tbuckley/cabot-search huggingface dataset:
Enhanced expression of Robo4 ameliorates LPS-induced acute lung injury in mice
Authors: Xueling Wu, Yuanlin Song, Xiaodan Zhu, Xiaocong Fang, Chunxue Bai
Journal: European Respiratory Journal (2011)

The loss of endothelial integrity which causes leak of fluid and proteins into tissues contributes to the disease and death associated with acute lung injury. Slit2/Robo4 (an endothelium-specific) signaling promotes vascular stability. The purpose of this study was to evaluate the effect of enhanced expression of Robo4 on LPS-induced acute lung injury. We constructed a recombinant adenoviral vector expressing murine Robo4 (Ad.mRobo4) which were administered intranasally to BALB/c mice. Forty-eight hours later, all the mice were administered a single dose of LPS via i.p. injection to induce acute lung injury. A second cohort of mice was followed for survival for 7 days. Administration of Ad.m Robo4 increased increased the expression of Robo4 in lung tissue, as determined by reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry. Enhanced expression of Robo4 in lung suppressed the inflammatory reaction to LPS, attenuated the lung pathological changes, significantly reduced vascular permeability and edema in the lung determined by albumin in bronchoalveolar lavage fluid and also improved the survival of mice. Our results demonstrate a novel function manner for slit2/Robo4 signaling. Slit2/Robo4 pathway work formerly mainly considered as ligand-dependently, it has now to be considered as a ligand-independently and thus could be an attractive adjuvant in the treatment of acute lung injury.
Brief Report: Granulocyte–Macrophage Colony‐Stimulating Factor Drives Monosodium Urate Monohydrate Crystal–Induced Inflammatory Macrophage Differentiation and NLRP3 Inflammasome Up‐Regulation in an In Vivo Mouse Model
Authors: Odette M. Shaw, Stefanie Steiger, Xiao Liu, John A. Hamilton, Jacquie L. Harper
Journal: Arthritis & Rheumatology (2014)

To determine the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the differentiation of inflammatory macrophages in an in vivo model of monosodium urate monohydrate (MSU) crystal-induced inflammation.C57BL/6J mice were treated with either clodronate liposomes to deplete peritoneal macrophages or GM-CSF antibody and were then challenged by intraperitoneal injection of MSU crystals. Peritoneal lavage fluid was collected, and cellular infiltration was determined by flow cytometry. Purified resident and MSU crystal-recruited monocyte/macrophages were stimulated ex vivo with MSU crystals. The interleukin-1β (IL-1β) levels in lavage fluids and ex vivo assay supernatants were measured. GM-CSF-derived and macrophage colony-stimulating factor (M-CSF)-derived macrophages were generated in vitro from bone marrow cells. Protein expression of IL-1β, caspase 1, NLRP3, and ASC by in vitro- and in vivo-generated monocyte/macrophages was analyzed by Western blotting.Depletion of resident macrophages lowered MSU crystal-induced IL-1β and GM-CSF levels in vivo as well as IL-1β production by MSU crystal-recruited monocytes stimulated ex vivo. GM-CSF neutralization in vivo decreased MSU crystal-induced IL-1β levels and neutrophil infiltration. MSU crystal-recruited monocyte/macrophages from GM-CSF-neutralized mice expressed lower levels of the macrophage marker CD115 and produced less IL-1β following ex vivo stimulation. These monocytes exhibited decreased expression of NLRP3, pro/active IL-1β, and pro/active caspase 1. In vitro-derived GM-CSF-differentiated macrophages expressed higher levels of NLRP3, pro/active IL-1β, and pro/active caspase 1 compared to M-CSF-differentiated macrophages.GM-CSF plays a key role in the differentiation of MSU crystal-recruited monocytes into proinflammatory macrophages. GM-CSF production may therefore contribute to the exacerbation of inflammation in gout.
Early Gestational Intra-Amniotic Endotoxin
Authors: TIMOTHY J. M. MOSS, JOHN P. NEWNHAM, KAREN E. WILLETT, BORIS W. KRAMER, ALAN H. JOBE, MACHIKO IKEGAMI
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

