tbuckley/cabot-search huggingface dataset:
Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis
Authors: Xiaojie Xu, Zhongyi Fan, Lei Kang, Juqiang Han, Chengying Jiang, Xiaofei Zheng, Ziman Zhu, Huabo Jiao, Jing Lin, Kai Jiang, Lihua Ding, Hao Zhang, Long Cheng, Hanjiang Fu, Yi Song, Ying Jiang, Jiahong Liu, Rongfu Wang, Nan Du, Qinong Ye
Journal: Journal of Clinical Investigation (2013)

MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover, expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment.
Migraine: Intelligence, Social Class, and Familial Prevalence
Authors: W. E. Waters
Journal: BMJ (1971)

Groups of individuals with headache, unilateral headache, and migraine, and a fourth group who had not had a headache in the previous year, were identified by questionnaire from a random sample of adults in the general population. Intelligence and social class were assessed in about 400 individuals. There was no evidence that individuals with migraine were more intelligent or of higher social class. There was, however, a suggestion that the more intelligent individuals with migraine, and those in social classes I and II, were more likely to consult a doctor for their headaches. This trend might explain the origin of the hypotheses associating migraine with intelligence and with social class. Random samples of individuals with migraine with headache and without headache in the previous year were the probands for a family study. There were 524 first-degree relatives over 21 years of age who lived in South Wales. Headache histories, obtained "blindly" from over 99% of these relatives with a standard questionnaire, were classified as migraine, possible migraine, headache, or without headache in the previous year. The prevalence of migraine in the families of the migrainous probands was nearly twice as high as the prevalence in the other families, but this difference was not statistically significant. It is suggested that family history should not be included in the definition of migraine and that heredity is much less important in migraine than is usually supposed.
A new paradigm for classification of disease severity and progression of COPD
Authors: David Mannino, Enrique Diaz-Guzman, John Pospisil
Journal: European Respiratory Journal (2012)

Background: The current classification scheme for COPD uses lung function to classify disease severity and monitor disease progression. This scheme does not capture other important components of the disease process, nor does it allow for improvement of disease status.  Methods: We evaluated existing data to develop a classification scheme for COPD using measures beyond lung function, including respiratory symptoms, exacerbation history, quality of life assessment, comorbidity, and body mass index. We then applied this classification to data from the Lung Health Study, calculating a score for study subjects in year 1 and year 5 of the study, along with the difference between year 1 and year 5.  Results: We developed a 4 point scale ranging from 1.00 (mild) to 4.00 (very severe). In year 1 of the study, the mean COPD score was 1.76 (standard deviation [SD] 0.35), in year 5 it was 1.82 (SD 0.38). The mean difference from year 1 to year 5 was an increase (worsening) of 0.06 (SD 0.37), and a range from -1.0 to 1.6. The COPD score at year 1, year 5, and the difference between these scores were all predictive of mortality at follow-up. For example, the 14.0% of subjects whose score improved by at least 0.25 between year 1 and 5 had decreased mortality compared to those with stable scores (between -0.25 and 0.25, hazard ratio 0.6, 95% confidence interval 0.4, 0.8). Conversely, those whose score worsened by 0.75 or more points had increased mortality (HR 1.7, 95% CI 1.2, 2.5).  Conclusions: A COPD score that includes components in addition to lung function and allows for both improvement and worsening of disease may provide additional guidance to COPD classification, management, and prognosis.
Indoor levels of fungal spores in Central Florida homes without obvious moisture problems
Authors: P.J. DeMarco, R. Codina, A.S. Bagg, R.W. Fox, R.F. Lockey
Journal: Journal of Allergy and Clinical Immunology (2005)

RATIONALE: This is a pilot study to determine types and levels of airborne fungal spores during the summer of 2004 in homes located in central Florida. METHODS: Eighteen single-family homes were selected based on protocol questionnaire and cursory inspection, which revealed no obvious moisture or visible fungal contamination. Fungal spores were collected by non-culturable sampling utilizing Air-O-Cell cassettesTM. Three indoor samples and two outdoor samples were collected from each home. One indoor and two outdoor samples were not interpretable. Fifty-three indoor air samples (IAS) and 34 outdoor air samples (OAS) were analyzed by optical microscopy. Non-parametric statistical analysis was performed. RESULTS: Total counts (TS) in spores/m3 detected in OAS ranged from 468 to 333,538 (median = 2,355). TS detected in IAS ranged from 8 to 999 (median = 335), resulting in relative percents compared to OAS ranging from 0.06 % to 61.5 % (median = 11.0%). The most prevalent spore types in OAS were Ascospores (range: 123-176,000, median = 688; median of % outdoor TS = 32.3%) and Basidiospores (range: 70-156,992, median = 726; median of % outdoor TS = 24.7%). The most prevalent spore types in IAS were Penicillium and Aspergillus (range: 0-656, median = 194; median of % indoor TS = 52.0%; median of % IAS compared to OAS = 77.8%). CONCLUSIONS: Airborne fungal spores are present in homes without moisture problems during the summer in central Florida. Additional studies during different seasons and in different geographical locations are needed to determine standard reference levels and types of indoor airborne fungal spores.
Acute leg ischaemia
Authors: S. Brearley
Journal: BMJ (2013)

