tbuckley/cabot-search huggingface dataset:
Role of medical thoracoscopy in a developing country: A single unit experience from Sri Lanka
Authors: Dushantha Madegedara, Neranjan Dissanayake, Duminda Yasaratne, Chandana Kulathunga, Samadara Nakandala, Prasanne Wijerathne, Chathura Wirasinghe
Journal: European Respiratory Journal (2011)

Introduction:  Medical thoracoscopy (MT) is proven as an effective tool in managing pleural disease, but is scarcely available in resource poor environments.   Objective:  To describe the utility and safety of MT in managing exudative pleural effusions in the local settieng.   Method:  We descriptively analyzed 96 MTs performed during past year in our unit.   Results:  8 MTs failed due to non-collapsible lung (6) and poor patient compliance (2). Of the 88 where visualisation of pleural cavity was possible,51 had septate fibro-purulent exudate and 20 had non purulent exudate. Haemorrhagic effussion was seen in 15, while 2 had food particles in the cavity.  Inaddition to biopsies taken from parietal pleura, 36 had abnormal pleural nodules out of which 27 were were amenable for biopsy.  In 56, previous diagnostic procedures had failed to arrive at a specific diagnosis.We diagnosed pleural tuberculosis (38), empyema (28), malignant pleural deposits (19), oesophageal rupture (2) and chylothorax (1) in the cohort. During the diagnostic process 7 had to undergo repeat MT. Therapeutic lavage of the pleural cavity was performed where relevant, while 47 underwent adhesiolysis.MT based pleurodesis was not done.  Pain at incision site (62), persistant discharge (12) and infection (3) at entry site were the common complications noted. Post procedure empyema, visceral organ damage or MT related deaths were not encountered.   Conclusion:  With MT, we were able to diagnose many previously delayed pleural diseases of different aetiologies, with minimum post procedure complications. MT served as a safe and effective diagnostic tool in our establishment. Therapeutic use should be enhanced to include MT based pleurodesis.
Abstract 1607: Quantitative membrane proteome profiling to discover therapeutic targets for adult T-cell leukemia (ATL)
Authors: Makoto Ishihara, Natsumi Araya, Tomoo Sato, Risa Fujii, Ayako Tatsuguchi, Naomi Saichi, Hidewaki Nakagawa, Yoshihisa Yamano, Koji Ueda
Journal: Cancer Research (2014)

Abstract Human T-cell leukemia virus type 1 (HTLV-1) is one of retroviruses known as the causative agent of adult T-cell leukemia (ATL), which is infected within 20 million people in the world. ATL develops at the prevalence of only 5% among HTLV-1-infected individuals after a long latency period over 30 years. However, the outcomes of conventional treatment for ATL are not satisfactory, exhibiting overall 5-year survival rate of 20%. To discover novel therapeutic targets for ATL, we performed label-free quantitative membrane proteome analysis for CD4+ T-cell subpopulation in which HTLV-1 infected cells are enriched. Tryptic digests of CD4+ T-cells were prepared from 14 normal donors (ND), 21 asymptomatic carriers (AC), and 13 ATL patients. To focus on the membrane derived peptides, glycosylated peptides were enriched by lectin column chromatography (Mol Cell Proteomics. 2010,9(9),1819) since most of membrane proteins are glycosylated. The eluates were analyzed by LC/MS/MS and 8,658 N-glycosylated peptides derived from 1,134 N-glycosylated proteins were identified. The therapeutic targets were subsequently extracted by a couple of criteria as follows. The all-or-nothing analysis explored peptides detected in none or 1 case of ND+AC group, resulting in identification of 31 peptides derived from 19 proteins. Additionally Welch's t-test (ATL vs. ND+AC) identified 33 peptides derived from 14 proteins (p &amp;lt; 0.05 and fold change &amp;gt; 2.0). The identified therapeutic target molecules above included cell adhesion molecule 1 (CADM1 or TSLC1) which overexpresses in ATL cells and induces organ infiltration of tumor cells. Programmed cell death 1 ligand 1 (PD1L1) was also found in our therapeutic target list, which was known to be up-regulated in ATL cells and involved in induction of immune tolerance. These facts strongly emphasize the credibility of our quantitative profiling results. We would like to show the results of functional inhibitory experiments for novel therapeutic targets and discuss the uncovered molecular mechanisms of ATL progression. Note: This abstract was not presented at the meeting. Citation Format: Makoto Ishihara, Natsumi Araya, Tomoo Sato, Risa Fujii, Ayako Tatsuguchi, Naomi Saichi, Hidewaki Nakagawa, Yoshihisa Yamano, Koji Ueda. Quantitative membrane proteome profiling to discover therapeutic targets for adult T-cell leukemia (ATL). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1607. doi:10.1158/1538-7445.AM2014-1607
High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia
Authors: M. Lafaurie, J. Lapalu, E. Raffoux, B. Breton, C. Lacroix, G. Socié, R. Porcher, P. Ribaud, S. Touratier, J.-M. Molina
Journal: Clinical Microbiology and Infection (2009)
In brief
Authors: F Charatan
Journal: BMJ (2001)

