tbuckley/cabot-search huggingface dataset:
Stable lung function is maintained over 2 years in newborn screened (NBS) CF infants
Authors: Lena Priscilla Thia, Ah-Fong Hoo, Lucy Brennan, Jane Chudleigh, Angela Wade, Colin Wallis, Andrew Bush, Gary Ruiz, Caroline Pao, Janet Stocks
Journal: European Respiratory Journal (2013)

Background :Lung function in LCFC NBS CF infants was impaired by age 3-months (3m) compared to healthy controls. 1 However forced expiratory volume (FEV 0.5 ) improved by 1-year (1y) while lung clearance index (LCI) and plethysmographic functional residual capacity (FRC) remained stable. 2  These findings contrast with previous reports of progressive deterioration of lung function in NBS CF infants.  Hypothesis :In NBS CF infants, lung function is stable to 2y.  Methods :LCI, FRC and FEV 0.5  were measured in NBS CF infants and controls at 3m, 1y and 2y.  Results :To date, 50 CF and 24 control infants have completed 3 tests. Mildly elevated LCI and FRC remained stable from 3m-1y with no further deterioration by 2y. LCI and FRC were on average higher in CF whereas a significant reduction in FEV 0.5  was only evident at 3m. Longitudinal changes in LCI and FRC were similar in both groups; whilst significant improvement in FEV 0.5  for CF from 3m-1y was significantly different from the lack of change in controls.   Conclusions :This is the 1st study to demonstrate stable lung function to 2y in NBS CF infants managed on standard CF therapy. These results suggest that in these infants, novel treatments could be deferred beyond infancy when objective outcomes are more easily measured.  References : 1 Hoo  et al . Thorax 2012; 2 Thia  et al . ERJ 2011(S55).
Sensitive detection of major food allergens in breast milk: first gateway for allergenic contact during breastfeeding
Authors: C. Pastor‐Vargas, A. S. Maroto, A. Díaz‐Perales, M. Villaba, N. Casillas Diaz, F. Vivanco, J. Cuesta‐Herranz
Journal: Allergy (2015)

Food allergy is recognized as a major public health issue, especially in early childhood. It has been hypothesized that early sensitization to food allergens maybe due to their ingestion as components dissolved in the milk during the breastfeeding, explaining reaction to a food, which has never been taken before. Thus, the aim of this work has been to detect the presence of the food allergens in breast milk by microarray technology. We produced a homemade microarray with antibodies produced against major food allergens. The antibody microarray was incubated with breast milk from 14 women collected from Fundación Jiménez Díaz Hospital. In this way, we demonstrated the presence of major foods allergens in breast milk. The analysis of allergens presented in breast milk could be a useful tool in allergy prevention and could provide us a key data on the role of this feeding in tolerance induction or sensitization in children.
Pretreatment prognostic factors for survival in small-cell lung cancer: A new prognostic index and validation of three known prognostic indices on 341 patients
Authors: I. Maestu, M. Pastor, J. Gómez-Codina, J. Aparicio, A. Oltra, C. Herranz, J. Montalar, B. Munárriz, G. Reynés
Journal: Annals of Oncology (1997)
The influential T cell in B-cell neoplasms.
Authors: N E Kay, M M Oken, R T Perri
Journal: Journal of Clinical Oncology (1983)

Investigations of human B-cell malignancies have generally focused on the monoclonal B-cell populations. Until recently there has been little emphasis on the thymus (T) lymphocyte in these disorders. Current studies, however, suggest that quantitative and qualitative disorders of T cells are generally seen both in chronic lymphocytic leukemia and in multiple myeloma. This review will focus on two major concepts. First, it will define the quantitative and functional T-cell abnormalities in B-cell malignancies including evidence suggesting a causal link between the T-cell abnormalities and certain observed disease manifestations in chronic lymphocytic leukemia and multiple myeloma. Secondly, it will review data demonstrating that these T cells may be influenced by in vivo and in vitro manipulations and will outline some of the possible resultant clinical effects.
Targeted Ablation of the Murine α-Tropomyosin Gene
Authors: Edward M. Blanchard, Kenji Iizuka, Michael Christe, David A. Conner, Anja Geisterfer-Lowrance, Frederick J. Schoen, David W. Maughan, Christine E. Seidman, J.G. Seidman
Journal: Circulation Research (1997)