We determined the effects in preterm lambs of endotoxin-induced inflammation at early gestational ages on lung function and structure and on the surfactant system. Pregnant ewes were randomized to one of five intra-amniotic endotoxin (Escherichia coli 055:B5) groups: 1 mg injected at 60 days of gestation, 1 mg at 80 days, 1 mg at 100 days, 1 mg at 60 days plus 100 days, or 0.6 mg/ day infused from Day 80 to Day 108. Control lambs received saline treatments. At 125 days, lung function was improved in all endotoxin groups. Marked increases in saturated phosphatidylcholine in lung tissue but not alveolar lavage samples were seen in all endotoxin groups except the 60- plus 100-day group. Surfactant protein mRNA and protein pool sizes were affected differently according to the timing of endotoxin treatment, but a large increase in the amount of mature surfactant protein B in alveolar lavage samples was observed in all endotoxin groups. Lung-to-body weight ratio, alveolar number, total surface area, and alveolar wall thickness were reduced by 80- to 108-day endotoxin. Intra-amniotic inflammatory stimuli in early gestation can alter pulmonary development, with the net effect of improving preterm lung function, despite changes in surfactant and lung growth that are similar to changes in the lungs of ventilated animals developing bronchopulmonary dysplasia.
FcγR and CR on blood monocytes in differentiation between sarcoidosis and tuberculosis
Authors: Anna Dubaniewicz, Marta Szadurska, Monika Wybieralska, Katarzyna Rogoza, Jan M. Slominski, Piotr Kmiec, Piotr Trzonkowski, Adam Sternau
Journal: European Respiratory Journal (2012)

Genetically different patients with sarcoidosis (SA) and tuberculosis (TB) induce dissimilar immune responses to the same mycobacterial heat shock proteins, which are implicated in forming of immune complexes (CIs). The complexemia in both diseases may result from a different function disorder of receptors for Fc of immunoglobulin G (FcγR) and complement receptors (CR) on monocytes in the phagocytosis and clearance of CIs with following persistent antigenemia and granuloma formation. Therefore, we analyzed the occurrence of FcγRI, FcγRII, FcγRIII and CR1, CR3, CR4 on blood CD14+ monocytes in 24 SA patients, 20 TB patients and 20 healthy volunteers using flow cytometry. Our results revealed significantly increased monocytes' presence with FcγRI-III and decreased with CR1 and CR4 in SA than controls. Analysis of monocytes' phenotypes revealed increased FcγRIII+CR1- and decreased FcγRII-CR1, FcγRII-CR3+, FcγRII-CR4+ occurrence in SA vs controls. In TB, higher presence of monocytes with particular FcγRI+, FcγRII+, CR1+ and CR3+ than in controls was detected. In SA vs TB, the occurrence of monocytes with FcγRIII+ receptor was significantly higher and with CR1+ was less frequent. The monocytes' phenotype FcγRIII+CR1- was increased in SA vs TB. In summary, there are increased frequencies of FcγRI+ and FcγRII+ monocytes in both SA and TB but in contrast to TB, sarcoid monocytes had increased FcγRIII occurrence with CR1 and CR4 deficiency. In SA, increased FcγR presence but CR deficiency on surface of blood monocytes may explain persistent antigenemia and complexemia in our patients with SA. This study may be useful for differentiation of both diseases.
Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.
Authors: I F Khouri, M Keating, M Körbling, D Przepiorka, P Anderlini, S O'Brien, S Giralt, C Ippoliti, B von Wolff, J Gajewski, M Donato, D Claxton, N Ueno, B Andersson, A Gee, R Champlin
Journal: Journal of Clinical Oncology (1998)

