yan-Ru Qin, Xin-Yuan Guan
Journal: Gut (2011)

<h3>Background</h3> To understand the involvement of micro-RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues. <h3>Methods</h3> miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of <i>miR-375</i> in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of <i>miR-375</i>. The tumour-suppressive effect of <i>miR-375</i> was determined by both in-vitro and in-vivo assays. <h3>Results</h3> The downregulation of <i>miR-375</i> was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p&lt;0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of <i>miR-375</i> was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that <i>miR-375</i> could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that <i>miR-375</i> could interact with the 3′-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with <i>miR-375</i> expression (p=0.008). <h3>Conclusions</h3> This study demonstrates that <i>miR-375</i> has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of <i>miR-375</i>, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.
Mechanoelectrical Transduction by Hair Cells in the Acousticolateralis Sensory System
Authors: A J Hudspeth
Journal: Annual Review of Neuroscience (1983)

Hair cells are sensory receptors that occur ubiquitously in the vertebrate sensory organs, collectively constituting the acousticolateralis system, re­ sponsible for the detection of sound, linear and angular accelerations, water motion, and substrate vibration. In subserving these various sensitivities, hair cells occur in organs of widely di1fering structures and of frequency sensitivities covering the range 0-100 kHz. Despite this variability of envi­ ronment and function, however, all hair cells share a sensory apparatus of similar structure and all seem to operate in fundamentally the same manner. This paper describes the structure of the sensory apparatus of hair cells and what is known of their  process. In the context of the acousticolateralis system, the term transduction is employed with both a broad and a narrow meaning. In the general sense,  is taken to include the whole complex of events-acoustical, mechanical, hydrodynamic, and physiological-that occur between the ap­ plication of stimuli and genesis of a neural response. The present review focuses on  in its more restricted, cellular sense, as the transfor­ mation of a mechanical stimulus into a conductance change and an elec­ trical response of the hair cell's membrane. Because the number of publications addressing this point is fairly restricted, and since there have
Weighing the Evidence for Expanding Physician Supply
Authors: Richard A. Cooper
Journal: Annals of Internal Medicine (2004)

For 2 decades, health planners have forecasted impending physician surpluses, and policy decisions related to medical schools and residency programs have been based on such expectations. However, these much-heralded surpluses never materialized, and a growing body of data and opinion now point in the other direction. The question at the forefront is whether the United States is instead headed for a physician shortage. What is the evidence? This paper reviews the trends that link economic growth to health care spending and to the demand for physicians. It assesses the current environment by examining trends in the characteristics of clinical practice, signals from the medical market, and recent experiences of physician shortages in other English-speaking countries; it also discusses why past forecasting approaches may have failed. Taken together, this body of information indicates that physician shortages are emerging and that they will probably worsen over the next 2 decades. By 2020 or 2025, the deficit could be as great as 200 000 physicians—20% of the needed workforce. If remedies are to be found, the nature of the problem must be appreciated, and a consensus to solve it must be reached.
Phase I Study of Accelerated Conformal Radiotherapy for Stage I Non–Small-Cell Lung Cancer in Patients With Pulmonary Dysfunction: CALGB 39904
Authors: Jeffrey A. Bogart, Lydia Hodgson, Stephen L. Seagren, A. William Blackstock, Xiaofei Wang, Robert Lenox, Andrew T. Turrisi, John Reilly, Ajeet Gajra, Everett E. Vokes, Mark R. Green
Journal: Journal of Clinical Oncology (2009)

Purpose The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined. Patients and Methods Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (&lt; 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted.
PPM1D Mutations in Circulating White Blood Cells and the Risk for Ovarian Cancer
Authors: Mohammad R. Akbari, Pierre Lepage, Barry Rosen, John McLaughlin, Harvey Risch, Mark Minden, Steven A. Narod
Journal: JNCI Journal of the National Cancer Institute (2013)

We compared the frequency of PPM1D mutation in the white blood cells from 1295 ovarian cancer case patients and 834 control subjects. We found a truncating mutation in 20 case patients vs 1 control subject (odds ratio [OR] = 13.07; 95% confidence interval [CI] = 1.75 to 97.55; P < .001). The 12-year mortality of the PPM1D -positive case patients was higher than that of the PPM1D -negative case patients (hazard ratio = 2.02; 95% CI = 1.21 to 3.39; P = .007). Three of the 20 PPM1D carrier case patients had a past history of breast cancer compared with 29 of 1129 noncarriers (OR = 6.69; 95% CI = 1.86 to 24.11; P = .007). The lifetime risks for breast or ovarian cancer among female first-degree relatives of PPM1D mutation carriers were not increased compared with that of case patients without mutations. These observations suggest PPM1D mutations in the mosaic state predispose women to breast and ovarian cancer in the absence of a family history of cancer.
Respiratory function among Malaysian aboriginals
Authors: A. E. Dugdale, J. M. Bolton, A. Ganendran
Journal: Thorax (1971)