Abstract We created a mouse that lacks a functional α-tropomyosin gene using gene targeting in embryonic stem cells and blastocyst-mediated transgenesis. Homozygous α-tropomyosin “knockout” mice die between embryonic day 9.5 and 13.5 and lack α-tropomyosin mRNA. Heterozygous α-tropomyosin knockout mice have ≈50% as much cardiac α-tropomyosin mRNA as wild-type littermates but similar α-tropomyosin protein levels. Cardiac gross morphology, histology, and function (assessed by working heart preparations) of heterozygous α-tropomyosin knockout and wild-type mice were indistinguishable. Mechanical performance of skinned papillary muscle strips derived from mutant and wild-type hearts also revealed no differences. We conclude that haploinsufficiency of the α-tropomyosin gene produces little or no change in cardiac function or structure, whereas total α-tropomyosin deficiency is incompatible with life. These findings imply that in heterozygotes there is a regulatory mechanism that maintains the level of myofibrillar tropomyosin despite the reduction in α-tropomyosin mRNA.
Electron Microscopic Identification of Viral Particles in Calcifying Epithelioma Induced by Polyoma Virus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Ken Hashimoto, Lodewijk A. Magré, Walter F. Lever
Journal: JNCI Journal of the National Cancer Institute (1967)

Tumors similar to human calcifying epithelioma of Malherbe were induced in C3H/Bi mice byinoculation of polyoma virus. Histological and ultrastructural resemblance of these tumors to the human counterpart, including calcification of cortical cell type of tumor cells, was striking. Electron microscopically the so-called basophilic cells were premature cortical, cuticular, and inner root-sheath cells. Predominant, however, was the inner root-sheath cell (Huxley and Henle cells). Hyalinized and calcified certlccl cells, imbricate cuticular cells, and typical outer root-sheath cells were identified. Virus particles were found only in tumor cells with the differentiation. toward inner root-sheath cells. Visible viral particles first appeared in the nucleus where they were closely related to the nuclear chromatin, and, after proliferation in the nucleus,spread into the cytoplasm and eventually, with the destruction of the host cells, disappeared. Few extracellular viral particles were present. In the nucleus as well as in the cytoplasm they often formed crystalline arrays. Cylindrical viruses were also observed. An individual virus particle measured from 280–380 A and consisted of a dense body and light dots or rods/interpreted as capsomeres.
End pharmacists’ monopoly on selling certain drugs
Authors: Paul Rutter
Journal: BMJ (2015)

Evidence is lacking that oversight by pharmacists has benefits, writes Paul Rutter, who thinks that the US dichotomy of prescription-only and non-prescription drugs is simpler 1778In January 2015 the UK Medicines and Healthcare Products Regulatory Agency announced that oral diclofenac would no longer be available as a non-prescription drug sold exclusively under the direction of a pharmacist (a "pharmacy medicine").Instead, it would revert to prescription-only control because of a small but notably increased risk of cardiovascular side effects.[1]Despite oral diclofenac having previously been restricted to sale through pharmacies the UK regulator decided that risks could not be ruled out-even in short term use and at lower doses than those prescribed.This implies that, even with this system of restricted availability, doubt exists that pharmacists (and their staff) can supervise sales to consumers appropriately.Given this decision, should any drugs still be restricted to sale only with a pharmacist's supervision?Globally, many governments have healthcare policies that advocate for less prescription-only control of drugs.The mechanism for deregulation varies, but consumers worldwide can access drugs more easily than ever before.[2] Use of non-prescription drugs is the most prevalent form of medical care in the world, with a global market worth an estimated €73bn (£52bn; $82bn), and their sales growth now exceeds that of prescriptiononly drugs.[3]Many countries (including Australia, Canada, France, New Zealand, Sweden, and the United Kingdom) foster the declassification of drugs that are under prescription-only control by having a category of drugs that can be bought only at a pharmacy.These "pharmacy medicines" must be sold either by pharmacists or under their supervision.In the past 30 years this approach to reclassification has seen many therapeutic agents made available to consumers without a prescription, including proton pump inhibitors (in the United States and the European Union), orlistat (EU), triptans (UK and Germany), and β2 agonists (Singapore and Australia).
Abstract 307: Structural Characterization of Calcineurin A-Calsarcin 1 Assembly
Authors: Carlos R Koscky Paier, Alisson C Cardoso, Tatiani L Brenneli, Rodrigo V Honorato, Fábio C Gozzo, Paulo S Oliveira, Kleber G Franchini
Journal: Circulation Research (2014)

