tbuckley/cabot-search huggingface dataset:
Bone fractures after menopause
Authors: P. G. Crosignani
Journal: Human Reproduction Update (2010)

Every year 30% of individuals above age 65 fall, and falls are the principal cause of bone fractures. To reduce fracture incidence requires both prevention of falls and maintenance of bone strength. PubMed searches were performed, for studies of the epidemiology of fractures, bone physiology, endocrine effects, osteoporosis measurement, genetics, prevention and effectiveness. Topic summaries were presented to the Workshop Group and omissions or disagreements were resolved by discussion. Ageing reduces bone strength in post-menopausal women because estrogen deficiency causes accelerated bone resorption. Bone mineral density (BMD) decreased more than 2.5 standard deviation below the mean of healthy young adults defines osteoporosis, a condition associated with an increased risk of fractures. Risk factors such as age and previous fracture are combined with BMD for a more accurate prediction of fracture risk. The most widely used assessment tool is FRAX™ which combines clinical risk factors and femoral neck BMD. General preventive measures include physical exercise to reduce the risk of falling and vitamin D to facilitate calcium absorption. Pharmacological interventions consist mainly in the administration of inhibitors of bone resorption. Randomized controlled trials show treatment improves BMD, and may reduce the relative fracture risk by about 50% for vertebral, 20–25% for non-vertebral and up to 40% for hip fractures although the absolute risk reductions are much lower. Although diagnosis of osteoporosis is an important step, the threshold for treatment to prevent fractures depends on additional clinical risk factors. None of the presently available treatment options provide complete fracture prevention.
S32 Pepsin detection in expectorated saliva: a useful marker for airway reflux?: Abstract S32 Table 1.
Authors: S Faruqi, AD Woodcock, PW Dettmar, AH Morice
Journal: Thorax (2013)

<h3>Introduction</h3> Gastro oesophageal reflux (GOR) is a very common cause for chronic cough. The clinical history of airway reflux differs from that of GOR disease and often the diagnosis of airways reflux is not considered. Although oesophageal investigations can support the diagnosis these are invasive, time consuming and expensive. The presence of pepsin in the oesophagus, or more proximally in the pharynx or the airways, suggest GOR. The aim of this study was to study the diagnostic utility of measuring pepsin in expectorated saliva in unselected patients presenting with chronic cough. <h3>Methods</h3> Consecutive patients referred to the Hull Cough Clinic were instructed to collect expectorated saliva on three occasions following symptoms (paroxysm of cough). Saliva was collected into tubes containing 0.5 ml of 0.01 M citric acid and analysed for the presence of pepsin using a lateral flow test comprising two unique human monoclonal antibodies to pepsin (Peptest™, RDBiomed Ltd). The cut off value to determine pepsin positivity was 25 ng/ml. Patients also completed the Hull Airways Reflux Questionnaire (HARQ), a validated tool to diagnose airways reflux. <h3>Results</h3> 72 patients were included in this study (females 49, mean age 58.3 years). Salivary pepsin assay was positive in at least one sample in 46 (64%). 24, 10 and 12 patients had 1, 2 and 3 positive tests respectively. 10 samples had pepsin levels above 250 ng/ml. For purpose of comparison this data was examined against 300 similar pepsin assays from 100 healthy subjects with no typical or atypical reflux symptoms. In this group only 6 of 300 samples had more than 250 ng/ml of pepsin measured and 64% had all three samples negative for pepsin.<sup>1</sup> This is shown in table 1. The median HARQ score was 30 (range 1–67). <h3>Conclusion</h3> A high proportion of patients with chronic cough have demonstrable levels of pepsin in expectorated saliva at the time of having symptoms. This non invasive test may be a useful investigation to support the diagnosis of airway reflux. <h3>References</h3> Hayat JO <i>et al</i>. Is pepsin detected in the saliva of healthy individuals? <i>Gut</i> 2013: 62 (Suppl 1) A108–A109.
Heparanase promotes the spontaneous metastasis of myeloma cells to bone
Authors: Yang Yang, Veronica MacLeod, Manali Bendre, Yan Huang, Allison M. Theus, Hua-Quan Miao, Paul Kussie, Shmuel Yaccoby, Joshua Epstein, Larry J. Suva, Thomas Kelly, Ralph D. Sanderson
Journal: Blood (2004)
PHIDIAS: a pathogen-host interaction data integration and analysis system
Authors: Zuoshuang Xiang, Yuying Tian, Yongqun He
Journal: Genome biology (2007)

