tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: α-1 antitrypsin activates protein phosphatase 2A (PP2A) to counter lung inflammatory responses
Authors: Patrick Geraghty, Edward Eden, Manju Pillai, Michael Campos, Noel McElvaney, Robert Foronjy
Journal: European Respiratory Journal (2014)

This study investigated whether α-1 antitrypsin (A1AT) acts via protein phosphatase 2A (PP2A), a key serine threonine phosphatase, to alter TNF signaling, inflammation and proteolytic responses in the lung. PP2A activity was measured in peripheral blood neutrophils from A1AT deficient (PiZZ) and healthy (PiMM) individuals. PP2A activation was assessed in human neutrophils, airway epithelial cells and peripheral blood monocytes treated with plasma purified A1AT protein. PP2A was silenced in lung epithelial cells treated with A1AT and MMP and cytokine production was then measured following TNF-α stimulation. We found that neutrophils from PiZZ subjects had significantly lower PP2A activity. A1AT activated PP2A in several cell types in the lung.

![Figure][1] 



Moreover, A1AT acted via PP2A to prevent p38 and IκBα phosphorylation in TNF-α stimulated epithelial cells.

![Figure][1] 



In addition, A1AT modulated PP2A activity to counter MMP and cytokine expression triggered by TNF signaling in the lung. Thus, these findings establish for the first time that A1AT acts via PP2A to exert potent anti-inflammatory effects in the lung.

 [1]: pending:yes
Influence of in vivo prednisolone on increased in vitro O2-generation by neutrophils in emphysema
Authors: CL Jones, D Burnett, RA Stockley
Journal: European Respiratory Journal (1993)

<h3>Background</h3> In the UK, Sickle cell disease (SCD) affects 1 in 2,400 live births and there is now a nationwide screening programme in place. There are currently estimated to be 12,500 individuals living with SCD in England where it is the most common and fastest growing genetic disorder. Treatment is aimed at reducing complications with preventative measures such as prophylactic antibiotics, immunisation, and cranial doppler ultrasound to assess stroke risk. <h3>Objectives</h3> This audit aims to compare local outcomes at the North Middlesex University Hospital with the recommended national standards for the management of sickle cell disease. This poster presents the results of 2 years of audit data (a full audit cycle) to assess whether recommendations made in 2009 have led to improvements in outcomes in 2010. <h3>Methods</h3> Information was retrieved via a retrospective database and notes audit of 249 patients on the haemoglobinopathy register at North Middlesex Hospital. Collated data was compared to national standards. <h3>Results</h3> The UK national standards for sickle cell disease, taken from 3 government documents (see references), were audited on 2 consecutive years. There are 13 national standards on the treatment and management of pediatric sickle cell disease covering recommendations for newborn screening, penicillin and pneumococcal prophylaxis, transcranial doppler ultrasound (TCD) scanning and annual review. Out of 13 national targets, 6 were met in 2009 and 9 were met in 2010. Patient non attendance appointments led to a number of standards not being met in both years. <h3>Conclusions</h3> Improvement in meeting national targets occurred between 2009 and 2010 as a result of the audit process and subsequent recommendations such as changes to note keeping, the introduction of patient held records, family clinics, and the introduction of after school appointments for adolescents. The audit process itself highlighted issues such as patient non attendance and its impact on meeting standards. Non attendance remains a costly and troubling problem to the NHS where there has been a great impetus to look at the cost analysis of providing services. Steps are now being taken to reduce non attendance including a research project examining the correlation between social factors and non attendance.
The Printed Pill
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A novel approach to preventing adolescent smoking in schools
Authors: N Varun
Journal: Thorax (2008)

Addiction can occur rapidly in young smokers with consequent health problems in later life. Valuable resources are wasted when school interventions are ineffective, underscoring the need for evidence-based interventions. Approaches are often school-based owing to consistent access to students, with peer-led programmes proposed as a way forward.