A 55 year old man consulted his general practitioner complaining of persistent pain in his left leg for three days and a numb feeling in the foot. He was taking treatment for hypertension, had a history of low back pain, and was a smoker of 20 cigarettes a day. His foot looked normal, but sensation seemed mildly reduced. The general practitioner noted a weak dorsalis pedis pulse. A diagnosis of sciatica was made, diclofenac was prescribed, and the patient was invited to return a week later if no better. Six days later he presented to a local emergency department because of intolerable pain and was found to have a profoundly ischaemic left leg necessitating an above knee amputation.

Missed diagnoses of acute leg ischaemia, as in the case above, are common.1 2 An analysis of data held by the NHS Litigation Authority (NHSLA), the Medical Defence Union (MDU), and the Medical Protection Society (MPS) identified 224 cases of acute leg ischaemia leading to limb loss over a 10 year period,1 in all of which litigation had been initiated. Fifty one cases in which there had been delay in detecting and treating acute limb ischaemia were reported to the National Reporting and Learning System (NRLS) between 2003 and 2010.2 I have written almost 30 medicolegal reports on cases in which there were allegations—usually against general practitioners or casualty officers—of a negligent delay in diagnosing acute leg ischaemia, often resulting in the avoidable loss of a limb. 

Leg ischaemia results from thrombotic, embolic, or traumatic arterial occlusion. It is considered to be acute if the symptoms and signs have developed over less than two weeks.3 4 The …
Angiogenesis-Promoting Gene Patterns in Alveolar Soft Part Sarcoma
Authors: Alexander J.F. Lazar, Parimal Das, Daniel Tuvin, Borys Korchin, Quansheng Zhu, Zeming Jin, Carla L. Warneke, Peter S. Zhang, Vivian Hernandez, Dolores Lopez-Terrada, Peter W. Pisters, Raphael E. Pollock, Dina Lev
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We examined a cohort of patients with alveolar soft part sarcoma (ASPS) treated at our institution and showed the characteristic ASPSCR1-TFE3 fusion transcript in their tumors. Investigation of potential angiogenesis-modulating molecular determinants provided mechanistic and potentially therapeutically relevant insight into the enhanced vascularity characteristic of this unusual tumor. Experimental Design: Medical records of 71 patients with ASPS presenting at the University of Texas M.D. Anderson Cancer Center (1986-2005) were reviewed to isolate 33 patients with formalin-fixed paraffin-embedded material available for study. RNA extracted from available fresh-frozen and formalin-fixed paraffin-embedded human ASPS tumors were analyzed for ASPSCR1-TFE3 fusion transcript expression using reverse transcription-PCR and by angiogenesis oligomicroarrays with immunohistochemical confirmation. Results: Similar to previous studies, actuarial 5- and 10-year survival rates were 74% and 51%, respectively, despite frequent metastasis. ASPSCR1-TFE3 fusion transcripts were identified in 16 of 18 ASPS samples. In the three frozen samples subjected to an angiogenesis oligoarray, 18 angiogenesis-related genes were up-regulated in tumor over adjacent normal tissue. Immunohistochemistry for jag-1, midkine, and angiogenin in 33 human ASPS samples confirmed these results. Comparison with other sarcomas indicates that the ASPS angiogenic signature is unique. Conclusion: ASPS is a highly vascular and metastatic tumor with a surprisingly favorable outcome; therapeutically resistant metastases drive mortality. Future molecular therapies targeting overexpressed angiogenesis-promoting proteins (such as those identified here) could benefit patients with ASPS.
Blood Glucose Control in Type 1 Diabetes With a Bihormonal Bionic Endocrine Pancreas
Authors: Steven J. Russell, Firas H. El-Khatib, David M. Nathan, Kendra L. Magyar, John Jiang, Edward R. Damiano
Journal: Diabetes Care (2012)