Respiratory function tests have been performed on 43 Malaysian aboriginals. The forced vital capacity and forced expiratory volume in one second (FEV<sub>1</sub>) were considerably below, and the peak expiratory flow rate (PEFR) slightly below, the predicted values. The FEV<sub>1</sub> and PEFR decreased more rapidly with advancing age than predicted from western standards. These findings may be due to physiological differences or may be the result of chronic purulent bronchitis which is common among the aboriginals.
Inhalation challenges with agents causing occupational asthma
Authors: O Vandenplas, JL Malo
Journal: European Respiratory Journal (1997)

Occupational asthma (OA) is steadily emerging as the principal cause of respiratory disease due to the workplace environment. One of the key means to ascertain diagnosis of OA is specific inhalation challenge (SIC) with occupational agents. This review: 1) describes the methodology of SIC, with a special emphasis on procedures aimed at increasing the safety and validity of these tests; and 2) outlines the roles of SIC in the diagnosis of OA in clinical and medicolegal assessment, epidemiological studies, surveillance programmes and the investigation of the pathophysiological mechanisms of asthma and OA. We discuss areas of future development, including the development of apparatus which allows exposure of subjects to low and stable concentrations of the occupational agent and the assessment of preventive procedures.
TNF-α reduces PGC-1α expression through NF-κB and p38 MAPK leading to increased glucose oxidation in a human cardiac cell model
Authors: Xavier Palomer, David Álvarez-Guardia, Ricardo Rodríguez-Calvo, Teresa Coll, Juan C. Laguna, Mercy M. Davidson, Tung O. Chan, Arthur M. Feldman, Manuel Vázquez-Carrera
Journal: Cardiovascular Research (2008)

Inflammatory responses in the heart that are driven by sustained increases in cytokines have been associated with several pathological processes, including cardiac hypertrophy and heart failure. Emerging data suggest a link between cardiomyopathy and myocardial metabolism dysregulation. To further elucidate the relationship between a pro-inflammatory profile and cardiac metabolism dysregulation, a human cell line of cardiac origin, AC16, was treated with tumour necrosis factor-α (TNF-α). Exposure of AC16 cells to TNF-α inhibited the expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α), an upstream regulator of lipid and glucose oxidative metabolism. Studies performed with cardiac-specific transgenic mice (Mus musculus) overexpressing TNF-α, which have been well characterized as a model of cytokine-induced cardiomyopathy, also displayed reduced PGC-1α expression in the heart compared with that of control mice. The mechanism by which TNF-α reduced PGC-1α expression in vitro appeared to be largely mediated via both p38 mitogen-activated protein kinase and nuclear factor-κB pathways. PGC-1α downregulation resulted in an increase in glucose oxidation rate, which involved a reduction in pyruvate dehydrogenase kinase 4 expression and depended on the DNA-binding activity of both peroxisome proliferator-activated receptor β/δ and estrogen-related receptor α transcription factors. These results point to PGC-1α downregulation as a potential contributor to cardiac dysfunction and heart failure in metabolic disorders with an inflammatory background.
Mathematical principles of reinforcement
Authors: Peter R. Killeen
Journal: Behavioral and Brain Sciences (1994)

Abstract Effective conditioning requires a correlation between the experimenter's definition of a response and an organism's, but an animal's perception of its behavior differs from ours. These experiments explore various definitions of the response, using the slopes of learning curves to infer which comes closest to the organism's definition. The resulting exponentially weighted moving average provides a model of memory that is used to ground a quantitative theory of reinforcement. The theory assumes that: incentives excite behavior and focus the excitement on responses that are contemporaneous in memory. The correlation between the organism's memory and the behavior measured by the experimenter is given by coupling coefficients, which are derived for various schedules of reinforcement. The coupling coefficients for simple schedules may be concatenated to predict the effects of complex schedules. The coefficients are inserted into a generic model of arousal and temporal constraint to predict response rates under any scheduling arrangement. The theory posits a response-indexed decay of memory, not a time-indexed one. It requires that incentives displace memory for the responses that occur before them, and may truncate the representation of the response that brings them about. As a contiguity-weighted correlation model, it bridges opposing views of the reinforcement process. By placing the short-term memory of behavior in so central a role, it provides a behavioral account of a key cognitive process.
Cardiac Memory Is Associated With Decreased Levels of the Transcriptional Factor CREB Modulated by Angiotensin II and Calcium
Authors: Kornelis W. Patberg, Alexei N. Plotnikov, Aaron Quamina, Ravil Z. Gainullin, Andrew Rybin, Peter Danilo, Lena S. Sun, Michael R. Rosen
Journal: Circulation Research (2003)