PURPOSE To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma. PATIENTS AND METHODS Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present. RESULTS Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04). CONCLUSION These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.
Impartial information about alcohol during pregnancy or another modern day witch hunt?
Authors: Alain Braillon, Susan Bewley
Journal: BMJ (2015)

O’Brien rightly rejects bullying intelligent, autonomous, adults just because they are pregnant.1 The answer to his question “just how common are fetal alcohol spectrum disorders?” is that alcohol during pregnancy is the foremost cause of preventable mental impairment in Western countries.2 Moreover, because few clinicians diagnose prenatal exposure to alcohol at birth, it is too late to offer secondary …
Abediterol, a novel long-acting inhaled β2-agonist, has a fast association rate and long residence time at human β2 receptors
Authors: Montserrat Miralpeix, María Letosa, Mónica Aparici, Carlos Puig, Amadeu Gavaldà, Dolors Vilella, Israel Ramos
Journal: European Respiratory Journal (2014)

Background   Abediterol (LAS100977) is a novel, long-acting, inhaled β 2 -receptor agonist (LABA) in Phase II development for treatment of asthma and COPD. We assessed abediterol binding kinetics vs reference LABAs indacaterol, olodaterol, vilanterol and salmeterol.   Methods   Binding assays were conducted using Sf9 cell membranes expressing human β 1  or β 2  adrenergic receptors. Dissociation was indirectly estimated by measuring  3 H-CGP12177 binding to LABA-occupied receptors. The β 2  receptor association/dissociation profiles and residence time were also determined directly using radiolabeled abediterol.   Results   Abediterol shows fast β 2  receptor association (K on  1.4x10 7 ±1.8x10 6  M -1 min -1 ) and a long residence time (t ½  1.5±0.2 h [measured directly] and 3.1±0.3 h [measured indirectly]). Abediterol is kinetically selective for human β 2  receptors (β 2 /β 1  dissociation ratio=77). Abediterol affinity (K off /K on ; 0.6 nM) correlates well with those reported in the literature. The β 2 -receptor dissociation rate of abediterol is 30–64 times slower than for reference LABAs (Table).   Conclusion   Abediterol has a fast association rate and a long residence time at β 2  receptors, and dissociates more slowly than reference LABAs. Abediterol is highly selective for β 2  vs β 1  receptors. These data support the long duration of action and favourable cardiovascular safety profile of abediterol seen in humans.
Transbronchial lung biopsy after lung transplantation: Different A and B scores in different lobes
Authors: Peter Jaksch, Axel Scheed, Silvana Geleff, Gerhard Dekan, Walter Klepetko
Journal: European Respiratory Journal (2011)

Background:  The use of transbronchial lung biopsy to monitor and diagnose acute cellular rejection in the lung allograft is a routine procedure in most TX centres. There is consensus in the minimum number of specimens being obtained and mostly biopsies are taken from more than one lobe.  Are there differences in rejection grading at different anatomic sites?  We examined our clinical data from the last 10 years to investigate the distribution of rejection grading of the lung allograft monitored by TBLB.   Methods:  A retrospective study was done reviewing the pathology files and slides of TBLB performed on lung allograft recipients. In 99 patients 298 transbronchial biopsies were taken from more than one lobe and were histologically graded following ISHLT guidelines. Corresponding B scores were just available in 207 investigated cases.   Results:  A-scores with identical grades were seen in 252 of 298 (85%) specimens, a single-grade difference was noted in 43 of 298 (14%) probes. Three cases demonstrated two grade differences on biopsies taken from two separate lobes (higher grade in the lower lobe).  B-scores were identical in 160 of 207 (77%) specimens, a single-grade difference was noted in 45 of 207 (21%) cases. Two cases demonstrated 2 grade difference (higher grade in the lower lobe).  Among cases with different grades of A and B scores, the “lower” lobes had a higher A grade in 55% (24/46) and a higher B grade in 59% (28/47).  Type of TX or underlying disease had no influence on the distribution of histological grading.   Conclusions:  If limitations on the site for transbronchial biopsy exist, biopsies of the lower lobes appear more informative.
Why do women use tobacco? A cross sectional survey from a developing country
Authors: Muhammad Irfan, Nashmia Riaz, Zubaida Sirang, Ahmed Suleman Haque, Javaid Ahmed Khan, Sheeba Shaikh
Journal: European Respiratory Journal (2013)