Abstract The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated from peer-reviewed literature. PHIDIAS is publicly available at http://www.phidias.us .
Activity of the Novel Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235 against T-Cell Acute Lymphoblastic Leukemia
Authors: Francesca Chiarini, Cecilia Grimaldi, Francesca Ricci, Pier Luigi Tazzari, Camilla Evangelisti, Andrea Ognibene, Michela Battistelli, Elisabetta Falcieri, Fraia Melchionda, Andrea Pession, Pasqualepaolo Pagliaro, James A. McCubrey, Alberto M. Martelli
Journal: Cancer Research (2010)

Recent findings have highlighted that constitutively active phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), where it upregulates cell proliferation, survival, and drug resistance. These observations lend compelling weight to the application of PI3K/Akt/mTOR inhibitors in the therapy of T-ALL. Here, we have analyzed the therapeutic potential of the novel dual PI3K/mTOR inhibitor NVP-BEZ235, an orally bioavailable imidazoquinoline derivative, which has entered clinical trials for solid tumors, on both T-ALL cell lines and patient samples. NVP-BEZ235 was cytotoxic to a panel of T-ALL cell lines as determined by MTT assays. NVP-BEZ235 treatment resulted in cell cycle arrest and apoptosis. Western blots showed a dose- and time-dependent dephosphorylation of Akt and mTORC1 downstream targets in response to NVP-BEZ235. Remarkably, NVP-BEZ235 targeted the side population of both T-ALL cell lines and patient lymphoblasts, which might correspond to leukemia-initiating cells, and synergized with chemotherapeutic agents (cyclophosphamide, cytarabine, dexamethasone) currently used for treating T-ALL patients. NVP-BEZ235 reduced chemoresistance to vincristine induced in Jurkat cells by coculturing with MS-5 stromal cells, which mimic the bone marrow microenvironment. NVP-BEZ235 was cytotoxic to T-ALL patient lymphoblasts displaying pathway activation, where the drug dephosphorylated eukaryotic initiation factor 4E-binding protein 1, at variance with rapamycin. Taken together, our findings indicate that longitudinal inhibition at two nodes of the PI3K/Akt/mTOR network with NVP-BEZ235, either alone or in combination with chemotherapeutic drugs, may be an efficient treatment of those T-ALLs that have aberrant upregulation of this signaling pathway for their proliferation and survival.
Geographical mapping of a multifocal thyroid tumour using genetic alteration analysis &amp; miRNA profiling
Authors: Sinéad T Aherne, Paul C Smyth, Richard J Flavin, Susan M Russell, Karen M Denning, Jing Huan Li, Simone M Guenther, John J O'Leary, Orla M Sheils
Journal: Molecular Cancer (2008)

Abstract Background Papillary thyroid carcinoma (PTC) frequently presents as multiple tumour-foci within a single thyroid gland or pluriform, with synchronous tumours comprising different histological variants, raising questions regarding its clonality. Among the genetic aberrations described in PTC, the BRAF V600E mutation and ret/PTC activation occur most commonly. Several studies have investigated the genetic alteration status of multifocal thyroid tumours, with discordant results. To address the question of clonality this study examined disparate geographical and morphological areas from a single PTC (classic PTC, insular and anaplastic foci, and tumour cells adjacent to vascular invasion and lymphocytic infiltrate) for the presence of ret/PTC 1 or BRAF mutations. Moreover, we wanted to investigate the consistency of miRNA signatures within disparate areas of a tumour, and geographical data was further correlated with expression profiles of 330 different miRNAs. Putative miRNA gene targets were predicted for differentially regulated miRNAs and immunohistochemistry was performed on tissue sections in an effort to investigate phenotypic variations in microvascular density (MVD), and cytokeratin and p53 protein expression levels. Results All of the morphological areas proved negative for ret/PTC 1 rearrangement. Two distinct foci with classic morphology harboured the BRAF mutation. All other regions, including the insular and anaplastic areas were negative for the mutation. MiRNA profiles were found to distinguish tumours containing the BRAF mutation from the other tumour types, and to differentiate between the more aggressive insular &amp; anaplastic tumours, and the classic variant. Our data corroborated miRNAs previously discovered in this carcinoma, and additional miRNAs linked to various processes involved in tumour growth and proliferation. Conclusion The initial genetic alteration analysis indicated that pluriform PTC did not necessarily evolve from classic PTC progenitor foci. Analysis of miRNA profiles however provided an interesting variation on the clonality question. While hierarchical clustering analysis of miRNA expression supported the hypothesis that discrete areas did not evolve from clonal expansion of tumour cells, it did not exclude the possibility of independent mutational events suggesting both phenomena might occur simultaneously within a tumour to enhance cancer progression in geographical micro-environments within a tumour.
Extra-hepatic portal vein obstruction (EHPVO) in adult patients: Role of congenital or acquired thrombophylic disorders as etiologic factors
Authors: M. Primignani, N. De Bortoli, M. Moia, P. Bucciarelli, P. Preatoni, P. Carnevale, R. de Franchis
Journal: Journal of Hepatology (2000)
Inflammatory cells as well as epithelial cells in nasal polyps express vascular endothelial growth factor
Authors: A. Coste, L. Brugel, B. Maître, S. Boussat, J.F. Papon, L. Wingerstmann, R. Peynègre, E. Escudier
Journal: European Respiratory Journal (2000)

