tbuckley/cabot-search huggingface dataset:
Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma
Authors: I Tischoff, U R Hengge, M Vieth, C Ell, M Stolte, A Weber, W E Schmidt, A Tannapfel
Journal: Gut (2007)

The suppressors of cytokine signalling (SOCS) are inhibitors of cytokine signalling; methylation of SOCS-3 has been implicated in the tumorigenesis of liver as well as head and neck cancer.This study was performed to elucidate the role of SOCS-1 and SOCS-3 in Barrett's adenocarcinoma and its precursor lesions.DNA of specimens from 19 Barrett's adenocarcinomas, 56 Barrett's intraepithelial neoplasias (n = 29 low grade and n = 27 high grade), 30 Barrett's mucosa without neoplasia, 20 samples of normal squamous and gastric epithelium and four cell lines were studied using methylation specific PCR for the SOCS-1 and SOCS-3 promoter following microdissection. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real time PCR, and the SOCS-3 protein was analysed immunohistochemically.In normal squamous epithelium and normal gastric mucosa, neither SOCS-3 nor SOCS-1 methylation was observed. In Barrett's mucosa without intraepithelial neoplasia, SOCS-3 methylation occurred in 4/30 cases (13%) whereas SOCS-1 was unmethylated. A hypermethylated SOCS-3 promoter was found in 14/19 Barrett's adenocarcinomas (74%) and in 20/29 high and 6/27 low grade intraepithelial neoplasias (69% and 22%, respectively). SOCS-1 promoter hypermethylation occurred in 8/19 adenocarcinomas (42%) and in 6/29 high grade and 1/27 low grade intraepithelial neoplasias (21% and 4%, respectively). Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumours and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased after treatment with the demethylation compound 5-aza-2-deoxycytidine.These data indicate that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of Barrett's adenocarcinoma.
High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Ovarian Cancer: An Autologous Blood and Marrow Transplant Registry Report
Authors: Patrick J. Stiff
Journal: Annals of Internal Medicine (2000)