Signaling by the calcium-dependent phosphatase calcineurin (Cn) plays key roles in regulating cardiac development, hypertrophy, and pathological remodeling. Cn binds to and is negatively regulated by calsarcins (CS), a family of muscle-specific proteins. However, the molecular mechanisms involved in the inhibition of Cn by CS remain unclear. Understanding the architecture and structure of Cn-CS complex is critical to unravel the regulation of Cn by CS. Here we combined biochemical assays, chemical cross-linking coupled to mass spectrometry experiments (MS/MS), mutational analysis and a modeling strategy for structural characterization of CnA-CS1 assembly. The MS/MS data obtained from the cross-linked peptides of both proteins were used to guide an in silico docking of their polypeptide models. The protein complex models with the smallest estimated binding energy were clustered according to structural similarity and submitted to molecular dynamics simulation. The interacting surface of CnA was mapped in a pocket between the 1st and 3rd α-helixes and surrounding loops, while the corresponding surface of CS1 was mapped to the carboxyterminal loops within the Leu179-Phe185, Phe195-Ser199 and Thr250-Leu264 regions. Notably, the region of CnA that interacts with CS1 was found to be located in close proximity, but not coincident, to the β-sheet 14, the main binding site for the PxIxIT sequence of NFAT. Experiments performed with several CnA (FLAG-CnA) and CS1 (myc-CS1) mutants were used to validate the structural model of the CnA-CS1 assembly. The Lys40 (CnA) and Glu254 (CS1) residues were identified as critical for the complex stability. The model that emerges from this study supports the notion that CS1 interacts with an allosteric site to inhibit the activity of CnA. Alternatively, the close proximity of the CS1 to NFAT interacting site supports an interference of CS1 on the ability of CnA to bind and activate NFAT.
Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity
Authors: Shihyin Tsai, Joanna M. Sitzmann, Somasish G. Dastidar, Ariana A. Rodriguez, Stephanie L. Vu, Circe E. McDonald, Emmeline C. Academia, Monique N. O’Leary, Travis D. Ashe, Albert R. La Spada, Brian K. Kennedy
Journal: Journal of Clinical Investigation (2015)

Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) is a key downstream effector of mTOR complex 1 (mTORC1) that represses cap-dependent mRNA translation initiation by sequestering the translation initiation factor eIF4E. Reduced mTORC1 signaling is associated with life span extension and improved metabolic homeostasis, yet the downstream targets that mediate these benefits are unclear. Here, we demonstrated that enhanced 4E-BP1 activity in mouse skeletal muscle protects against age- and diet-induced insulin resistance and metabolic rate decline. Transgenic animals displayed increased energy expenditure; altered adipose tissue distribution, including reduced white adipose accumulation and preserved brown adipose mass; and were protected from hepatic steatosis. Skeletal muscle-specific 4E-BP1 mediated metabolic protection directly through increased translation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and enhanced respiratory function. Non-cell autonomous protection was through preservation of brown adipose tissue metabolism, which was increased in 4E-BP1 transgenic animals during normal aging and in a response to diet-induced type 2 diabetes. Adipose phenotypes may derive from enhanced skeletal muscle expression and secretion of the known myokine FGF21. Unlike skeletal muscle, enhanced adipose-specific 4E-BP1 activity was not protective but instead was deleterious in response to the same challenges. These findings indicate that regulation of 4E-BP1 in skeletal muscle may serve as an important conduit through which mTORC1 controls metabolism.
Nature and Rate of Neoplasia Found in Captive Wild Mammals, Birds, and Reptiles at Necropsy
Authors: Marc Effron, Lynn Griner, Kurt Benirschke
Journal: JNCI Journal of the National Cancer Institute (1977)