BACKGROUND:  In Pakistan the prevalence of smoking among young women has increased to 16.3%. There is a rapid increase in both use of smoking and smokeless tobacco over the decades. This has led to a rapid rise in lung diseases among women.  OBJECTIVE:  To determine the reasons of increasing tobacco use among women in Pakistan even after knowing of its countless hazards.  METHOD:  A cross-sectional survey was done on 490 females of aged 15 - 80 years. Questionnaire for tobacco use, developed by WHO, was used in both English and Urdu. Analysis was done using SPSS version 15.  RESULTS:  Out of 460 women, 13(3%) were current smokers and 79(17.6%) were smokeless tobacco users. 102(22.2%) had used tobacco for more than 6 months in some form. 98% of tobacco users were married, 82% were housewives and 76% were uneducated. 72% women used it for enjoyment, 69% for fear of withdrawal symptoms, 53% in social gatherings, 50% for relaxation, 45% as stress reliever. 25% of tobacco users considered tobacco use harmless and 51% thought its dangerous.  CONCLUSION:  Various factors were identified for the increase in tobacco use among women in Pakistan. Once started as a social activity not being able to stop for fear of withdrawal symptoms. Lack of knowledge of tobacco’s harmful effects also plays a major role. While targeting the masses for reduction of tobacco use it is essential that the reason for increase in tobacco be addressed in order to stop this epidemic.
Effect of Attention Training on Attention Bias Variability and PTSD Symptoms: Randomized Controlled Trials in Israeli and U.S. Combat Veterans
Authors: Amy S. Badura-Brack, Reut Naim, Tara J. Ryan, Ofir Levy, Rany Abend, Maya M. Khanna, Timothy J. McDermott, Daniel S. Pine, Yair Bar-Haim
Journal: American Journal of Psychiatry (2015)

Attention allocation to threat is perturbed in patients with posttraumatic stress disorder (PTSD), with some studies indicating excess attention to threat and others indicating fluctuations between threat vigilance and threat avoidance. The authors tested the efficacy of two alternative computerized protocols, attention bias modification and attention control training, for rectifying threat attendance patterns and reducing PTSD symptoms.
Standardized Intensive Care. Protocol Misalignment and Impact Misattribution
Authors: Brian P. Kavanagh, Michael Nurok
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<The ConceptsProtocol MisalignmentImpact MisattributionImplications for Legislat...Incorporating ProtocolsConclusionsReferencesCITING ARTICLES
Buzzwords in Dermatology
Authors: Rashi Minocha, Deshan F. Sebaratnam, James Young Joon Choi
Journal: JAMA Dermatology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Cancer Immunotherapy: More Is (Much) Better
Authors: Yosef Yarden, Michael Sela
Journal: Clinical Cancer Research (2015)

Although antibodies against EGFR and HER2 are used to treat cancer, only some patients respond and resistance often emerges. Jacobsen and colleagues present in this issue experimental evidence favoring replacement of the currently applied monoclonal antibodies with oligoclonal mixtures of six synergistic antibodies, simultaneously engaging EGFR, HER2, and also HER3.
Book: A History of Scottish Medicine
Authors: L. Weaver
Journal: BMJ (2003)

