tbuckley/cabot-search huggingface dataset:
Systemic sclerosis-like histopathological features in the myocardium of uPAR-deficient mice
Authors: Mirko Manetti, Irene Rosa, Marilena Fazi, Serena Guiducci, Peter Carmeliet, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> Cardiomyopathy is among the leading causes of death from systemic sclerosis (SSc). Urokinase-type plasminogen activator receptor (uPAR)-deficient mice have been recently reported to display important histopathological hallmarks of SSc, including dermal fibrosis, reduced dermal capillary density, and pulmonary fibrosis. Here, we investigated whether uPAR-deficient mice could display the histopathological features of SSc-related cardiomyopathy. <h3>Methods</h3> Ventricular myocardial specimens from uPAR-deficient and wild-type mice at 12 and 24 weeks of age were analysed by both light microscopy and transmission electron microscopy. Picrosirius red staining and hydroxyproline content of myocardial specimens were quantified. Myofibroblast and microvessel counts were determined by immunofluorescence for α-smooth muscle actin and CD31, respectively. Endothelial cell apoptosis was assessed by a combined TUNEL/CD31 immunofluorescence assay. Expression of uPAR in human SSc and control ventricular myocardial autopsy specimens was determined by immunohistochemistry. <h3>Results</h3> The myocardium of 24-week-old uPAR-deficient mice displayed focal ischaemic lesions with cardiomyocyte hypertrophy, myofibril rarefaction and contraction band necrosis. At 24 weeks of age, interstitial and perivascular collagen deposition and myofibroblast counts were significantly greater in myocardial tissue of uPAR-deficient mice than in wild-type mice. In uPAR-deficient mice, myocardial fibrosis was paralleled by microvascular endothelial cell apoptosis and reduced capillary density. uPAR expression was significantly downregulated in the myocardium of patients with SSc. <h3>Conclusions</h3> Typical histopathological features of SSc-related cardiomyopathy are mimicked by uPAR-deficient mice. The downregulation of uPAR in the myocardium of patients with SSc may suggest similar underlying pathogenetic mechanisms. uPAR-deficient mice could be used as a preclinical model to study the mechanisms and therapeutic approaches of myocardial involvement in SSc.
Effects of a very low energy building scenario in Europe on air pollution and health
Authors: Jakob H. Bønløkke, Gitte J. Holst, Torben Sigsgaard, Ulrik Korsholm, Jens H. Sørensen
Journal: European Respiratory Journal (2013)

Substantial amounts of energy are used for domestic heating. Accordingly domestic heating significantly influences climate and air pollution. We investigated the effects of a very low energy building scenario (VLEB) with an annual retrofit rate of 2% in Europe on air pollution and the resulting health benefits.  Energy savings from 2005 to 2020 due to insulation were calculated by comparing a business as usual (baseline) and the VLEB scenario. The resulting changes in emissions were entered in a Comprehensive Air-Quality Model with extensions, using meteorology for 2009¹. Mean annual changes in particulate matter were calculated for each country. Demographic data were extracted from WHO databases. Changes in health effects per μg/m³ change in mean annual PM were derived from published reviews as 0.6% in all-cause mortality among adults and 7.7 new persistent cases of chronic bronchitis per 100,000 adults.  The mean annual change in PM2.5 varied between -0.008 μg/m³ (Finland) and -0.538 μg/m³ (Belgium). The number of life-years gained among adults varied from 0.9/100,000 persons/yr to 54.5/100,000 persons/yr - the mean being 24.5/100,000/yr. The total number of life-years gained annually varied from 31 in Finland to 22524 in Germany, totalling 75089 life-years in Europe. A total of 6899 cases of persistent chronic bronchitis were avoided annually under the VLEB scenario compared with baseline.  In conclusion, a VLEB scenario in Europe would have substantial benefits on health by lowering air pollution. The saved societal costs from such benefits should be taken into account when planning mitigation of global warming by energy consumption reductions.  ¹Korsholm US et al., Atmos Environ. 2012.
Tobacco control and smoking pattern among medical students in Kathmandu University Teaching Hospital
Authors: Pankaj Pant, Prasant Khatiwada
Journal: European Respiratory Journal (2013)