OBJECTIVE To test whether safe and effective glycemic control could be achieved in type 1 diabetes using a bihormonal bionic endocrine pancreas driven by a continuous glucose monitor in experiments lasting more than two days and including six high-carbohydrate meals and exercise as challenges to glycemic control. RESEARCH DESIGN AND METHODS Six subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. Blood glucose was managed with a bionic endocrine pancreas controlling subcutaneous delivery of insulin and glucagon with insulin pumps. A partial meal-priming bolus of insulin (0.035 units/kg/meal, then 0.05 units/kg/meal in repeat experiments) was administered at the beginning of each meal (on average 78 ± 12 g of carbohydrates per meal were consumed). Plasma glucose (PG) control was evaluated with a reference quality measurement on venous blood every 15 min. RESULTS The overall mean PG was 158 mg/dL, with 68% of PG values in the range of 70–180 mg/dL. There were no significant differences in mean PG between larger and smaller meal-priming bolus experiments. Hypoglycemia (PG &amp;lt;70 mg/dL) was rare, with eight incidents during 576 h of closed-loop control (0.7% of total time). During 192 h of nighttime control, mean PG was 123 mg/dL, with 93% of PG values in the range of 70–180 mg/dL and only one episode of mild hypoglycemia (minimum PG 62 mg/dL). CONCLUSIONS A bihormonal bionic endocrine pancreas achieved excellent glycemic control with minimal hypoglycemia over the course of two days of continuous use despite high-carbohydrate meals and exercise. A trial testing a wearable version of the system under free-living conditions is justified.
Evaluation in man of fenclozic acid (I.C.I. 54,450: Myalex), a new anti-inflammatory agent. I. Serum concentration studies in healthy individuals and in patients with rheumatoid arthritis.
Authors: T M Chalmers, J E Pohl, D S Platt
Journal: Annals of the Rheumatic Diseases (1969)

<h3>Abstract</h3> Plasma membranes dynamically respond to external cues and changing environment. Quantitative measurements of these adaptations can elucidate the mechanism that cells exploit to survive, adapt and function. However, cell-based assays are affected by active processes while measurements on synthetic models suffer from compositional limitations. Here, as a model system we employ giant plasma membrane vesicles (GPMVs), which largely preserve the plasma membrane lipidome and proteome. From analysis of fluorescence emission and lifetime of environment-sensitive dyes, and membrane shape fluctuations, we investigate how plasma membrane order, viscosity and bending rigidity are affected by different stimuli such as cell seeding density in three different cell models. Our studies reveal that bending rigidity of plasma membranes vary with lipid order and microviscosity in a highly correlated fashion. Thus, readouts from polarity- and viscosity-sensitive probes represent a promising indicator of membrane mechanical properties. Quantitative analysis of the data allows for comparison to synthetic lipid membranes as plasma membrane mimetics.
Localised pulmonary metastatic calcification associated with pulmonary artery obstruction.
Authors: J Bloodworth, J F Tomashefski
Journal: Thorax (1992)

BACKGROUND: Metastatic pulmonary calcification, a complication of uraemia and disordered calcium metabolism, may be diffuse or localised. The factors that determine calcium precipitation are complex, but tissue alkalosis is thought to be important. As obstruction of the pulmonary artery theoretically causes local alkalosis a retrospective necropsy study was carried out to examine the relation between metastatic pulmonary calcification and vascular obstruction. METHODS: Five patients with focal and two with diffuse metastatic calcification in the lungs were identified over eight years. Lungs were studied macroscopically and by light microscopy, haematoxylin and eosin and histochemical stains being used for calcium. RESULTS: Underlying risk factors for calcification in these patients included renal failure in six and disseminated malignancy in five. In the five patients with localised calcification obstruction of the pulmonary artery by thrombus or tumour was found proximal or adjacent to areas of calcium deposition. In two patients metastatic calcification was confined to a lung with unilateral pulmonary artery thromboembolic occlusion. Calcification was not specifically associated with infarction, pneumonia, or diffuse alveolar damage. Lesions of the pulmonary artery were not seen in the two patients with diffuse bilateral metastatic calcification. CONCLUSION: In this small series there was a spatial association between pulmonary artery obstruction and localised metastatic calcification. It is proposed that pulmonary artery obstruction alters the microchemical environment of the lung, favouring tissue alkalosis and thereby enhancing parenchymal calcification in patients predisposed to this condition.
An intervention to decrease complications related to endotracheal intubation in the intensive care unit: a prospective, multiple-center study
Authors: Samir Jaber, Boris Jung, Philippe Corne, Mustapha Sebbane, Laurent Muller, Gerald Chanques, Daniel Verzilli, Olivier Jonquet, Jean-Jacques Eledjam, Jean-Yves Lefrant
Journal: Intensive Care Medicine (2009)
Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection
Authors: H Nakamura, S Fujishima, T Inoue, Y Ohkubo, K Soejima, Y Waki, M Mori, T Urano, F Sakamaki, S Tasaka, A Ishizaka, M Kanazawa, K Yamaguchi
Journal: European Respiratory Journal (1999)