The nature and rate of neoplasia found at necropsy of captive wild animals of the Zoological Society of San Diego collection were studied. Neoplasia was present at necropsy in 2.75% of 3,127 mammals, 1.89% of 5,957 birds, and 2.19% of 1,233 reptiles. Neoplasms were not detected during 198 necropsies of amphibians. Gross and histologic examinations were performed on the 92 mammalian, 111 avian, and 28 reptilian neoplasms. The lesions were diagnosed. The findings findings included a high frequency of lymphosarcomas in birds and reptiles, multiple lung adenomas in mammals, multiple endocrine tumors in 2 European mouflons (Ovis musimon), and proliferative lesions of the biliary and pancreatic ductal systems in several species.
Intratumoral injection of tranexamic acid for control of biopsy-induced bleeding: Two years' experience of a new bronchoscopic technique
Authors: Adil Zamani
Journal: European Respiratory Journal (2012)

Background:  Significant bleeding may occur following forceps biopsy or brushing of necrotic or hypervascular tumors in the airways. In some cases, such methods as endobronchial instillation of iced saline lavage and epinephrine may fail to control the bleeding.   Objectives:  To describe and assess the efficacy of a new bronchoscopic technique using intratumoral injection of tranexamic acid (IIT) for control bleeding during biopsy procedure.   Method:  IIT was performed in those patients who had endoscopically visible tumoral lesions with continued active bleeding following the first attempt of bronchoscopic sampling (forceps biopsy or endobronchial needle aspiration). Tranexamic acid (TEA) in dose of 250-500 mg was injected through a 22-gauge Wang cytology needle (MW-122) into the lesion. After 2-3 minutes of waiting, multiple forceps biopsy specimens were obtained from the lesion.   Results:  Between Oct 2009 and Jan 2012, 14 male patients (mean age, 61 yrs; range, 41-80 yrs) underwent bronchoscopic IIT. Two patients with drug-eluting stents were on continuous dual antiplatelet therapy (aspirin plus clopidogrel). Multiple (3 to10; mean, 5.7) and deep biopsy specimens were obtained from the lesions without producing active bleeding. The following histopathologic diagnoses were made: squamous cell carcinoma (n=9), non-small cell lung cancer (n=3), and small cell carcinoma (n=2). There were no side effects observed with TEA.   Conclusion:  Bronchoscopic IIT is a useful and safe technique for controlling significant bleeding due to forceps biopsy procedure, and might be suggested as a prebiopsy injection for endobronchial necrotic or hypervascular tumors.
The utility of 18F-FDG PET/CT in chronic sarcoidosis
Authors: Jelica Videnovic-Ivanov, Dragana Sobic-Saranovic, Violeta Vucinic, Isidora Grozdic, Snezana Filipovic, Mihailo Stjepanovic, Maja Omcikus
Journal: European Respiratory Journal (2013)

The analysis was performed in chronic sarcoidosis patients with persistent clinical symptoms due to assess the utility of 18F-FDG PET/CT. The analysis were performed before and after the period of specific therapy for sarcoidosis due to clinical-radiographic-functional findings.  Methods: We analyzed 51 patients with chronic sarcoidosis (mean age ± SD: 47 ± 12 year; 38 F/13M). After the follow up (12 ± 5 months ), the clinical status,functional findings and therapy modalities were analyzed.  Results: 18F-FDG PET CT detected activity s.inflammation in 37 patients (82%) (SUV: 8.1 ± 3.9).MDCT was positive in 5 additional patients (89%). The difference between this two methods was not significant.Correlation between ACE levels and 18F-FDG PET/CT results were obtaine in 25 (49%) patients (P = 0.002,Mann–Whitney test). In 26 patients (51%) with positive 18F-FDG PET/CT findings, the ACE levels were in physiological levels. The therapies were initiated or even changed in 43 (81%). Significante correlation were find out between the positive 18F-FDG PET/CT results and changes in therapies. Conclusion: the results from our study indicate that 18F-FDG PET/CT is the important diagnostic method in chronic sarcoidosis due to obtaine the activity of sarcoidosis granulomas.
Therapeutic cancer vaccines
Authors: Cornelis J.M. Melief, Thorbald van Hall, Ramon Arens, Ferry Ossendorp, Sjoerd H. van der Burg
Journal: Journal of Clinical Investigation (2015)