This cluster randomised controlled trial targeted children aged 12–13 years, …
New phage type among methicillin-resistant Staphylococcus aureus associated with a local outbreak in Belgium during 2002
Authors: C. Wildemauwe, C. Godard, R. Joseph, R. De Ryck, A. Deplano, S. Damée, E. Van Bossuyt, R. Vanhoof, M. Struelens
Journal: Clinical Microbiology and Infection (2006)
Transduction of psychosocial stress into the neurobiology of recurrent affective disorder
Authors: R M Post
Journal: American Journal of Psychiatry (1992)

Early clinical observations and recent systematic studies overwhelmingly document a greater role for psychosocial stressors in association with the first episode of major affective disorder than with subsequent episodes. The author postulates that both sensitization to stressors and episode sensitization occur and become encoded at the level of gene expression. In particular, stressors and the biochemical concomitants of the episodes themselves can induce the protooncogene c-fos and related transcription factors, which then affect the expression of transmitters, receptors, and neuropeptides that alter responsivity in a long-lasting fashion. Thus, both stressors and episodes may leave residual traces and vulnerabilities to further occurrences of affective illness. These data and concepts suggest that the biochemical and anatomical substrates underlying the affective disorders evolve over time as a function of recurrences, as does pharmacological responsivity. This formulation highlights the critical importance of early intervention in the illness in order to prevent malignant transformation to rapid cycling, spontaneous episodes, and refractoriness to drug treatment.
Enabling dual cellular destinations of polymeric nanoparticles for treatment following partial injury to the central nervous system
Authors: I. Lozić, R.V. Hartz, C.A. Bartlett, J.A. Shaw, M. Archer, P.S.R. Naidu, N.M. Smith, S.A. Dunlop, K. Swaminathan Iyer, M.R. Kilburn, M. Fitzgerald
Journal: Biomaterials (2015)
Single-Agent Monoclonal Antibody Efficacy in Bulky Non-Hodgkin's Lymphoma: Results of a Phase II Trial of Rituximab
Authors: T. A. Davis, C. A. White, A. J. Grillo-López, W. S. Velásquez, B. Link, D. G. Maloney, R. O. Dillman, M. E. Williams, A. Mohrbacher, R. Weaver, S. Dowden, R. Levy
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A phase II trial was performed to evaluate the safety and efficacy of rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with bulky (&gt; 10-cm lesion) relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-one patients received intravenous infusions of rituximab 375 mg/m 2 weekly for four doses. All patients had at least one prior therapy (median, three; range, one to 13) and had progressive disease at study entry. Patients were a median of 4 years from diagnosis. RESULTS: No patient had treatment discontinued because of an adverse event. No patient developed human antichimeric antibody. The overall response rate in 28 assessable patients was 43% with a median time to progression of 8.1 months (range, 4.5 to 18.6+ months) and median duration of response of 5.9 months (range, 2.8 to 12.1+ months). The average decrease in lesion size in patients who achieved a partial response was 76%, and patients with stable disease had a decrease in average lesion size of 26%. Median serum antibody concentration was higher in responders compared with nonresponders, and a negative correlation was shown between antibody concentration and tumor bulk at baseline. CONCLUSION: Rituximab single-agent outpatient therapy is safe and shows significant clinical activity in patients with bulky relapsed or refractory low-grade or follicular B-cell NHL.
TLR7 gene deficiency and early-life pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice
Authors: Gerard Kaiko, Zhixuan Loh, Kirsten Spann, Jason Lynch, Amit Lalwani, Sophia Davidson, Paul Foster, Simon Phipps
Journal: European Respiratory Journal (2013)

