tbuckley/cabot-search huggingface dataset:
Identification of serous-like cells in the surface epithelium of human bronchioles
Authors: AV Rogers, A Dewar, B Corrin, PK Jeffery
Journal: European Respiratory Journal (1993)

The conductive airways of the mammalian lung are lined by several morphologically distinct cell types, both ciliated and non-ciliated. Of the non-ciliated secretory cells, mucous (goblet), Clara and neuroendocrine cells have been identified in adult human bronchiolar epithelium but, thus far, the serous cell has not. We have examined human membranous and respiratory bronchioles from macroscopically normal peripheral lung (n = 5 cases). For ultrastructural studies, a minimum of five nucleated, non-ciliated cell profiles, containing electron-dense secretory granules, were selected at random from both bronchiolar levels in each case, such that a total of 60 cells was examined. Data from the computer-aided image analysis of the cells indicated that two populations existed, differing in both granule area and granule number per cell p < 0.0005 by discriminant analysis. By visual inspection, the cells fell neatly into two groups: those which, were predominantly serous-like in type, and those which were "Clara". In the membranous bronchioles, serous-like cells had a mean(SEM) granule area per cell of 3.67(0.62) microns 2 and Clara cells 0.47(0.07) microns 2 (p < 0.001). Also, in the membranous bronchiole, the mean(SEM) number of granules in serous-like cells was 40(4.7) and in Clara cells 10(1.1) (p < 0.001). At the respiratory bronchiolar level, the corresponding means were similar to those of the membranous bronchioles and, likewise, serous and Clara cells were significantly different. Thus, our data, indicate that serous cells are present in the adult human bronchiole.
A Novel Virulence Gene in <i>Klebsiella pneumoniae</i> Strains Causing Primary Liver Abscess and Septic Metastatic Complications
Authors: Chi-Tai Fang, Yi-Ping Chuang, Chia-Tung Shun, Shan-Chwen Chang, Jin-Town Wang
Journal: The Journal of Experimental Medicine (2004)

Primary Klebsiella pneumoniae liver abscess complicated with metastatic meningitis or endophthalmitis is a globally emerging infectious disease. Its pathogenic mechanism remains unclear. The bacterial virulence factors were explored by comparing clinical isolates. Differences in mucoviscosity were observed between strains that caused primary liver abscess (invasive) and those that did not (noninvasive). Hypermucoviscosity correlated with a high serum resistance and was more prevalent in invasive strains (52/53 vs. 9/52; P &amp;lt; 0.0001). Transposon mutagenesis identified candidate virulence genes. A novel 1.2-kb locus, magA, which encoded a 43-kD outer membrane protein, was significantly more prevalent in invasive strains (52/53 vs. 14/52; P &amp;lt; 0.0001). The wild-type strain produced a mucoviscous exopolysaccharide web, actively proliferated in nonimmune human serum, resisted phagocytosis, and caused liver microabscess and meningitis in mice. However, magA− mutants lost the exopolysaccharide web and became extremely serum sensitive, phagocytosis susceptible, and avirulent to mice. Virulence was restored by complementation using a magA-containing plasmid. We conclude that magA fits molecular Koch's postulates as a virulence gene. Thus, this locus can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease.
Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair
Authors: Xinping Zhang, Edward M. Schwarz, Donald A. Young, J. Edward Puzas, Randy N. Rosier, Regis J. O’Keefe
Journal: Journal of Clinical Investigation (2002)