Death rates from lung cancer among white women in the United States increased by 600% between 1950 and 2000, a report from the US surgeon general stated this week. The rate was 5 per 100000 in 1950 and 35 per 100000 in the year 2000.

In 1950 lung cancer accounted for only 3% of all female cancer deaths, whereas in 2000 it accounted for an estimated 25% Twenty seven thousand more women died of lung cancer than of breast cancer in …
The prediction of airway wall thickening by computer aided lung sound analysis
Authors: Surussawadi Mackawan, Anne Bruton, Anna Barney, Michael Bennett, Tom Havelock
Journal: European Respiratory Journal (2012)

Computer Aided Lung Sound Analysis (CALSA) has been used to detect and analyse added lung sounds to aid diagnosis of many respiratory diseases. The wall area of the main bronchi, expressed as a percentage of the cross-sectional area of each branch, is a biomarker of chronic airway inflammation which is raised in COPD. The objective of this study was to explore the possible relationship between characteristics of crackles measured by CALSA and percentage of wall area of the main bronchi measured by High Resolution Computed Tomography (HRCT), and hence the possibility of using crackles as a biomarker of COPD. 26 participants (9 healthy non-smokers, 9 healthy smokers and 8 COPD) were recruited. Lung sound data were recorded using a digital stethoscope. HRCT scans were conducted using a Siemens Sensation 64 CT scanner and the resulting data were analysed using the Pulmonary Workstation 2 (Vida Diagnostics, Iowa, US) software to give measurements of airway geometry. The results showed that the percentage of wall area at the right upper bronchus correlated with the two cycle duration of crackles (r=-0.39, p=0.025) recorded at the right upper lobe (RUL), the number of crackles per breathing cycle (NCpB) at RUL (r=-0.49, p=0.005) and NCpB at right lower lobe (r=-0.49, p=0.006). Additionally, the NCpB at RUL was found to significantly predict the percentage of wall area at the right upper bronchus (adjusted R²=0.20, R²=0.24, p=0.010). These initial results suggest NCpB might be useable to predict changes in percentage of wall area caused by the chronic inflammation of the main bronchi, though a larger sample is needed to confirm it. This suggests that crackles could possibly be used as a biomarker of COPD.
Controlling Tuberculosis in India
Authors: Zarir F Udwadia
Journal: New England Journal of Medicine (2003)

The report by Khatri and Frieden (Oct. 31 issue) on tuberculosis control in India echoes the official line of the Indian government health policy bureaucrats and the World Health Organization. Sadly data collection in India cannot be taken at face value and the accuracy of the impressive cure rates has been questioned. The 200000 new health workers alluded to are but a small fraction of those required to take on the additional burden imposed by direct observation. This shortage constrains the Revised National Tuberculosis Control Program (RNTCP) to recommend direct observation of only 6 of the 18 continuation-phase doses and this incomplete supervision at a time when the illness is improving and the patient is least compliant has been dismissed as only partially observed therapy. (excerpt)
Protein Tyrosine Phosphatase 1B Inhibitors: A Molecular Level Legitimate Approach for the Management of Diabetes Mellitus
Authors: Suresh Thareja, Saurabh Aggarwal, T. R. Bhardwaj, Manoj Kumar
Journal: Medicinal Research Reviews (2010)