Background  As of 2002, about 20% of young teens (13–15years) smoke worldwide. Everyday 80-100 thousand children start smoking. Half of those who begin smoking in their adolescence are predicted to continue it for 15 to 20 years. In this context, to have adequate knowledge of smoking related diseases and skills in smoking cessation is very important for medical students, the future medical practitioners.This study assessed the knowledge about tobacco related diseases and their own behavior among 153 medical students of Kathmandu University Teaching Hospital.  Methods  Qualitative and quantitative approaches were used for data collection from 153 medical students from December 2011 to May 2012. Questionnaires were handed out to the participants, and discussions were carried out in five groups of these students.  Results  The majority of the students had good knowledge of tobacco/smoking and its consequences. About 24% of the total students were current or ex-smokers. Only 10% had heard of Framework Convention on Tobacco Control in Nepal. Eighty-nine students had over 80% knowledge of the warning signs from tobacco use, among them 83% knew the nine risk factors for lung cancer. Approximately 95% of all participants confirmed passive exposure to smoking, where majority (75%) was in friends circle. Forty percent of them knew someone who had ever suffered from cancer.  Conclusion  All medical students who know about any cancers may not necessarily have knowledge about lung cancers. Their perception about the cause of lung cancer may be influenced by their smoking behavior. Awareness about national policies needs to be increased.
The species-specific inflammatory response of colonising bacteria in stable COPD
Authors: Richa Singh, Anant Patel, Alex Mackay, Davinder Garcha, Beverly Kowlessar, Simon Brill, Ray Sapsford, Louise Donnelly, Peter Barnes, Gavin Donaldson, Jadwiga Wedzicha
Journal: European Respiratory Journal (2013)

Potentially pathogenic micro-organisms (PPMs) are frequently isolated from stable COPD patients. We hypothesised that the degree of airway & systemic inflammation is dependent on species of PPM.

Sputa & sera collected from stable patients in the London COPD Cohort were analysed by qPCR to detect H. influenzae (HI) , M. catarrhalis (MC) and S. pneumoniae (SP), ELISAs for airway IL-8, IL-1β & MPO, & sera CRP was measured. 183 paired sputa & sera from 99 stable patients were included.

Clinical characteristics are shown in Table 1.

View this table:

Baseline Characteristics n=99





PPMs were detected in 64/183 of sputa. HI & SP were equally prevalent & there was no significant difference between their loads (p=0.49). MC load was significantly higher than both HI (p<0.001) & SP (p=0.001).

Patients with lower airway bacterial colonisation (LABC) by any PPM had significantly higher airway cytokines than non-LABC patients (all p<0.001). HI-colonised but not SP- or MC-colonised patients had significantly higher airway cytokines than non-LABC patients (all p<0.05, Figure 1). There was no significant difference between CRP in non-LABC & LABC patients, or between non-LABC patients & different PPMs.

![Figure][1] 



LABC patients have higher airway, but not systemic inflammation, & this is associated with HI. Targeting HI in stable COPD may potentially help to decrease airway inflammation.

 [1]: pending:yes
Value of KRAS as prognostic or predictive marker in NSCLC: results from the TAILOR trial
Authors: E. Rulli, M. Marabese, V. Torri, G. Farina, S. Veronese, A. Bettini, F. Longo, L. Moscetti, M. Ganzinelli, C. Lauricella, E. Copreni, R. Labianca, O. Martelli, S. Marsoni, M. Broggini, M.C. Garassino
Journal: Annals of Oncology (2015)
The long noncoding RNA HOTAIR has tissue and cell type-dependent effects on HOX gene expression and phenotype of urothelial cancer cells
Authors: Judith Heubach, Juliana Monsior, René Deenen, Günter Niegisch, Tibor Szarvas, Christian Niedworok, Wolfgang Arthur Schulz, Michèle Janine Hoffmann
Journal: Molecular Cancer (2015)