Preclinical and clinical studies suggest a possible role for cyclooxygenases in bone repair and create concerns about the use of nonsteroidal antiinflammatory drugs in patients with skeletal injury. We utilized wild-type, COX-1–/–, and COX-2–/– mice to demonstrate that COX-2 plays an essential role in both endochondral and intramembranous bone formation during skeletal repair. The healing of stabilized tibia fractures was significantly delayed in COX-2–/– mice compared with COX-1–/– and wild-type controls. The histology was characterized by a persistence of undifferentiated mesenchyme and a marked reduction in osteoblastogenesis that resulted in a high incidence of fibrous nonunion in the COX-2–/– mice. Similarly, intramembranous bone formation on the calvaria was reduced 60% in COX-2–/– mice following in vivo injection of FGF-1 compared with either COX-1–/– or wild-type mice. To elucidate the mechanism involved in reduced bone formation, osteoblastogenesis was studied in bone marrow stromal cell cultures obtained from COX-2–/– and wild-type mice. Bone nodule formation was reduced 50% in COX-2–/– mice. The defect in osteogenesis was completely rescued by addition of prostaglandin E2 (PGE2) to the cultures. In the presence of bone morphogenetic protein (BMP-2), bone nodule formation was enhanced to a similar level above that observed with PGE2 alone in both control and COX-2–/– cultures, indicating that BMPs complement COX-2 deficiency and are downstream of prostaglandins. Furthermore, we found that the defect in COX-2–/– cultures correlated with significantly reduced levels of cbfa1 and osterix, two genes necessary for bone formation. Addition of PGE2 rescued this defect, while BMP-2 enhanced cbfa1 and osterix in both COX-2–/– and wild-type cultures. Finally, the effects of these agents were additive, indicating that COX-2 is involved in maximal induction of osteogenesis. These results provide a model whereby COX-2 regulates the induction of cbfa1 and osterix to mediate normal skeletal repair.
Intralobar pulmonary sequestration in conjunction with bronchial isomerism.
Authors: K K Mohan, N Kramer, M L Margolis, R M Steiner, H E Cohn
Journal: Thorax (1983)

<h3></h3> The traditional hospice setup has been developed with silos across therapeutic services - resulting in families receiving multiple referrals for support with little or no understanding of the wider influences and having to retell their stories. Combining Social work, Counselling, Physio, OT, Creative therapy, Complementary therapy, Family support and Spiritual care into a wellbeing department streamlines the process with one referral, one holistic assessment, one MDT and one family-centred therapeutic plan. Families access the right support at the right time. <h3>Aims</h3> Early intervention; holistic family support; integrated services; robust referral pathways; preventing crisis. <h3>Methods</h3> Internal audits. Review of current counselling demand. Review of best practice guidance. Embedding a social care model for social and wellbeing needs. Client feedback. Evaluations. Referral trends. <h3>Results</h3> Reduction in counselling waiting lists. Improved early intervention to prevent crisis. Streamlined referral processes – one referral to wellbeing services. Improved multidisciplinary working. Strengthen relationships with stakeholders. Embedded holistic family assessments. <h3>Conclusion</h3> Therapeutic services improve wellbeing and should be integrated. Families consistently tell professionals that they do not want to keep repeating their stories and communication is key. To provide person-centred care we must look at all the influencing factors and family dynamics and support play a key role. To improve family wellbeing, we must look at the whole picture. This way of working is innovative in hospices but best practice in all therapy and family-based settings. Further research in hospices could strengthen this practice.
Primary cutaneous B-cell lymphoma mimicking pyoderma gangrenosum: first-line treatment with rituximab
Authors: M-C. Lami, P. Vabres, B. Dreyfus, T. Germain, G. Guillet
Journal: British Journal of Dermatology (2004)

Journal Article Primary cutaneous B‐cell lymphoma mimicking pyoderma gangrenosum: first‐line treatment with rituximab Get access M‐C. Lami, M‐C. Lami Departments of Dermatology, Haematology E‐mail: cca.dermato@chu‐poitiers.fr Search for other works by this author on: Oxford Academic Google Scholar P. Vabres, P. Vabres Departments of Dermatology, Haematology Search for other works by this author on: Oxford Academic Google Scholar B. Dreyfus, B. Dreyfus Departments of Dermatology, Haematology Search for other works by this author on: Oxford Academic Google Scholar T. Germain, T. Germain Oncology, CHU Poitiers, France Search for other works by this author on: Oxford Academic Google Scholar G. Guillet G. Guillet Departments of Dermatology, Haematology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 1, 1 July 2004, Pages 250–252, https://doi.org/10.1111/j.1365-2133.2004.06080.x Published: 01 July 2004
New Evidence Implicating 4‐Hydroxynonenal in the Pathogenesis of Osteoarthritis In Vivo
Authors: Qin Shi, Jamilah Abusarah, Charlotte Zaouter, Florina Moldovan, Julio C. Fernandes, Hassan Fahmi, Mohamed Benderdour
Journal: Arthritis & Rheumatology (2014)