In nasal polyps (NPs), locally secreted growth factors are involved in the remodelling of the epithelium and extracellular matrix but little is known concerning vessel remodelling. The in situ expression of vascular endothelial growth factor (VEGF) in NPs and control nasal mucosa (CM) were evaluated and in vitro secretion of VEGF from primary human cultures of nasal epithelial cells (HNECs) was quantified. VEGF expression was evaluated in NP (n=14) and CM (n=6) after immunolabelling. In supernatants from HNECs cultured at air/liquid interface, VEGF was quantified by immunoassay, under baseline conditions and after transforming growth factor-beta1 (TGF-beta1) stimulation. In HNEC lysates, VEGF and VEGF messenger ribonucleic acid (mRNA) were detected using Western blot analysis and reverse transcriptase polymerase chain reaction respectively. VEGF positivity was more frequent in inflammatory cells in NPs (14 of 14) than in CM (three of six) (p&lt;0.05) and in the epithelium in NPs (six of 14) than in CM (two of six) (nonsignificant). Under baseline conditions, the VEGF concentration in HNEC culture medium increased from day 2 to 4, then decreased and became undetectable. VEGF concentrations increased significantly after TGF-beta1 stimulation. In HNEC lysates, VEGF and VEGF mRNA were detected on days 4 and 14 of culture. It was concluded that vascular endothelial growth factor is intensely expressed in situ in nasal polyps, mainly in inflammatory cells but also in epithelial cells. Human nasal epithelial cells are able to secrete in vitro vascular endothelial growth factor. Transforming growth factor-beta1 upregulates this secretion. This suggests that vascular endothelial growth factor, inducing oedema and angiogenesis, could be involved in the pathogenesis of nasal polyps.
Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease
Authors: E. Osika, J-M. Cavaillon, K. Chadelat, M. Boule, C. Fitting, G. Tournier, A. Clement
Journal: European Respiratory Journal (1999)

The dominant role of inflammation in airways disease progression in cystic fibrosis (CF) is now well established and, based on recent findings, the possibility of an inappropriate inflammatory response in the lung of patients with CF has emerged. In order to characterize this response, the aim of the present work was to evaluate the levels of a number of pro- and anti-inflammatory cytokines in the sputum of CF children and to compare these levels to those observed in the sputum from non-CF children with diffuse bronchiectasis (DB). Three groups of patients were investigated: a group of 25 CF children (mean age: 12.2 yrs), a group of 10 non-CF children with DB (mean age 11.5 yrs), and a group of five healthy young adults (mean age 24 yrs). Elevated concentrations of pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were found in children with CF and in non-CF children with DB, with significantly higher concentrations of IL-1beta in CF children. Analysis of the natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) and type II TNF soluble receptor (sTNFRII) concentrations showed distinct patterns, with elevated levels of both inhibitors in CF patients, whereas only sTNFRII was found to be increased in non-CF children with DB. IL-10 data indicated low concentrations in the CF group. In all CF children, the concentrations of IL-6 in the airways were extremely low, independent of the clinical, bacteriological or functional status. By contrast, significantly increased IL-6 levels were found in non-CF children with DB. These results document distinct cytokine profiles in cystic fibrosis patients and noncystic fibrosis patients. They also suggest that impairment of interleukin-6 expression may represent an important component of the excessive inflammatory response observed in cystic fibrosis.
Antipyretic effect of dexamethasone in community-acquired pneumonia
Authors: Stefan M T Vestjens, Simone M C Spoorenberg, Ger T Rijkers, Jan C Grutters, Ewoudt M W van de Garde, Sabine C A Meijvis, Willem Jan W Bos
Journal: European Respiratory Journal (2015)