Respiratory viruses are a major risk factor for both asthma inception and exacerbations, an association that may be related to a genetic defect in toll-like receptor (TLR)7-mediated signalling and impaired type I IFN responses, both reported in asthmatics. Wildtype (WT) and TLR7 gene-deleted mice were inoculated with rodent-specific pathogen pneumonia virus of mice (PVM) at 1 (primary), 7 (secondary) and 13 (tertiary) weeks of age and pathological features of bronchiolitis or asthma assessed. In some experiments, low dose cockraoch antigen was administered intransally at 3, 10, 17, and 31 days post primary infection. Here, we demonstrate that in absence of TLR7, PVM infection increased inflammasome activation, sloughing and viral load in the mucosal epithelium. This damage was associated with greater T helper 2 (Th2) immunity as evidenced by elevated nuocyte recruitment, and IL-33 and Th2 type cytokine expression. A secondary or tertairy infection of TLR7-deficient but not WT mice induced all of the cardinal pathophysiologic features of asthma, including Th2 cytokine and IgE production, eosinophilia, mast cell hyperplasia, increased airway smooth muscle and airways hyper-reactivity in a memory CD4+ T cell-dependent manner. PVM infection potentiated allergic sensitisation to cockroach antigen and exacerbated cockroach-induced allergic asthma. Moreover, this phenotype was significantly greater in TLR7-deficient mice. Our findings highlight how a clinically relevant gene-environment interaction may be causal in the development of asthma, and predispose toward an aberrant adaptive response that underlies virus-induced exacerbations in later life.
Heritable Variations in Growth Potential and Morphology Within a Clone of Balb/3T3 Cells and Their Relation to Tumor Formation&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: H Rubin, B M Chu, P Arnstein
Journal: JNCI Journal of the National Cancer Institute (1983)

A nontransformed clone and a spontaneously transformed clone were isolated from a twice-recloned line of Balb/3T3 cells. At different times two sublines were initiated from the nontransformed clone, and three were initiated from the transformed clone. The sublines were maintained in parallel passages under the same conditions. Each subline was distinctive in appearance and fell into the same rank order in a variety of growth parameters in vitro. Colony formation in agar and tumor formation in mice occurred only in the morphologically transformed sublines, but there was no quantitative correlation between the two properties or with the rate of glucose utilization. Two of the cell populations derived from noninbred NIH nude mouse tumors of the 3 transformed sublines differed in agar colony formation from the parental sublines. The results indicate that there is an immense capacity for variation in cultured animal cells involving many unrelated characteristics expressed in a way that is difficult, if not impossible, to explain by conventional genetic models.
Non-invasive haemodynamic measurement to detect treatment response in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia
Authors: Gregory Keir, Tamera Corte, Konstantinos Dimopoulos, Michael Gatzoulis, Philip Marino, Elisabetta Renzoni, Toby Maher, Athol Wells, Stephen J. Wort
Journal: European Respiratory Journal (2014)

BACKGROUND: In fibrotic idiopathic interstitial pneumonia (IIP), the presence of pulmonary hypertension (PH) confers significant additional morbidity and mortality. Non-invasive assessment of pulmonary blood flow (using inert gas rebreathing techniques with the Innocor device) has been validated against right heart catheter (RHC), and has proven a useful measure of treatment response in pre-capillary PH.  METHODS: In a randomized, double-blind, placebo-controlled study assessing the efficacy of bosentan in fibrotic IIP associated PH (the BPHIT study), non-invasive assessment of pulmonary blood flow (PBF INNOCOR ) was performed in a subgroup of patients at baseline and after 16 weeks of therapy, and compared with concurrent right heart catheter, echocardiographic and functional parameters.  RESULTS: Twenty-five of 60 patients (14 men; mean age 67.7±8.6 years) were recruited to the Innocor sub-study. Baseline assessment revealed significant fibrotic IIP (FVC 58.5±15.1%, DLco 23.5±8.2%) and PH (mPAP 33.6±6.5 mmHg, PVRi 11.3±4.6).  At baseline, there was a modest correlation between RHC CO  and PBF INNOCOR  (r=0.49; p=0.01). Assessing response to therapy after 16 weeks, we found a positive correlation between change in PBF INNOCOR  and change in 6MWD (r=0.54, p=0.04). There was no significant correlation between change in PBF INNOCOR  and change in RHC haemodynamics following therapy.  CONCLUSION: Change in non-invasive PBF measurement correlates more closely with functional change than with invasive haemodynamics in fibrotic IIP following treatment, and may offer a simple, readily performed measure complementing 6MWT.
Ascitic fluid TREM-1 for the diagnosis of spontaneous bacterial peritonitis
Authors: L Ichou, N Carbonell, P E Rautou, L Laurans, S Bourcier, C Pichereau, J L Baudel, J B Nousbaum, C Renou, R Anty, J Tankovic, E Maury, B Guidet, L Landraud, H Ait-Oufella
Journal: Gut (2015)