To demonstrate the involvement of 4-hydroxynonenal (HNE), a very reactive aldehyde derived from lipid peroxidation, in the pathogenesis of osteoarthritis (OA) in vivo.In the first experimental protocol, OA was induced by anterior cruciate ligament transection (ACLT) of the right knees of crossbred dogs (n = 6 per group). The animals were treated with placebo or HNE-trapping carnosine (5 or 20 mg/kg/day) orally for 8 weeks. Another group of dogs was treated for 4 weeks with 20 mg/kg/day of carnosine starting 4 weeks after surgery. Sham-operated dogs served as controls. In the second experimental protocol, a pathophysiologic dose of HNE (80 nmoles/ml) or vehicle was injected weekly into the right knee joints of crossbred dogs (n = 6 per group) for 8 weeks. Articular cartilage was subjected to macroscopic, histomorphologic, and immunohistochemical analyses. Cartilage-degrading enzymes and oxidative stress-related products were assessed in synovial fluid and cartilage explants. Markers of inflammation were evaluated in synovium and synovial fluid.In dogs that had undergone ACLT, carnosine treatment reduced the severity and histopathology score of OA cartilage lesions and also decreased HNE-protein adducts, pentosidine, nitrosylated proteins, cartilage-degrading enzymes, and markers of inflammation. Intraarticular injection of HNE induced cartilage lesions, as assessed by macroscopic and microscopic criteria. Cartilage-degrading enzymes and markers of inflammation increased in HNE-treated dogs.This is the first in vivo study to demonstrate the pathophysiologic role of HNE in OA. That carnosine abolishes HNE production and a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.
Prediction of Lymph Node Metastasis by Analysis of Gene Expression Profiles in Primary Lung Adenocarcinomas
Authors: Liqiang Xi, James Lyons-Weiler, Michael C. Coello, Xin Huang, William E. Gooding, James D. Luketich, Tony E. Godfrey
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Lymph node status is a strong predictor of outcome for lung cancer patients. Recently, several reports have hinted that gene expression profiles of primary tumor may be able to predict node status. The goals of this study were to determine if microarray data could be used to accurately classify patients with regard to pathologic lymph node status, and to determine if this analysis could identify patients at risk for occult disease and worse survival. Experimental Design: Two previously published lung adenocarcinoma microarray data sets were reanalyzed. Patients were separated into two groups based on pathologic lymph node positive (pN+) or negative (pN0) status, and prediction analysis of microarray (PAM) was used for training and validation to classify nodal status. Overall survival analysis was performed based on PAM classifications. Results: In the training phase, a 318-gene set gave classification accuracy of 88.4% when compared with pathology. Survival was significantly worse in PAM-positive compared with PAM-negative patients overall (P &amp;lt; 0.0001) and also when confined to pN0 patients only (P = 0.0037). In the validation set, classification accuracy was again 94.1% in the pN+ patients but only 21.2% in the pN0 patients. However, among the pN0 patients, recurrence rates and overall survival were significantly worse in the PAM-positive compared with PAM-negative patients (P = 0.0258 and 0.0507). Conclusions: Analysis of gene expression profiles from primary tumor may predict lymph node status but frequently misclassifies pN0 patients as node positive. Recurrence rates and overall survival are worse in these “misclassified” patients, implying that they may in fact have occult disease spread.
Tocilizumab for multirefractory adult-onset Still’s disease
Authors: M De Bandt, B Saint-Marcoux
Journal: Annals of the Rheumatic Diseases (2008)

Adult-onset Still’s disease (AOSD) is a multisystemic inflammatory disease of unknown cause, characterised by daily spiking fever, rash, leucocytosis and arthritis. Cytokines such as interleukin (IL)1, 6 and 18, interferon γ, tumour necrosis factor are thought to have a role in the pathogenesis of the disease.1 2 Treatments such as non-steroidal anti-inflammatory drugs, steroids, methotrexate (MTX), gold, azathioprine, leflunomide, ciclosporin and biological agents (tumour necrosis factor blockers, IL1 receptor antagonist or rituximab) can help in the management of patients, depending on presentation and disease course.3–5