Urothelial carcinoma (UC) is the fifth most common cancer in the developed world. Delineation of differentiation subtypes in UC highlighted the importance of aberrant differentiation. Understanding underlying mechanisms may facilitate diagnosis and development of efficient therapy strategies. It is well accepted that epigenetic mechanisms are involved. Long noncoding RNAs (lncRNAs), a new class of epigenetic factors, are thought to mediate molecular differences between cell types to control cellular identity. The present study focuses on the lncRNA HOTAIR, originating from the HOXC locus. Its overexpression induces an aggressive phenotype in many cancers and aberrant expression of homeotic HOX transcription factors, especially HOXD10, that regulate differentiation and tissue homeostasis. The aim of the present study was to determine the functional role of HOTAIR in UC with regard to aggressive phenotype, regulation of aberrant differentiation and altered HOX gene expression.We determined RNA expression levels of HOTAIR and HOX genes in UC tissues and cell lines. Knockdown of HOTAIR and ectopic overexpression was performed to determine the effect on reported target genes in UC. Cell lines were stably transfected with HOTAIR to investigate changes in phenotype and HOX gene expression.HOTAIR was overexpressed in approximately half of UC tissues and cell lines. Effects of HOTAIR overexpression differed between cell lines. Whereas VM-CUB1 cells acquired the expected phenotype with increased proliferation, clonogenicity, anchorage independent growth, migratory activity and epithelial-to-mesenchymal transition, 5637 cells grew more slowly displaying induction of senescence and related immune response genes. Other UC lines showed intermediate effects. Expression profiling revealed divergent effects on HOX genes, cell cycle regulators and differentiation according with the phenotypic differences between HOTAIR-overexpressing VM-CUB1 and 5637 cells.Our data indicate that HOTAIR overexpression may affect differentiation state and aggressiveness of UC cells, but in a cell-type dependent manner. Our functional studies and the comparison of our expression data sets with those from other cancer cell types, which revealed minimal overlaps, indicate that effects of HOTAIR are strongly tissue-dependent and can even differ within one cancer type. Thus, HOTAIR functions and target genes cannot simply be transferred from one cancer type to the other.
Nutrition and mortality in hemodialysis.
Authors: J Bergström
Journal: Journal of the American Society of Nephrology (1995)

Protein-energy malnutrition is present in a large proportion of maintenance hemodialysis (HD) patients, and it is associated with increased morbidity and mortality. The protein requirements are increased because of the presence of endocrine and metabolic factors related to loss of renal function, the HD procedure, and comorbidity factors, which all stimulate net protein catabolism. The intake protein and energy are frequently reduced because of the underlying disease, psychosocial factors, and uremic anorexia. However, the extent to which underdialysis contributes to anorexia and malnutrition is still not well defined. Malnutrition is generally not recognized as a common direct cause of death as reflected in health statistics, except in the highest age groups. Anthropometric and biochemical signs of malnutrition are associated with increased mortality. A low serum albumin level is a strong predictive risk factor that may reflect not only or mainly protein malnutrition but also the influence of several other morbidity factors (overhydration, infection, chronic disease and others) that may entail an increased risk of death. Low levels of serum creatinine (low muscle mass), serum cholesterol (energy depletion), and BUN and low urea appearance rate (low protein intake) are also correlated to increased mortality. For the prevention and treatment of HD-associated malnutrition, measures should be taken to correct factors that may suppress appetite and increase net protein catabolism (underdialysis, acidosis, low energy intake, comorbid conditions, psychosocial and economic factors). Dietary advice should be given with the aim of ensuring an adequate intake of protein- and energy-giving products. Intradialytic parenteral nutrition may have positive effects on nutritional status when other measures fail. However, the indications for such treatment have not yet been well defined, and the effects on survival, morbidity, and quality of life are not sufficiently well proved. More and better data, generated in prospective, well-controlled studies, are obviously needed before intradialytic parenteral nutrition can be generally recommended as therapy for malnourished HD patients.
Defective Natural Killer Activity Within Human Ovarian Tumors: Low Numbers of Morphologically Defined Effectors Present in Situ&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Martino Introna, Paola Allavena, Andrea Biondi, Nicoletta Colombo, Antonello Villa, Alberto Mantovani
Journal: JNCI Journal of the National Cancer Institute (1983)

Tumor-associated Iymphocytes (TAL) were isolated from 17 ascites and 7 solid ovarian carcinomas. TAL had defective natural killer (NK) activity against K562. Large granular Iymphocytes, the morphologically identified effectors of NK activity, were poorly represented in TAL from ovarian carcinomas as compared to peripheral blood Iymphocytes from the same patients or from normal donors. Similar results were obtained when effectors of NK activity were identified with an anti-NK (HNK-1) monoclonal antibody. When four TAL preparations were separated on discontinuous Percoll gradients, they were able to be enriched for NK activity and large granular Iymphocyte morphology in the lower density fractions as observed with blood. These observations suggested that a low concentration of the relevant effector cells was the major factor determining the defective NK cytotoxicity of lymphoid cells associated with these human neoplasms.
Education of asthmatic children: Impact on the perception and on the control of the disease and usefulness of an asthma logbook
Authors: Emna Ben Salah, Hanadi Ouali, Jamel Ammar, Anissa Berrais, Agnés Hamzaoui
Journal: European Respiratory Journal (2013)