Abstract Diabetes mellitus is a systemic disease responsible for morbidity in the western world and is gradually becoming prevalent in developing countries too. The prevalence of diabetes is rapidly increasing in industrialized countries and type 2 diabetes accounts for 90% of the disease. Insulin resistance is a major pathophysiological factor in the development of type 2 diabetes, occurring mainly in muscle, adipose tissues, and liver leading to reduced glucose uptake and utilization and increased glucose production. The prevalence and rising incidence of diabetes emphasized the need to explore new molecular targets and strategies to develop novel antihyperglycemic agents. Protein Tyrosine Phosphatase 1B (PTP 1B) has recently emerged as a promising molecular level legitimate therapeutic target in the effective management of type 2 diabetes. PTP 1B, a cytosolic nonreceptor PTPase, has been implicated as a negative regulator of insulin signal transduction. Therefore, PTP 1B inhibitors would increase insulin sensitivity by blocking the PTP 1B‐mediated negative insulin signaling pathway and might be an attractive target for type 2 diabetes mellitus and obesity. With X‐ray crystallography and NMR‐based fragment screening, the binding interactions of several classes of inhibitors have been elucidated, which could help the design of future PTP 1B inhibitors. The drug discovery research in PTP 1B is a challenging area to work with and many pharmaceutical organizations and academic research laboratories are focusing their research toward the development of potential PTP 1B inhibitors which would prove to be a milestone for the management of diabetes. © 2010 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 459–517, 2012
Immunotherapy with peptides
Authors: D. Moldaver, M. Larché
Journal: Allergy (2011)

To cite this article: Moldaver D, Larché M. Hundred years of allergen-specific immunotherapy. Allergy 2011; 66: 784–791. Specific allergen immunotherapy is clinically effective and disease modifying. It has a duration of effect that exceeds the treatment period and prevents both the progression of allergic rhinitis to asthma and the acquisition of new allergic sensitizations. However, immunotherapy is associated with a high frequency of adverse events related to the allergenicity of vaccines. Allergenicity is conferred by the presence of intact B-cell epitopes that crosslink allergen-specific IgE on effector cells. The use of linear peptide sequences representing fragments of the native allergen is one approach to reduce allergenicity. Preclinical models of peptide immunotherapy have demonstrated efficacy in both autoimmunity and allergy. Translation of this technology into the clinic has gained momentum in recent years based on encouraging results from early clinical trials. To date, efforts have focused on two major allergens, but vaccines to a broader range of molecules are currently in clinical development. Mechanistically, peptide immunotherapy appears to work through the induction of adaptive, allergen-specific regulatory T cells that secrete the immunoregulatory cytokine IL-10. There is also evidence that peptide immunotherapy targeting allergen-specific T cells can indirectly modulate allergen-specific B-cell responses. Peptide immunotherapy may provide a safe and efficacious alternative to conventional subcutaneous and/or sublingual approaches using native allergen preparations.
Characterization of microRNA expression and their biological correlates in the NCI-60 panel of human tumor derived cell lines
Authors: Arti B. Gaur, David A. Jewell, Yu Liang, Dana Ridzon, Jason H. Moore, Caifu Chen, Victor R. Ambros, Mark A. Israel
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4171 