We report on a young woman with refractory AOSD successfully treated with anti-IL6 receptor antibody (tocilizumab), whose efficacy has been shown in …
Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100)
Authors: Y. Loriot, D. Bianchini, E. Ileana, S. Sandhu, A. Patrikidou, C. Pezaro, L. Albiges, G. Attard, K. Fizazi, J.S. De Bono, C. Massard
Journal: Annals of Oncology (2013)
Facilitated physical activity as a treatment for depressed adults: randomised controlled trial
Authors: M. Chalder, N. J. Wiles, J. Campbell, S. P. Hollinghurst, A. M. Haase, A. H. Taylor, K. R. Fox, C. Costelloe, A. Searle, H. Baxter, R. Winder, C. Wright, K. M. Turner, M. Calnan, D. A. Lawlor, T. J. Peters, D. J. Sharp, A. A. Montgomery, G. Lewis
Journal: BMJ (2012)

<b>Objective</b> To investigate the effectiveness of facilitated physical activity as an adjunctive treatment for adults with depression presenting in primary care. <b>Design</b> Pragmatic, multicentre, two arm parallel randomised controlled trial. <b>Setting</b> General practices in Bristol and Exeter. <b>Participants</b> 361 adults aged 18-69 who had recently consulted their general practitioner with symptoms of depression. All those randomised had a diagnosis of an episode of depression as assessed by the clinical interview schedule-revised and a Beck depression inventory score of 14 or more. <b>Interventions</b> In addition to usual care, intervention participants were offered up to three face to face sessions and 10 telephone calls with a trained physical activity facilitator over eight months. The intervention was based on theory and aimed to provide individually tailored support and encouragement to engage in physical activity. <b>Main outcome measures</b> The primary outcome was self reported symptoms of depression, assessed with the Beck depression inventory at four months post-randomisation. Secondary outcomes included use of antidepressants and physical activity at the four, eight, and 12 month follow-up points, and symptoms of depression at eight and 12 month follow-up. <b>Results</b> There was no evidence that participants offered the physical activity intervention reported improvement in mood by the four month follow-up point compared with those in the usual care group; adjusted between group difference in mean Beck depression inventory score −0.54 (95% confidence interval −3.06 to 1.99; P=0.68). Similarly, there was no evidence that the intervention group reported a change in mood by the eight and 12 month follow-up points. Nor was there evidence that the intervention reduced antidepressant use compared with usual care (adjusted odds ratio 0.63, 95% confidence interval 0.19 to 2.06; P=0.44) over the duration of the trial. However, participants allocated to the intervention group reported more physical activity during the follow-up period than those allocated to the usual care group (adjusted odds ratio 2.27, 95% confidence interval 1.32 to 3.89; P=0.003). <b>Conclusions</b> The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone. <b>Trial registration</b> Current Controlled Trials ISRCTN16900744.
Response to Letter Regarding Article, “Primary Results From the SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) Trial: A Randomized Trial Comparing Empirical, Echocardiography-Guided and Algorithmic Atrioventricular Delay Programming in Cardiac Resynchronization Therapy”
Authors: Kenneth A. Ellenbogen, Michael R. Gold, Timothy E. Meyer, Ignacio Fernández Lozano, Suneet Mittal, Alan D. Waggoner, Bernd Lemke, Jagmeet P. Singh, Francis G. Spinale, Jennifer E. Van Eyk, Jeffrey Whitehill, Stanislav Weiner, Maninder Bedi, Joshua Rapkin, Kenneth M. Stein
Journal: Circulation (2011)

Resynchronization Therapy"We appreciate the authors' careful review of our manuscript and prepared the following response to their comments.The first comment is that the SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial was underpowered to detect the additional response to atrioventricular (AV) optimization.Importantly, the authors performed a post hoc power calculation, basing their calculations on the observed fixed-group response.These calculations do not have the same validity as prospective power calculations and must be interpreted with great caution. 1 Second, the noninferiority margin of 15 mL for a left ventricular end-systolic volume difference from baseline to 6 months post-cardiac resynchronization therapy was chosen by the SMART-AV Steering Committee as reflecting a clinically meaningful difference.Moreover, the primary and secondary end points and the statistical analysis plan were reviewed with the Food and Drug Administration before the initiation of the SMART-AV trial and have been previously published in detail. 2 Third, a larger trial would always provide more power to detect smaller differences.Based on the trial design, we cannot exclude the possibility that AV optimization with either echo or the SmartDelay can lead to smaller changes in these end points.The 95% confidence limits for the median differences observed in the trial suggest that the true difference in improvement in left ventricular end-systolic volume between the echo and fixed arms is between 12 mL and Ϫ3 mL.The 95% confidence limits for the median differences observed in the trial suggest that the true difference in improvement in left ventricular end-systolic volume between the SmartDelay and fixed arms is between 11 mL and Ϫ3 mL.Finally, this trial should not be interpreted as providing evidence "that AV optimization does not work for anyone."In fact, we explicitly conclude that "these data do not exclude possible utility in selected patients who do not respond to CRT," and we provide the results of a subgroup analysis suggesting a possible benefit to AV optimization in women, as well.
Anti-contractile and anti-proliferative responses in human pulmonary arterial smooth muscle cells induced by ACT-333679, the active metabolite of selexipag, a non-prostanoid selective prostacyclin receptor agonist
Authors: John Gatfield, Katalin Menyhart, Oliver Nayler
Journal: European Respiratory Journal (2014)