Asthma is the most common chronic disease in children. Systematic patient’s education positively affects the management of asthma.  The aim of this prospective study is to assess the impact of education on knowledge, perception and control of asthma through an individual education associated with an illustrated logbook prepared for this program.  Between August 2011 and January 2012, a questionnaire in Arabic dialect is administered to 40 asthmatic children (3-16 years) and their parents on consultation day. Patients and parents than had an education session focused on the mechanisms, triggers and medication of asthma, on the adherence to treatment and on patient’s quality of life. Visual media and an asthma logbook were used. An assessment with same questionnaire is conducted 3 months later.  There is a significant improvement in parents knowledges of the disease (52, 5% vs 92, 5% ,p=0,001) mechanisms(85% vs 95%, p=0,044), asthma treatment (32,5% vs 70%, p=0,001) and use of asthma self-management for acute episodes (70% vs 95%, p=0,003). In patients group, results showed improvement in the knowledge of the disease (57, 5 vs 62,5% ,p=0,001) and its treatment(7,5% vs 40%, p=0,001). A better control of asthma is also obtained (70% vs 95, p=0,000) with the use of asthma action plan (45% vs 95%,p=0,000) However, asthma perception was not significantly different after education(70% vs 80%, p=0,1). Educational programs should be considered as part of the care routine for young asthmatic patients and their parents and have to be continuously maintained in order to improve the perception of the disease especially in our country where asthma still remains as taboo.
The role of cytoreduction for metastatic and recurrent colorectal cancer in the era of multidisciplinary treatments.
Authors: K. Tanaka, Y. Inoue, Y. Toiyama, J. Hiro, T. Iwata, S. Saigusa, M. Ohi, C. Miki, S. Kageyama, M. Kusunoki
Journal: Journal of Clinical Oncology (2010)

e14091 Background: Advance in chemotherapy for colorectal cancer (CRC) has been increasing the opportunity to resect metastatic disease which was initially unresectable with possible curative intent. Cytoreduction is a standard modality in advanced ovarian cancer with significant better survival. According to Norton-Simon hypothesis, the rationale of cytoreduction is that the less the amount of tumor cells is, the better tumor cells respond to chemotherapy. This study aimed to evaluate the role of cytoreduction for metastatic and recurrent colorectal cancer in the era of multidisciplinary treatments. Methods: We performed a retrospective review of 201 patients with unresectable primary, synchronous metastatic (stage IV), and metachronous metastatic (recurrent) CRC at our institution from 2000 to 2009. All patients received 5-fluorouracil (5-FU)-based, oxaliplatin- or irinotecan-based triple-drug chemotherapy (infusional 5-FU, leucovorin, and oxaliplatin; infusional 5-FU, leucovorin, and irinotecan) with or without bevacizumab. Cytoreductive procedures included the resection of primary and/or metastatic disease or radiofrequency ablation (RFA) for metastatic disease in either debulking or possible curative setting. Results: Seventy out of 201 patients (34.8%) had cytoreduced primary or metastatic tumor in combination with systemic chemotherapy (cytoreduction group). Resection and RFA were performed for 51 and 34 lesions, respectively. Patients' performance status and chemotherapy response were significantly better in cytoreduction group (p < 0.01). A possible curative cytoreduction was achieved in 23 (32.9%) of 70 patients. The remaining 47 patients underwent debulking cytoreduction. Cytoreduction group had significantly better survival than non-cytoreduction (chemotherapy alone) group (p < 0.0001). The duration from initial chemotherapy to cytoreduction was significantly shorter in chemotherapy with bezacizumab (p < 0.01). Conclusions: Cytoreduction may become the standard care for metastatic and recurrent colorectal cancer as one of multidisciprinary treatment modalities with either debulking or possible curative intent. No significant financial relationships to disclose.
HISTOLOGICAL LESIONS OF MUSCLE IN DERMATOMYOSITIS..
Authors: P. Le COULANT, L. TEXIER
Journal: British Journal of Dermatology (1957)