Helen M Dingwall Edinburgh University Press, £16.99, pp 282 www.eup.ed.ac.uk Rating: ![Graphic][1]</img>![Graphic][2]</img> ISBN 0 7486 0865 6 There are good reasons why Scottish medicine deserves a history. Scots physicians and surgeons feature prominently in the history of European medicine, and they and the medical schools and colleges that flourished in the 18th and 19th centuries were influential in shaping the modern medical profession. Our knowledge of medical history is largely of “great men” responsible for significant advances and discoveries. We are relatively ignorant of the social, political, and scientific context in which they lived and worked. This book aims “to account for the progress of Scottish medicine in the context of the evolution and … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
The sliding stop: a technique of fielding in cricket with a potential for serious knee injury: Figure 1
Authors: Konrad Von Hagen, Richard Roach, Bruce Summers
Journal: British Journal of Sports Medicine (2000)

The sliding stop method of fielding in cricket is gaining popularity in schools and club cricket through its frequent exposure on television. The case history is reported of a cricketer who suffered a torn medial meniscus in his knee, a rare cricketing injury, while performing this technique incorrectly in a club game. The correct method of performing the technique is described in coaching manuals but is not commonly instructed at club or school level. The sliding stop should be discouraged in school and for club cricketers unless appropriately coached.
The leukemia-associated RUNX1/ETO oncoprotein confers a mutator phenotype
Authors: V J Forster, M H Nahari, N Martinez-Soria, A K Bradburn, A Ptasinska, S A Assi, S E Fordham, H McNeil, C Bonifer, O Heidenreich, J M Allan
Journal: Leukemia (2015)

t(8;21) is a frequent chromosomal translocation in acute myeloid leukemia (AML) and is also reported in lymphoid and biphenotypic acute leukemia.1, 2 t(8;21) fuses the RUNX1 gene (AML1) on chromosome 21 to the ETO gene (RUNX1T1) on chromosome 8, encoding the RUNX1/ETO chimeric transcription factor that represses expression of RUNX1 target genes, promoting self-renewal and blocking myeloid differentiation.3, 4, 5, 6 t(8;21) is insufficient for leukemogenesis and additional co-operating mutations are required for transformation,7 including point mutations that activate and/or over express c-KIT.8 The mechanisms driving the acquisition of co-operating mutations remain unclear, although there is evidence that initiating lesions such as RUNX1/ETO may promote mutagenesis.9, 10 For example, ectopic expression of RUNX1/ETO downregulates several DNA-repair proteins (BRCA2, OGG1 and ATM) and increases the level of phosphorylated TP53 and γH2AX, indicating elevated DNA damage and a possible pro-mutagenic phenotype.10, 11
Lung resection in hematologic patients with pulmonary invasive fungal disease: Changing pattern in recent years
Authors: Christian Nebiker, Didier Lardinois, Lilian Junker, Franco Gambazzi, Joerg Halter, Jakob Passweg, Daiana Stolz, Maja Weisser, Lukas Bubendorf, Alois Gratwohl, Michael Tamm
Journal: European Respiratory Journal (2012)

Pulmonary invasive fungal disease (IFD) is a frequent complication in patients with hematologic malignancies. We analysed the outcome of 71 hematologic patients undergoing lung resection for suspected pulmonary IFD at a single centre and we compared patients operated before 2002 (group A n=41) with those undergoing surgery after 2002 (group B; n=30). Forty-four patients were neutropenic and 41 had a platelet count below 50 x 109/L. 45 non-anatomical resections and 26 lobectomies were performed. Fungal infection was histologically proven in 53 patients. Reoperation was needed in 4 cases: bronchial stump dehiscence, persistent air leak, chylothorax and seroma. Minor complications at the site of surgery occurred in 14 cases. In only two cases there was an uncontrolled disseminated fungal infection. Overall mortality at 30 days was 7% (5/71. The age was significantly higher (group B 40y versus group A 49y, p=0.0239) in the recently operated patients and a significant difference in ASA score (score III/IV 17% in group A versus 90% in group B, p   Conclusion:    Lung resection is a therapeutic option for hematological patients suffering from pulmonary fungal infection with an acceptable morbidity and mortality. In recent years patients were older, sicker, VATS was performed more often and in a considerable number of cases rare fungi could be detected.