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vasoconstriction and vascular remodeling. Pulmonary arterial smooth muscle cells (PASMC) are major contributors to PAH pathology by displaying increased contractile and proliferative behavior. Stimulation of the prostacyclin (IP) receptor in PASMC leads to intracellular cyclic AMP accumulation, and increases in cAMP levels are known to reduce cellular proliferation and to inhibit cellular contraction via cellular hyperpolarization and cytoskeletal desensitization.  In this study we analyzed the signaling cascades and phenotypic changes in human PASMC induced by the non-prostanoid IP receptor agonist ACT-333679, the active metabolite of the oral experimental PAH drug selexipag. ACT-333679 potently induced intracellular cAMP accumulation (EC 50 =265 nM) and mediated long-lasting (>10h) membrane potential hyperpolarization (EC 50 =32 nM). Impedance measurements showed that ACT-333679 induced long-lasting (>10h) and pronounced PASMC shape change (EC 50 = 4.3 nM). Additionally, ACT-333679 inhibited platelet-derived growth factor-BB-stimulated proliferation ( 3 H-thymidine incorporation) in PASMC (IC 50 =2.9 nM).  In summary, ACT-333679 activated a GPCR signaling cascade in PASMC leading to cAMP accumulation, cellular hyperpolarization and shape change, as well as inhibition of cellular proliferation. ACT-333679 potency increased ∼100-fold from the receptor-proximal cAMP readout to the receptor-distal therapeutically-relevant phenotypic readouts.
Identification of MicroRNA-214 as a negative regulator of colorectal cancer liver metastasis by way of regulation of fibroblast growth factor receptor 1 expression
Authors: Dong-liang Chen, Zhi-qiang Wang, Zhao-lei Zeng, Wen-jing Wu, Dong-sheng Zhang, Hui-yan Luo, Feng Wang, Miao-zhen Qiu, De-shen Wang, Chao Ren, Feng-hua Wang, Lucia J. Chiao, Helene Pelicano, Peng Huang, Yu-hong Li, Rui-hua Xu
Journal: Hepatology (2014)

The purpose of this study was to identify microRNAs (miRNAs) involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. A panel of eight miRNAs were confirmed to be significantly and differentially expressed between CRC tissues with and without liver metastases through quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis in the 32 patients. In a validated cohort of 99 CRC patients (44 with and 55 without liver metastases), only miR-214 was validated to be significantly down-regulated in CRC with liver metastases, which was associated with an unfavorable prognosis. Ectopic expression of miR-214 suppressed proliferation, migration, and invasion in vitro , tumor growth and liver metastasis in an in vivo xenograft mouse model, whereas miR-214 knockdown promoted proliferation, migration, and invasion in CRC cell lines. Further studies indicated that fibroblast growth factor receptor 1 (FGFR1) was a potential target of miR-214. Restoring miR-214 expression in CRC cells decreased endogenous FGFR1 messenger RNA (mRNA) and protein levels. FGFR1 knockdown mimicked the tumor suppressive effect of miR-214 on CRC cells, while reintroduction of FGFR1 abolished the tumor suppressive effect of miR-214 on CRC cells. Moreover, miR-214 expression levels were inversely correlated with FGFR1 in CRC patients. Conclusion : Down-regulation of miR-214 expression was correlated with increased FGFR1 expression levels, which may contribute to increased CRC liver metastasis. miR-214 may serve as a potential marker to predict survival, and the miR-214-FGFR1 axis may be a therapeutic target in CRC patients. (Hepatology 2014;60:598–609)