Background: Autologous transplantation is increasingly used to treat epithelial ovarian cancer. However, it is not clear which patients may benefit. Objective: To determine overall and progression-free survival and factors associated with favorable outcome after autotransplantation for ovarian cancer. Design: Observational cohort study. Setting: 57 centers reporting to the Autologous Blood and Marrow Transplant Registry (ABMTR). Patients: 421 women who received transplants between 1989 and 1996. Interventions: High-dose chemotherapy using diverse regimens with hematopoietic stem-cell rescue. Measurements: Primary outcomes were progression-free survival and overall survival. Multivariate analyses using Cox proportional-hazards regression considered the following factors: age, Karnofsky performance score, initial stage, histologic characteristics, previous therapy, remission status, extent of disease, graft source, transplant regimen, and year of transplantation. Results: Most patients had extensive previous chemotherapy. Forty-one percent had platinum-resistant tumors, and 38% had tumors at least 1 cm in diameter. Only 34 patients (8%) received transplants as part of initial therapy. The probability of death within 100 days was 11% (95% CI, 8% to 14%). Two-year progression-free survival was 12% (CI, 9% to 16%), and 2-year overall survival was 35% (CI, 30% to 41%). Younger age, Karnofsky performance score of at least 90%, non–clear-cell disease, remission at transplantation, and platinum sensitivity were associated with better outcomes. Progression-free and overall survival were 22% (CI, 12% to 33%) and 55% (CI, 42% to 66%), respectively, for women with a high Karnofsky performance score and non–clear-cell, platinum-sensitive tumors. Conclusions: Some subgroups of patients with ovarian cancer seem to have good outcomes after autotransplantation, although several biases may have affected these observations. Phase III trials are needed to compare such outcomes with outcomes of conventional chemotherapy.
miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response
Authors: Bogdan Mateescu, Luciana Batista, Melissa Cardon, Tina Gruosso, Yvan de Feraudy, Odette Mariani, André Nicolas, Jean-Philippe Meyniel, Paul Cottu, Xavier Sastre-Garau, Fatima Mechta-Grigoriou
Journal: Nature Medicine (2011)
Soluble intercellular adhesion molecule-1 (s-ICAM-1/s-CD54) in diffuse large B-cell lymphoma: association with clinical characteristics and outcome
Authors: M.J. Terol, M. Tormo, J.A. Martinez-Climent, I. Marugan, I. Benet, A. Ferrandez, A. Teruel, R. Ferrer, J. García-Conde
Journal: Annals of Oncology (2003)
Pleural fluid chemical analysis in parapneumonic effusions. A meta-analysis.
Authors: J E Heffner, L K Brown, C Barbieri, J M DeLeo
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Controversy exists regarding the clinical utility of pleural fluid pH, lactate dehydrogenase (LDH), and glucose for identifying complicated parapneumonic effusions that require drainage. In this report, we performed a meta-analysis of pertinent studies, using receiver operating characteristic (ROC) techniques, to assess the diagnostic accuracy of these tests, to determine appropriate decision thresholds, and to evaluate the quality of the primary studies. Seven primary studies reporting values for pleural fluid pH (n = 251), LDH (n = 114), or glucose (n = 135) in pneumonia patients were identified. We found that pleural fluid pH had the highest diagnostic accuracy for all patients with parapneumonic effusions as measured by the area under the ROC curve (AUC = 0.92) compared with pleural fluid glucose (AUC = 0.84) or LDH (AUC = 0.82). After excluding patients with purulent effusions, pH (AUC = 0.89) retained the highest diagnostic accuracy. Pleural fluid pH decision thresholds varied between 7.21 and 7.29 depending on cost-prevalence considerations. The quality of the primary studies was the major limitation in determining the value of pleural fluid chemical analysis. We conclude that meta-analysis of the available data refines the application of pleural fluid chemical analysis but a clearer understanding of the usefulness of these tests awaits more rigorous primary investigations.
Long-Term Budesonide Maintenance Treatment Is Partially Effective for Patients With Eosinophilic Esophagitis
Authors: Alex Straumann, Sebastien Conus, Lukas Degen, Cornelia Frei, Christian Bussmann, Christoph Beglinger, Alain Schoepfer, Hans–Uwe Simon
Journal: Clinical Gastroenterology and Hepatology (2011)
Vitamin D Beyond Bones in Chronic Obstructive Pulmonary Disease
Authors: Wim Janssens, An Lehouck, Claudia Carremans, Roger Bouillon, Chantal Mathieu, Marc Decramer
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The discovery that the vitamin D endocrine system regulates a very large number of genes and their associated biological processes improves our insight into the fundamental role of vitamin D and sun exposure for human health. Accumulating epidemiological data are linking a low vitamin D nutritional status to highly prevalent diseases such as cancer, autoimmune diseases, and chronic infections. Approximately half of the world's elderly, and to a lesser extent the adult population, have insufficient to deficient 25-hydroxyvitamin D (25-OHD) serum levels, and several intervention studies are being undertaken to study the impact of adequate vitamin D supplementation in chronic diseases. In this perspective we claim that chronic obstructive pulmonary disease (COPD) is a candidate disease for which vitamin D supplementation might be beneficial. Epidemiological studies revealed a dose-dependent association between serum 25-OHD levels and pulmonary function so that adequate vitamin D supplementation may extend beyond its protection against osteoporotic fractures. In line with the novel insights on its immune function, it is tempting to speculate that vitamin D may down-regulate the inflammatory immune response in the airways while boosting innate immune defense against different microorganisms. Apart from its affects on osteoporosis, vitamin D may also interfere with other comorbidities of COPD such as skeletal muscle weakness, cardiovascular disease, and cancer. Because respiratory treatments in COPD fail to reverse disease progression, interventional trials that may exploit the broader potential of vitamin D are warranted. A further challenge of such studies is to define optimal serum 25-OHD levels for such noncalcemic endpoints.
Regulation of B Cell Development by Variable Gene Complexity in Mice Reconstituted with Human Immunoglobulin Yeast Artificial Chromosomes
Authors: Larry L. Green, Aya Jakobovits
Journal: The Journal of Experimental Medicine (1998)