We sought to examine microRNA (miRNA) expression patterns in the NCI-60 panel of human tumor derived cell lines. MiRNAs are small noncoding RNAs that play a critical role in developmental and physiological processes by regulating target gene expression at the post-transcriptional level. Significant evidence suggests that miRNAs are implicated in the pathogenesis of several human diseases including cancer. In some tumors, miRNA expression profiles can be used to distinguish malignant from normal tissue. We examined the expression profiles of 247 human miRNAs in normal tissues and the NCI-60 panel of tumor derived cell lines. We employed a highly sensitive technique that utilizes stem-loop primers for reverse transcription (RT) followed by real-time PCR. This strategy permits us to quantify miRNAs from as little as 25 pg total RNA; the Ct values measure up to four orders of magnitude of copy number. The data we obtained by this approach were examined by hierarchical cluster analysis and the statistical significance of the results were confirmed with multiscale bootstrap re-sampling analyses. We found that most miRNAs were expressed at lower levels in tumor derived cell lines than in the corresponding normal tissue. For tumor cell lines derived from many different tumors we found that specific patterns of miRNA expression could distinguish tumor cell lines from the corresponding normal tissue. Tumor cell lines derived from specific tumor types such as colon cancer and melanoma could be recognized as sharing common patterns of expression of some miRNAs. The miRNA expression pattern we found to be characteristic of the cell lines derived from hematologic tumors was identical to a pattern recently reported by others as resulting from a genomic amplification in large B-cell lymphomas. Furthermore, specific miRNA expression patterns correlated with particular mutations and the proliferative indices of the cell lines we have studied. Our findings indicate that miRNA expression patterns are closely related to definable characteristics of tumor derived cell lines. These patterns may either mark specific biologic characteristics or may mediate specific biologic activities important for the pathobiology of malignant tumors. These studies were supported by grants from the Betz Foundation.
Postprogression survival of patients with advanced hepatocellular carcinoma: Rationale for second-line trial design
Authors: Maria Reig, Jordi Rimola, Ferran Torres, Anna Darnell, Carlos Rodriguez-Lope, Alejandro Forner, Neus LLarch, José Ríos, Carmen Ayuso, Jordi Bruix
Journal: Hepatology (2013)

Sorafenib improves overall survival (OS) of patients with hepatocellular carcinoma (HCC) in the absence of objective response. Thus, time to tumor progression (TTP) is used to capture benefits of novel molecular agents, but proof of its surrogacy with survival is lacking. Furthermore, survival predictors upon progression are not established and there is a need to characterize postprogression survival (PPS) and assess with time-dependent covariates analysis if it is influenced by progression pattern, and not solely by simultaneous impairment of liver function and performance status. We prospectively followed HCC patients treated with sorafenib. Clinical and biochemical evaluation were done every 4 weeks. Radiologic assessment of progression was done at week 4 and then every 8 weeks using RECIST 1.1. The progression pattern was divided into: intrahepatic/extrahepatic increase in tumor size, new intrahepatic lesion, and new extrahepatic lesion (NEH). We included 147 patients (hepatitis C virus [HCV] 57.1%, performance status [PS] 0 83.6%, Child-Pugh A 82.3%, and BCLC-C 47.3%). The median OS was 12.7 months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were: baseline BCLC 2.49 [1.66-3.73], PS 1.86 [1.12-3.10], registration during follow-up of Child-Pugh B or Child-Pugh C scores (2.36 [1.51-3.69] and 2.89 [1.62-5.15], respectively), definitive sorafenib interruption 2.48 [1.54-4.01], and TTP 3.39 [1.89-6.1]. The presence of NEH 2.42 [1.32-4.44] is also an independent predictor of OS and PPS in patients with radiologic progression.Tumor progression is a surrogate of survival but its impact varies according to progression pattern. Thus, PPS is influenced by progression pattern and this is key in prognostic prediction and second-line trial design and analysis.
Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia
Authors: Woo-Joo Song, Melanie G. Sullivan, Robert D. Legare, Sarah Hutchings, Xiaolian Tan, Dubravka Kufrin, Janina Ratajczak, Isabel C. Resende, Catherine Haworth, Randy Hock, Mignon Loh, Carolyn Felix, Denis-Claude Roy, Lambert Busque, David Kurnit, Cheryl Willman, Alan M. Gewirtz, Nancy A. Speck, John H. Bushweller, Frederick P. Li, Katheleen Gardiner, Mortimer Poncz, John M. Maris, D. Gary Gilliland
Journal: Nature Genetics (1999)
Abstract P210: Weight and Body Image Perceptions in Young, Low Income Adult Latinas with Imprecise Body Mass Index Classification
Authors: Jen Rinaldo, Erika Froelicher, Catherine Waters, Kirsten Bibbins-Domingo, Nancy Stotts
Journal: Circulation (2014)