The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies.
The Brain’s Response to Reward Anticipation and Depression in Adolescence: Dimensionality, Specificity, and Longitudinal Predictions in a Community-Based Sample
Authors: Argyris Stringaris, Pablo Vidal-Ribas Belil, Eric Artiges, Hervé Lemaitre, Fanny Gollier-Briant, Selina Wolke, Hélène Vulser, Ruben Miranda, Jani Penttilä, Maren Struve, Tahmine Fadai, Viola Kappel, Yvonne Grimmer, Robert Goodman, Luise Poustka, Patricia Conrod, Anna Cattrell, Tobias Banaschewski, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Herta Flor, Vincent Frouin, Juergen Gallinat, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Frauke Nees, Dimitri Papadopoulos, Tomas Paus, Michael N. Smolka, Henrik Walter, Rob Whelan, Jean-Luc Martinot, Gunter Schumann, Marie-Laure Paillère-Martinot
Journal: American Journal of Psychiatry (2015)

Objective: The authors examined whether alterations in the brain’s reward network operate as a mechanism across the spectrum of risk for depression. They then tested whether these alterations are specific to anhedonia as compared with low mood and whether they are predictive of depressive outcomes. Method: Functional MRI was used to collect blood-oxygen-level-dependent (BOLD) responses to anticipation of reward in the monetary incentive task in 1,576 adolescents in a community-based sample. Adolescents with current subthreshold depression and clinical depression were compared with matched healthy subjects. In addition, BOLD responses were compared across adolescents with anhedonia, low mood, or both symptoms, cross-sectionally and longitudinally. Results: Activity in the ventral striatum was reduced in participants with subthreshold and clinical depression relative to healthy comparison subjects. Low ventral striatum activation predicted transition to subthreshold or clinical depression in previously healthy adolescents at 2-year follow-up. Brain responses during reward anticipation decreased in a graded manner between healthy adolescents, adolescents with current or future subthreshold depression, and adolescents with current or future clinical depression. Low ventral striatum activity was associated with anhedonia but not low mood; however, the combined presence of both symptoms showed the strongest reductions in the ventral striatum in all analyses. Conclusions: The findings suggest that reduced striatal activation operates as a mechanism across the risk spectrum for depression. It is associated with anhedonia in healthy adolescents and is a behavioral indicator of positive valence systems, consistent with predictions based on the Research Domain Criteria.
High vs low-frequency neuromuscular electrical stimulation in COPD patients: What happens when current quantity is matched?
Authors: Audrey Fauge, François Alexandre, Emilie Tremey, Nicolas Oliver, Alain Varray, Nelly Heraud
Journal: European Respiratory Journal (2014)

If the clinical relevance of alternative techniques, such as neuromuscular electrical stimulation (NMES) seems justified in the management of severe COPD patients, no consensus on the parameters of stimulation are clearly given. A recent study showed that high frequencies [HF] increased more muscle strength than low frequencies [LF], but with higher delivered current quantity (same duration of session but higher number of pulses; Sillen et al. Thorax. 2014 0:1-7). We aim at comparing the effects on exercise tolerance and muscle function of two NMES programs [HF] vs [LF] when the quantity of current delivered is identical.  10 COPD patients admitted for pulmonary rehabilitation program (PR) were randomized in two groups: NMES-LF (25Hz, n=4) and NMES-HF (75Hz, n=6). The 2 programs were comparable for all stimulation parameters, excepted for the duration of session that was adjusted to ensure the same quantity of delivered current (LF=30min and HF=10min, 5x/week for 4 weeks). Exercise tolerance (6MWT) and quadriceps torque (Q MVC ) were evaluated before and after PR.  6MWT distance and Q MVC  increased significantly after NMES in both groups (p interaction  ranged from 0.48 to 0.9).  The results show that for equivalent amount of delivered current, improvement of exercise tolerance and Q MVC  are comparable. The differential effects observed in different programs of NMES thus depends more on the amount of current than the frequency used. Hence, when PR aiming at improving strength, HF may be preferentially proposed because of the shorter duration of session.