The relationship between variable (V) gene complexity and the efficiency of B cell development was studied in strains of mice deficient in mouse antibody production and engineered with yeast artificial chromosomes (YACs) containing different sized fragments of the human heavy (H) chain and kappa light (L) chain loci. Each of the two H and the two kappa chain fragments encompasses, in germline configuration, the same core variable and constant regions but contains different numbers of unique VH (5 versus 66) or Vkappa genes (3 versus 32). Although each of these YACs was able to substitute for its respective inactivated murine counterpart to induce B cell development and to support production of human immunoglobulins (Igs), major differences in the efficiency of B cell development were detected. Whereas the YACs with great V gene complexity restored efficient development throughout all the different recombination and expression stages, the YACs with limited V gene repertoire exhibited inefficient differentiation with significant blocks at critical stages of B cell development in the bone marrow and peripheral lymphoid tissues. Our analysis identified four key checkpoints regulated by VH and Vkappa gene complexity: (a) production of functional mu chains at the transition from the pre B-I to the pre B-II stage; (b) productive VkappaJkappa recombination at the small pre B-II stage; (c) formation of surface Ig molecules through pairing of mu chains with L chains; and (d) maturation of B cells. These findings demonstrate that V gene complexity is essential not only for production of a diverse repertoire of antigen-specific antibodies but also for efficient development of the B cell lineage.
INTEGRATIVE BIOLOGY OF PROSTATE CANCER PROGRESSION
Authors: Scott A. Tomlins, Mark A. Rubin, Arul M. Chinnaiyan
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Prostate cancer displays considerable clinical, morphological, and biological heterogeneity. Classical genetic techniques have provided only limited information about the pathogenesis of prostate cancer progression. Nevertheless, several candidate genes and pathways have been implicated in prostate cancer development. High-throughput techniques have exponentially expanded the number of candidate genes, including some whose role in prostate cancer pathogenesis has been studied. However, the techniques used to study the prostate cancer genome, transcriptome, and proteome generate massive amounts of data that have yet to be integrated and explored. To move beyond candidate gene identification and develop a comprehensive understanding of cancer pathogenesis, integrative approaches need to analyze this data on a global level. This review addresses candidate genes involved in prostate cancer pathogenesis in a biological and clinical context and demonstrates how integrated analysis of high-throughput data augments our understanding of prostate cancer.
Activated protein C resistance caused by factor V Arg 506--&gt;Gln mutation has no role in thrombotic manifestations of Behcet's disease.
Authors: P Lesprit, B Wechsler, J C Piette, L T Du-Boutin, P Godeau, M Alhenc-Gelas, M Aiach
Journal: Annals of the Rheumatic Diseases (1995)

Browne et al, cited by Dr Quintner was an essay in which the authors expressed their views.'2No patient numbers were reported.Dr Quintner may consider my emphasis on the importance of the clinical examination a 'truism', but it is nevertheless one that bears repeating if only to avoid the temptation to rationalise the absence of clinical abnormalities by resorting to untenable hypotheses of neuropathic pain to explain this phenomenon.One can only be grateful that all of that neuropathic pain which afflicted so many Australian workers up until the mid 1980s has seen fit to resolve, apparently spontaneously.
Relative Importance of Borderline and Elevated Levels of Coronary Heart Disease Risk Factors
Authors: Ramachandran S. Vasan, Lisa M. Sullivan, Peter W.F. Wilson, Christopher T. Sempos, Johan Sundström, William B. Kannel, Daniel Levy, Ralph B. D'Agostino
Journal: Annals of Internal Medicine (2005)

Clinical trials indicate that a sizable proportion of adults have multiple borderline coronary risk factors and may benefit from treatment.To estimate the relative and absolute contributions of borderline and elevated risk factors to the population burden of coronary heart disease (CHD) events.A prospective cohort study and a national cross-sectional survey.The Framingham Study and the Third National Health and Nutrition Examination Survey (NHANES III).White non-Hispanic persons in the Framingham Study and in NHANES III who were between 35 to 74 years of age and had no CHD.Occurrence of first CHD events according to 5 major CHD risk factors: blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, glucose intolerance, and smoking. Three categories-optimal, borderline, and elevated-were defined for each risk factor per national guidelines. Sex-specific 10-year CHD event rates from the Framingham Study were applied to numbers of at-risk individuals estimated from NHANES III and the 2000 U.S. Census.Twenty-six percent of men and 41% of women had at least 1 borderline risk factor in NHANES III. According to estimates, more than 90% of CHD events will occur in individuals with at least 1 elevated risk factor, and approximately 8% will occur in people with only borderline levels of multiple risk factors. Absolute 10-year CHD risk exceeded 10% in men older than age 45 years who had 1 elevated risk factor and 4 or more borderline risk factors and in those who had at least 2 elevated risk factors. In women, absolute CHD risk exceeded 10% only in those older than age 55 years who had at least 3 elevated risk factors.The generalizability of the findings to persons of other ethnic backgrounds is unknown.Borderline CHD risk factors alone account for a small proportion of CHD events.
Characteristics of robotically harvested hair follicles in Koreans
Authors: Jung Won Shin, Soon Hyo Kwon, Sung Ae Kim, Joo Yong Kim, Jung Im Na, Kyoung Chan Park, Chang Hun Huh
Journal: Journal of the American Academy of Dermatology (2014)