The cornerstones of treatment for community-acquired pneumonia (CAP) are early diagnosis and initiation of appropriate antibiotic therapy [1]. Despite prevention with vaccination, and optimal antibiotic treatment, CAP is associated with high mortality and morbidity and significant healthcare costs [2, 3]. Adjunctive therapy for CAP could help to reduce disease severity and, indeed, the addition of dexamethasone to antibiotic treatment in patients hospitalised with CAP has shown to reduce the length of hospital stay by 1 day [4]. Recent trials showed similar results [5, 6]. Antipyretic effect of dexamethasone in community-acquired pneumonia does not explain reduced length of hospital stay <http://ow.ly/LTcST> We acknowledge the substantial contribution of Douwe H. Biesma (Dept of Internal Medicine, St. Antonius Hospital, Nieuwegein and Dept of Internal Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands), Hans Hardeman (Dept of Pulmonology, St. Antonius Hospital, Nieuwegein, The Netherlands), Rik Heijligenberg (Dept of Internal Medicine, Gelderse Vallei Hospital, Ede, The Netherlands), Hilde H.F. Remmelts (Dept of Internal Medicine, University Medical Centre Utrecht, Utrecht and Dept of Internal Medicine, Gelderse Vallei Hospital, Ede, The Netherlands), Heleen van Velzen-Blad and G. Paul Voorn (both Dept of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands), to the original trial.
Exisulind in Combination with Celecoxib Modulates Epidermal Growth Factor Receptor, Cyclooxygenase-2, and Cyclin D1 against Prostate Carcinogenesis:<i>In vivo</i>Evidence
Authors: Bhagavathi A. Narayanan, Bandaru S. Reddy, Maarten C. Bosland, Dominick Nargi, Lori Horton, Carla Randolph, Narayanan K. Narayanan
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Nonsteroidal anti-inflammatory drugs mediate anticancer effects by modulating cyclooxygenase-2 (COX-2)-dependent and/or COX-2–independent mechanism(s); however, the toxicity issue is a concern with single agents at higher doses. In this study, we determined the combined effect of celecoxib, a COX-2 inhibitor, along with exisulind (sulindac sulfone/Aptosyn) at low doses in prostate cancer. Experimental Design: We used a sequential regimen of N-methyl-N-nitrosourea + testosterone to induce prostate cancer in Wistar-Unilever rats. Following carcinogen treatment, celecoxib and exisulind individually and their combination at low doses were given in NIH-07 diet for 52 weeks. We determined the incidence of prostatic intraepithelial neoplasia, adenocarcinomas, rate of tumor cell proliferation, and apoptosis. Immunohistochemical and Western blot analysis were done to determine COX-2, epidermal growth factor receptor (EGFR), Akt, androgen receptor, and cyclin D1 expression. Serum prostaglandin E2 and tumor necrosis factor-α levels were determined using enzyme immunoassay/ELISA assays. Results: The rats that received celecoxib in combination with exisulind at low doses showed a significant decrease in prostatic intraepithelial neoplasia and adenocarcinomas as well as an enhanced rate of apoptosis. An overall decrease in COX-2, EGFR, Akt, androgen receptor, and cyclin D1 expression was found associated with tumor growth inhibition. Reduced serum levels of COX-2 protein, prostaglandin E2, and tumor necrosis factor-α indicated anti-inflammatory effects. A strong inhibition of total and phosphorylated form of EGFR (Tyr992 and Tyr845) and Akt (Ser473) was significant in rats given with these agents in combination. Conclusions: In this study, we show for the first time that the combination of celecoxib with exisulind at low doses could prevent prostate carcinogenesis by altering key molecular events.
Implanted Neural Interfaces: Biochallenges and Engineered Solutions
Authors: Warren M. Grill, Sharon E. Norman, Ravi V. Bellamkonda
Journal: Annual Review of Biomedical Engineering (2009)