The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p&lt;0.05), vital capacity (VC) (p&lt;0.001), %VC (p&lt;0.05) and forced expiratory volume in one second (p&lt;0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p&lt;0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.
Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells
Authors: Chen Wang, Tai Yi, Lingfeng Qin, Roberto A. Maldonado, Ulrich H. von Andrian, Sanjay Kulkarni, George Tellides, Jordan S. Pober
Journal: Journal of Clinical Investigation (2013)

Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4+ memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4+ memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4+CD25hiCD127loFoxP3+ cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection.
Intraindividual response to treatment with pirfenidone in two independent European IPF cohorts
Authors: Benjamin Loeh, Fotios Drakopanagiotakis, Gian Pierro Bandelli, Elisa Cordani, Silke Tello, Daniel von der Beck, Werner Seeger, Philipp Markart, Andreas Guenther, Carlo Albera
Journal: European Respiratory Journal (2014)

Background

Pirfenidone is an anti-fibrotic drug that has been approved for the treatment of patients with mild /moderate idiopathic pulmonary fibrosis (IPF).

Methods

Clinical data from 197 IPF patients (113 from Turin, 84 from Giessen) prior and after initiation of pirfenidone treatment: a retrospective analysis was conducted following an “intention to treat” (ITT, no selection bias, all PFTs from all patients) and a “per protocol” (PP, only pats with > 3 PFTs prior and after pirfenidone) approach.

Results

The study population had the following characteristics prior to treatment: mean age 69,90 (SD 7,95) years, 71% males, mean FVC 2,3 (SD 0,8) liters, corresponding to a predicted FVC (FVC%) of 64,98 (SD 18,81), mean % predicted of DLCO (DLCO%) 39,79 (SD 17). In the “ITT” approach, pirfenidone treatment was associated with a significant reversal of the annual decline rate of FVC% in the Turin (p<0,001), Giessen (p=0,0329) and the entire cohort (p<0,001). In the “PP” approach, pirfenidone treatment was also associated with a significant attenuation of the annual decline in FVC and DLCO (table 1). Intraindividual analysis, however, also revealed that a minor fraction of patients did not respond to pirfenidone at all.

View this table:



Implications

Most IPF patients responded to pirfenidone , resulting in stabilized or even improved PFT values. However, some patients completely failed to respond.Development of individualized treatment algorithms is warranted.
"Systematic review" of asthma education studies
Authors: G. DOUGLAS
Journal: Thorax (2000)

The spectrum of nitrofurantoin lung injury continues to widen.The case histories are presented of two patients who developed lung disease associated with the use of nitrofurantoin with histological features of bronchiolitis obliterans organising pneumonia (BOOP), a rare but recognised form of drug induced injury.The two middle aged women presented with respiratory symptoms after prolonged treatment with nitrofurantoin.Both had impaired lung function and abnormal computed tomographic scans, and their condition improved when nitrofurantoin was withdrawn and corticosteroid treatment commenced.The favourable outcome in these two patients contrasts with the fatal outcome of the two other reported cases of nitrofurantoin induced BOOP.We suggest that the previous classification of nitrofurantoin induced lung injury into "acute" and "chronic" injury is an oversimplification in view of the wide variety of pathological entities that have subsequently emerged.
Food Allergies: Prevalence, Molecular Characterization, and Treatment/Prevention Strategies
Authors: Laurie A. Lee, A. Wesley Burks
Journal: Annual Review of Nutrition (2006)

A significant proportion of the population is either affected by or concerned about food allergy. Our knowledge about food allergens and how they stimulate the immune system has increased dramatically over the past decade. However, reasons for the increased prevalence of food allergy are not clear. The diagnosis of food allergy requires that the patient and caregivers examine all foods for the presence of potential allergens in order to prevent inadvertent ingestion and further reactions. Fortunately, many children develop tolerance to allergenic foods after a period of dietary elimination. Various immunotherapy approaches are under investigation to alleviate or prevent food-induced reactions in those who have persistent food allergies.