Recently, an automated robotic hair restoration device was developed and is increasingly being used for hair restoration.We sought to analyze the hair follicles of Korean patients that were harvested by a hair restoration robotic device.Data were reviewed from a total of 22 patients who underwent robotic follicular unit (FU) extraction hair restoration surgery at Seoul National University Bundang Hospital. Hair follicles collected from 3 grids in the central parts of the safe donor zone of each patient were analyzed.The total number of harvested FUs was 5213, and the total number of collected FUs was 4955. The average yield was 95.1% ± 3.5%. Among the 12,017 harvested hairs, 590 hairs were transected and the average transection rate was 4.91% ± 2.9%. FUs of double hairs made up the majority of harvested FUs (44.1%), followed by triple hairs (31.9%). The transection rate increases in FUs that contain multiple hairs.A relatively small sample size and lack of comparative study with conventional FU extraction modalities are limitations.The robotic system qualifies for use in hair restoration surgery. It efficiently harvests not only single hairs but multiple hairs as well.
Interventions in chronic renal failure.
Authors: J R Curtis
Journal: BMJ (1990)

doctors may have had more claims because they took on more difficult cases.Debate will continue on whether a small group of incompetent doctors produce much of the malpractice problem, but the Office of Technology Assessment has suggested that malpractice information should be collected and used for quality screening by hospitals, licensing boards, and others (perhaps even patients).6Indeed, a national database of doctors who have lost malpractice suits went into operation on 1 September (22 September, p 569): hospitals are required to check the database before hiring doctors, but the data are not yet available to patients.The Florida researchers argue that this would be premature, but research in the epidemiology of malpractice must continue so that we have data on which to base such proposals.
Acne conglobata and Klinefelter's syndrome
Authors: A. WOLLENBERG, H. WOLFF, T. JANSEN, M.H. SCHMID, M. RÖCKEN, G. PLEWIG
Journal: British Journal of Dermatology (1997)

Acne conglobata has been reported to be more common and more severe in XYY chromosomal aberration than in normal subjects. Whereas only exceptional cases have been observed in the more common XXY Klinefelter karyotype. We report a 17-year-old male with both Klinefelter's syndrome and acne conglobata, spreading from face to upper arms, trunk, buttocks and upper legs. The serum level of testosterone was normal, whereas luteinizing hormone and follicle-stimulating hormone were elevated. Skin lesions responded well to a combined therapeutic regimen including oral isotretinoin and prednisolone. An overview of severe acne in relation to chromosomal abnormalities is given and diagnostic and therapeutic options discussed.
Dr Runge: a German pioneer in sclerosing therapy in epicondylitis in 1873
Authors: Karsten Knobloch, Andreas Gohritz
Journal: British Journal of Sports Medicine (2010)

<h3>Background</h3> Chimeric antigen receptor (CAR) T cells have been successfully used in tumor immunotherapy due to their strong antitumor responses, especially in hematological malignancies such as B cell acute lymphoid leukemia. However, on-target off-tumor toxicity and poor persistence severely limit the clinical application of CAR-T cell therapy. <h3>Methods</h3> T-cell immunoglobulin mucin domain molecule 3 (TIM-3) was used to develop a second-generation 41BB CD19 CAR linked with a T3/28 chimera, in which truncated extracellular TIM-3 was fused with the CD28 transmembrane and cytoplasmic domains. The efficacy of T3/28 CAR-T cells was evaluated in vitro and in vivo. <h3>Results</h3> We demonstrated that the switch receptor T3/28 preserved the T<sub>CM</sub> phenotype, improved proliferative capacity, and reduced exhaustion of CAR-T cells, resulting in superior in vitro and in vivo antitumor activity in B lymphoma. Importantly, the switch receptor T3/28 substantially prolonged the persistence of CAR-T cells, and the interleukin-21/Stat3 axis probably contributed to the enhanced cytotoxicity of T3/28 CAR-T cells. <h3>Conclusion</h3> Overall, the T3/28 chimera significantly prolonged the persistence of CAR-T cells, and T3/28 CAR-T cells possessed potent antitumor activity in mice, shedding new light on potential improvements in adoptive T cell therapies.
BCG vaccination: 90 years on and still so much to learn ...
Authors: A. Lalvani, S. Sridhar
Journal: Thorax (2010)