Journal Article HISTOLOGICAL LESIONS OF MUSCLE IN DERMATOMYOSITIS.: Differentiation from Related Musculo‐cutaneous Syndromes. Get access P. Le COULANT, P. Le COULANT Bordeaux Search for other works by this author on: Oxford Academic Google Scholar L. TEXIER L. TEXIER Bordeaux Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 9, 1 September 1957, Pages 299–310, https://doi.org/10.1111/j.1365-2133.1957.tb13275.x Published: 01 September 1957
Efficacy and safety of follow-up field treatment of actinic keratosis with ingenol mebutate 0·015% gel: a randomized, controlled 12-month study
Authors: C. Garbe, N. Basset-Seguin, Y. Poulin, T. Larsson, M.L. Østerdal, R. Venkata, J.T. Lear
Journal: British Journal of Dermatology (2015)

Ingenol mebutate (IngMeb) is a novel patient-applied topical field therapy for actinic keratosis.To demonstrate the efficacy and safety of follow-up IngMeb field treatment of actinic keratoses (AKs) present at 8 weeks after initial treatment or emerging in a previously cleared field.In this phase III, randomized, double-blind study in patients with 4-8 clinically visible AKs within a contiguous 25-cm(2) treatment area on the face or scalp, all patients were treated initially with IngMeb 0·015% gel for three consecutive days. If lesions were present in the field at 8 weeks, or emerged at weeks 26 or 44, patients were randomized (2 : 1) to follow-up IngMeb or vehicle gel for three consecutive days. The main outcome was complete clearance rates of AKs 8 weeks after randomization.Of 450 patients who received initial treatment with IngMeb, 61·6% demonstrated complete clearance at 8 weeks. Patients with AKs present at 8 weeks or emerging at weeks 26 or 44 were randomized to IngMeb (n = 134) or vehicle (n = 69). IngMeb achieved a higher complete clearance rate than vehicle 8 weeks after randomization in AKs present at 8 weeks (46·7% vs. 18·4%; P < 0·01) and in emergent AKs (59·5% vs. 25·0%; P = 0·01). Based on those who completed 12 months of follow-up (n = 340), the overall 12-month clearance rate was estimated at 50·0%. Follow-up IngMeb treatment was well tolerated.This study demonstrated the long-term benefit of IngMeb 0·015% gel for initial and follow-up therapy of AKs.
Characterization of two polymorphic sites in the human kinin B1 receptor gene
Authors: D R Bachvarov, M Landry, I Pelletier, M Chevrette, C Betard, I Houde, J Bergeron, M Lebel, F Marceau
Journal: Journal of the American Society of Nephrology (1998)

On the basis of the genomic structure of the human B1 receptor (B1R) for kinins, the presence of possible allelic polymorphisms of this gene was investigated using restriction fragment-length polymorphism and single-strand conformation polymorphism. The frequencies of the found alleles were determined in healthy volunteers and in patients with a history of end-stage renal failure, because there is evidence for a nephroprotective action of the kallikrein-kinin system. An A1098-->G polymorphism has been identified in exon 3 in a minority of volunteer blood donors, and is located 35 nucleotides downstream from the stop codon and 14 nucleotides upstream from the polyadenylation signal. The frequency of the G allele is 4.4% in the control sample and not significantly altered in patients with a history of end-stage renal failure. A second and more frequent polymorphism (18.1% of the alleles in the control group, prevalence of 33.3%) consists of a single base substitution (G-699-->C) in the putative promoter region. This polymorphism is significantly less frequent in the population of renal failure patients (prevalence of 20.6%) and determines an increased activity of the promoter function in constructions involving a reporter gene. The altered prevalence of this allele was also found in some etiologic subgroups of uremic patients. This study confirms the mapping of the B1R gene to 14q32. Other investigators have mapped the bradykinin B2 receptor (B2R) gene to a close site on human chromosome 14. A previously described B2R polymorphism (exon 2, C181-->T) had an allele frequency of 9.7% in the control sample and appears to be clinically neutral. The polymorphism of the B1R promoter may be a marker of prognostic significance for the preservation of renal function in diseased individuals.