Introduction: Mexican American women in the US have the second highest prevalence of overweight or obesity (78.2%), 44.8% are obese, yet little research has examined the relationship between body mass index (BMI) and body satisfaction among young, low-income Latina adults. Objective: To examine the relationships between knowledge, attitudes, beliefs, and behaviors about weight, body image and excess weight. Hypothesis: We hypothesized that (1) the women would incorrectly classify BMI; (2) the majority would be obese and (3) there is no difference in body satisfaction among those with and without excess weight. Methods: A cross-sectional study with a convenience sample of 131 self-identified Latina women, ages 18 to 45 years was used from two Northern California clinics. An interview administered questionnaire assessed demographics, weight and body image. Statistical analysis included descriptive statistics, chi-square statistics, and logistic regression analysis. Results: While 31% (n=41) classified themselves as having a healthy BMI, 21% (n= 27) met the criteria. Although 58% (n=77) classified themselves as overweight, 46% (n=60) met the criteria. Although 2% (n=3) classified themselves as obese, 34% (n=44) were obese. The majority of women (67%; n=88) reported that they were not at their ideal body weight. Of those who wanted to lose weight, the mean number of pounds they would have to lose to be at their ideal body weight was 15.5 (± 16). The mean body dissatisfaction score of those with excess weight was 2.2 (± 1.1) and 0.74 (± 1.4) for those with healthy BMI. Conclusions: Most women underestimated their BMI category. Less than 6% (n=3) of obese women correctly classified themselves as obese. The misclassification and underreporting of excess weight was statistically significant (p≤ 0.05), pointing to a need for education about weight. Body dissatisfaction scores were higher in women with excess weight. Actual/current body silhouette sizes were statistically significantly associated with excess weight: (OR=2.78, 95% CI: 1.28, 6.04, p= 0.02).
Global DNA methylation and hydroxymethylation differ in hepatocellular carcinoma and cholangiocarcinoma and relate to survival rate
Authors: Silvia Udali, Patrizia Guarini, Sara Moruzzi, Andrea Ruzzenente, Stephanie A. Tammen, Alfredo Guglielmi, Simone Conci, Patrizia Pattini, Oliviero Olivieri, Roberto Corrocher, Sang‐Woon Choi, Simonetta Friso
Journal: Hepatology (2015)

In addition to DNA methylation, hydroxymethylation of DNA is recognized as a novel epigenetic mark. Primary liver cancers, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), are highly prevalent but epigenetically poorly characterized, so far. In the present study we measured global methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) in HCC and CC tissues and in peripheral blood mononuclear cell (PBMC) DNA to define mCyt and hmCyt status and, accordingly, the survival rate. Both mCyt and hmCyt were measured by a liquid chromatography/tandem mass spectrometry method in neoplastic and homologous nonneoplastic tissues, i.e., liver and gallbladder, and in PBMCs of 31 HCC and 16 CC patients. Content of mCyt was notably lower in HCC than in CC tissues (3.97% versus 5.26%, respectively; P &lt; 0.0001). Significantly reduced mCyt was also detected in HCC compared to nonneoplastic tissue (3.97% versus 4.82% mCyt, respectively; P &lt; 0.0001), but no such difference was found for CC versus homologous nonneoplastic tissue. Hydroxymethylation was significantly decreased in HCC versus nonneoplastic liver tissue (0.044 versus 0.128, respectively; P &lt; 0.0001) and in CC versus both liver and gallbladder nonneoplastic tissue (0.030 versus 0.124, P = 0.026, and 0.030 versus 0.123, P = 0.006, respectively). When the survival rate was evaluated according to mCyt PBMC content by Kaplan‐Meier analysis, patients with mCyt ≥5.59% had a significantly higher life expectancy than those with mCyt &lt;5.59% ( P = 0.034) at a follow‐up period up to 48 months. Conclusion : A significant DNA hypomethylation distinguishes HCC from CC, while DNA hypo‐hydroxymethylation characterizes both HCC and CC, and a PBMC DNA mCyt content ≥5.59% relates to a favorable outcome in primary liver cancers. (H epatology 2015;62:496–504