Cardiac memory (CM) has short- (STCM) and long-term (LTCM) components modulated by calcium and angiotensin II. LTCM is associated with reduced Ito and Kv4.3 mRNA levels. Because the cAMP response element binding protein, CREB, contributes to CNS memory transcription, we hypothesized that it might be a transcriptional factor in CM, influenced by calcium and angiotensin II. We studied STCM in dogs that were AV sequentially paced (AVP) for 2 hours or sham-operated. STCM was evaluated with ECG and vectorcardiogram (VCG), and subepicardial biopsies were taken at 5 to 120 minutes and investigated for CREB. LTCM was studied in dogs paced for 3 weeks and in sham controls. At 3 weeks the heart was excised, biopsies obtained, and CRE binding tested. STCM induction occurred in AVP dogs but not in sham or AVP dogs treated with saralasin or nifedipine. Nuclear CREB was significantly decreased at 2 hours in the AVP no-drug group only. LTCM dogs manifested reduced binding of nuclear proteins to CRE, and CRE binding activity in the promoter region of Kv4.3. In conclusion, there is an association between STCM induction and decreased nuclear CREB that is angiotensin-modulated and calcium-dependent. Moreover, the decreased CRE binding after 3 weeks of AVP combined with CRE binding activity in the Kv4.3 promoter can explain the Kv4.3 mRNA and Ito downregulation that characterize LTCM.
Second Malignant Neoplasms in Survivors of Pediatric Hodgkin's Lymphoma Treated With Low-Dose Radiation and Chemotherapy
Authors: Maureen M. O'Brien, Sarah S. Donaldson, Raymond R. Balise, Alice S. Whittemore, Michael P. Link
Journal: Journal of Clinical Oncology (2010)

Survivors of childhood Hodgkin's lymphoma (HL) are at risk for second malignant neoplasms (SMNs). It is theorized that this risk may be attenuated in patients treated with lower doses of radiation. We report the first long-term outcomes of a cohort of pediatric survivors of HL treated with chemotherapy and low-dose radiation.Pediatric patients with HL (n = 112) treated at Stanford from 1970 to 1990 on two combined modality treatment protocols were identified. Treatment included six cycles of chemotherapy with 15 to 25.5 Gy involved-field radiation with optional 10 Gy boosts to bulky sites. Follow-up through September 1, 2007, was obtained from retrospective chart review and patient questionnaires.One hundred ten children completed HL therapy; median follow-up was 20.6 years. Eighteen patients developed one or more SMNs, including four leukemias, five thyroid carcinomas, six breast carcinomas, and four sarcomas. Cumulative incidence of first SMN was 17% (95% CI, 10.5 to 26.7) at 20 years after HL diagnosis. The standard incidence ratio for any SMN was 22.9 (95% CI, 14.2 to 35) with an absolute excess risk of 93.7 cases per 10,000 person-years. All four secondary leukemias were fatal. For those with second solid tumors, the mean (+/- SE) 5-year disease-free and overall survival were 76% +/- 12% and 85% +/- 10% with median follow-up 5 years from SMN diagnosis.Despite treatment with low-dose radiation, children treated for HL remain at significant risk for SMN. Sarcomas, breast and thyroid carcinomas occurred with similar frequency and latency as found in studies of children with HL who received high-dose radiation.
Hepatocellular Carcinoma Risk Prediction Model for the General Population: The Predictive Power of Transaminases
Authors: Chi-Pang Wen, Jie Lin, Yi Chen Yang, Min Kuang Tsai, Chwen Keng Tsao, Carol Etzel, Maosheng Huang, Chung Yi Hsu, Yuanqing Ye, Lopa Mishra, Ernest Hawk, Xifeng Wu
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundRisk prediction models for hepatocellular carcinoma are available for individuals with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections who are at high risk but not for the general population with average or unknown risk. We developed five simple risk prediction models based on clinically available data from the general population.
Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma
Authors: M J Vaquerizo
Journal: Thorax (2003)

Proinflammatory leukotrienes, which are not completely inhibited by inhaled corticosteroids, may contribute to asthmatic problems [corrected]. A 16 week multicentre, randomised, double blind, controlled study was undertaken to study the efficacy of adding oral montelukast, a leukotriene receptor antagonist, to a constant dose of inhaled budesonide.A total of 639 patients aged 18-70 years with forced expiratory volume in 1 second (FEV(1)) > or =55% predicted and a minimum predefined level of asthma symptoms during a 2 week placebo run in period were randomised to receive montelukast 10 mg (n=326) or placebo (n=313) once daily for 16 weeks. All patients received a constant dose of budesonide (400-1600 microg/day) by Turbuhaler throughout the study.Mean FEV(1) at baseline was 81% predicted. The median percentage of asthma exacerbation days was 35% lower (3.1% v 4.8%; p=0.03) and the median percentage of asthma free days was 56% higher (66.1% v 42.3%; p=0.001) in the montelukast group than in the placebo group. Patients receiving concomitant treatment with montelukast had significantly (p<0.05) fewer nocturnal awakenings and significantly (p<0.05) greater improvements in beta agonist use and morning peak expiratory flow rate (PEFR).For patients with mild airway obstruction and persistent asthma symptoms despite budesonide treatment, concomitant treatment with montelukast significantly improves asthma control.
Surgical Treatment of Gastrooesophageal Reflux in Severely Mentally Retarded Children
Authors: Lewis Spitz
Journal: Journal of the Royal Society of Medicine (1982)

Twenty severely mentally retarded children with significant gastrooesophageal reflux were submitted to surgical treatment. In all patients vomiting was present to a distressing degree in 5 children, 3 of whom required extensive surgery to overcome the obstruction. All had failed to respond to conservative measures. Although the postoperative complication rate was high (50%), the final result in the majority of patients was highly satisfactory.