Thirdly, and perhaps most importantly, the telemedicine components that would be most crucial to improving adherence need to be better understood, so that the most efficient system can be designed.The current study used self-reported information and was focused on motivating patients to use CPAP.However, current technology can monitor CPAP pressures, leaks and objective compliance and send this information to the practitioner on a daily basis.Could early intervention using this information improve CPAP adherence even more?Alternatively, is it the regular automated telephone followups that are most important in motivating patients to use the device?Does the patient perception of being continuously monitored by their healthcare team (whether or not they actually are) serve as the main motivator for adherence?Despite these caveats, we believe it likely that telemedicine will be integrated into the care of patients with OSA in the near future.The potential benefits in terms of monitoring, early intervention of problems, patient education, improving adherence and improving patient outcomes should outweigh technology costs.However, the most cost-efficient way to do this is yet to be determined.
Stichoposide C Induces Apoptosis through the Generation of Ceramide in Leukemia and Colorectal Cancer Cells and Shows <i>In Vivo</i> Antitumor Activity
Authors: Seong-Hoon Yun, Eun-Seon Park, Sung-Won Shin, Yong-Woo Na, Jin-Yeong Han, Jin-Sook Jeong, Valeria V. Shastina, Valentin A. Stonik, Joo-In Park, Jong-Young Kwak
Journal: Clinical Cancer Research (2012)

Marine triterpene glycosides that are physiologically active natural compounds isolated from sea cucumbers (holothurians) and sponges have antifungal, cytotoxic, and antitumor activities, whose specific molecular mechanisms remain to be elucidated. In this study, we examined if and through which mechanisms stichoposide C (STC) from Thelenota anax (family Stichopodidae) induces apoptosis in leukemia and colorectal cancer cells.We examined STC-induced apoptosis in human leukemia and colorectal cancer cells in the context of mitochondrial injury and signaling pathway disturbances, and investigated the antitumor effect of STC in mouse CT-26 subcutaneous tumor and HL-60 leukemia xenograft models.We found that STC induces apoptosis in these cells in a dose-dependent manner and leads to the activation of Fas and caspase-8, cleavage of Bid, mitochondrial damage, and activation of caspase-3. STC activates acid sphingomyelinase (SMase) and neutral SMase, which resulted in the generation of ceramide. Specific inhibition of acid SMase or neutral SMase and siRNA knockdown experiments partially blocked STC-induced apoptosis. Moreover, STC markedly reduced tumor growth of HL-60 xenograft and CT-26 subcutaneous tumors and increased ceramide generation in vivo.Ceramide generation by STC, through activation of acid and neutral SMase, may in part contribute to STC-induced apoptosis and antitumor activity. Thus, STC may have therapeutic relevance for human leukemia and colorectal cancer.
Effects of PEEP on respiratory mechanics in patients with COPD on mechanical ventilation
Authors: B van den Berg, H Stam, JM Bogaard
Journal: European Respiratory Journal (1991)

We studied the effects of positive end-expiratory pressure (PEEP) applied by the ventilator on respiratory mechanics in ventilated patients with chronic obstructive pulmonary disease (COPD). Airway pressures, relaxed expiratory flow-volume curves and end-expiratory volumes (EEV) were measured. In all patients investigated without PEEP applied by the ventilator, an intrinsic PEEP level (PEEPi) and a concavity in the flow-volume curve was present. Ventilator-PEEP caused a significant decrease in PEEPi in all patients (p less than 0.01). In patients in whom ventilator-PEEP exceeded PEEPi, significant increases occurred in airway pressures and EEV (p less than 0.05) and moreover the shape of the flow-volume curve was changing. In patients in whom the level of ventilator-PEEP was below the PEEPi level, no significant changes in airway pressures, EEV or flow-volume curves were found. We conclude: 1) PEEP applied by the ventilator can reduce PEEPi in ventilated patients with COPD without significant changes in airway pressures, EEV or flow-volume curves. 2) Expiratory flow-volume curves can be used to estimate the effects of ventilator-PEEP on EEV.