Neural interfaces are connections that enable two-way exchange of information with the nervous system. These connections can occur at multiple levels, including with peripheral nerves, with the spinal cord, or with the brain; in many instances, fundamental biophysical and biological challenges are shared across these levels. We review these challenges, including selectivity, stability, resolution versus invasiveness, implant-induced injury, and the host-interface response. Subsequently, we review the engineered solutions to these challenges, including electrode designs and geometry, stimulation waveforms, materials, and surface modifications. Finally, we consider emerging opportunities to improve neural interfaces, including cellular-level silicon to neuron connections, optical stimulation, and approaches to control inflammation. Overcoming the biophysical and biological challenges will enable effective high-density neural interfaces for stimulation and recording.
Extent and distribution of CPP deposits in patients affected by calcium pyrophosphate dihydrate deposition disease: an ultrasonographic study
Authors: Georgios Filippou, Emilio Filippucci, Marika Tardella, Ilaria Bertoldi, Marco Di Carlo, Antonella Adinolfi, Walter Grassi, Bruno Frediani
Journal: Annals of the Rheumatic Diseases (2013)

To assess the extent of calcium pyrophosphate dihydrate (CPP) crystal deposition and the distribution of affected sites, using ultrasonography (US), in patients affected by CPP deposition disease (CPPD).42 consecutive patients affected by definite CPPD according to the McCarty criteria were enrolled in the study. All patients underwent an US examination of metacarpophalangeal joints of II, III, IV and V fingers of both hands, wrists and knees, Achilles' tendons and plantar fascia looking for CPP deposits. A dichotomous score for presence/absence of CPP and a semiquantitative score for extent of deposits (0-3: 0, absent; 1, 1-2 spots; 2, more than two spots covering <50% of the structure; 3, deposits covering >50% of the structure) were assigned to each site examined. A site distribution score (total number of affected sites) was then calculated as well as an extent score equal to the sum of the extent scores of all sites.The mean involvement in our patients was 4.7 sites (SD±1.7, range 2-8 sites). The knee was the most affected, site (41 of 42) followed by the wrist (at least one in 37 patients) the Achilles' tendons (23 patients), plantar fascia (11 patients) and metacarpophalangeal joints (four patients). The highest mean values of the extent score were in the menisci, followed by the hyaline cartilage of the femoral condyles and the entheses.The deposition of CPP crystals involves at least two sites with a mean of four sites involved in most patients affected by CPPD and is therefore an oligoarticular or polyarticular disease.
THE EFFECT OF GLUCOCORTICOSTEROIDS ON THE PROLIFERATION AND KINETICS OF PROMONOCYTES AND MONOCYTES OF THE BONE MARROW
Authors: Jan Thompson, Ralph van Furth
Journal: The Journal of Experimental Medicine (1973)

To elucidate mechanisms underlying the prolonged monocytopenia induced in the peripheral blood of mice by injection of a subcutaneous depot of hydrocortisone acetate, the effect of this compound on the production of monocytes and their release from the bone marrow was studied. Hydrocortisone was found to cause a rapid reduction of the bone marrow promonocytes to about 65% of their initial number. The number of monocytes in the bone marrow decreased gradually, over a period of 96 h, to 75% of the initial value. The mitotic activity of the promonocytes was not diminished, as judged from the labeling in vitro with [(3)H]thymidine and the DNA-synthesis and cell-cycle times of these cells. The production of monocytes was only moderately diminished, i.e., to about 80% of the normal amount. The release of monocytes from the bone marrow was found to be influenced by hydrocortisone. After in vivo labeling with [(3)H]thymidine the monocyte-labeling indices were initially significantly higher in hydrocortisone-treated than in normal mice. It is concluded that a decreased production of monocytes in the bone marrow cannot account for the prolonged monocytopenia in the peripheral blood after hydrocortisone administration. However, hydrocortisone interferes with the release of newly formed monocytes from the bone marrow, resulting in a prolonged sojourn of these cells in this compartment.