We read with interest the study by Knoop et al 1 who reported deleterious effects of antibiotics on the intestinal microflora. This observation should motivate the development of powerful tools for the diagnosis of infections to limit inappropriate antibiotic prescription. Spontaneous bacterial peritonitis (SBP) in patients with cirrhosis2 is a frequent life-threatening complication3 whose diagnosis is based on manual ascitic polymorphonuclear (PMN) count higher than 250 cells/μL.4 However, manual measurement of PMN count is operator dependent, makes quality control difficult and can delay the diagnosis.5 Recently, we have evaluated the validity and utility of ascitic fluid triggering receptors expressed on myeloid cells-1 (TREM-1) levels for the diagnosis of SBP. TREM-1 for triggering receptors expressed on myeloid cells-1 6 is a receptor expressed and released by innate inflammatory cells after exposure to bacteria membrane components.7 

From February to October 2014, we prospectively included in a test cohort all consecutive patients older than 18 years with cirrhosis admitted to two departments of hepatology and one intensive care …
Follow-up of acute pyelonephritis in children by Tc-99m DMSA scintigraphy: quantitative and qualitative assessment.
Authors: LENA WALLIN, INGEMAR HELIN, MARIKA BAJC
Journal: Clinical Nuclear Medicine (2001)

The author's goal was to create a system to identify children at risk for development of progressive renal damage.Thirty-four children were examined with Tc-99m DMSA scintigraphy in the acute stage of an initial episode of pyelonephritis, after 6 months, and again after 1 year. The scintigraphic findings were correlated with clinical and laboratory data.All children had parenchymal defects in the acute stage: 93% of the kidneys and 85% bilaterally. After 6 months, the defects had diminished or disappeared in 66% of the kidneys. New defects appeared in 22%. At 1 year, no further improvement was seen in the kidneys, with an improved or unchanged pattern at 6 months. New defects appeared in 34%. Mean kidney activity uptake expressed as the percentage of administered dose (KU/AD), was low in the acute stage, increased at 6 months, with no further significant increase at 1 year. Eighty-three percent of children with urine cultures growing > or = 104 bacteria/ml at follow-up had decreased KU/AD values, whereas all children with urine cultures growing < 104 bacteria/ml had increased KU/AD values.Quantitative assessment increases the sensitivity of Tc-99m DMSA scintigraphy. Follow-up with this method makes it possible to identify the children with decreasing renal tubular function who may be at risk for progressive renal damage. Moderate bacteruria of 104 bacteria/ml urine is associated with deterioration of renal tubular function.
Detection of occult lymphoma in the peripheral blood and bone marrow of patients with untreated early-stage and advanced-stage follicular lymphoma.
Authors: N L Berinstein, M D Reis, B Y Ngan, C A Sawka, H H Jamal, B Kuzniar
Journal: Journal of Clinical Oncology (1993)

The object of this study was to compare the relative sensitivities of morphologic, immunophenotypic, gene rearrangement, cytogenetic, and polymerase chain reaction (PCR) analyses in the detection of lymphoma cells in the bone marrow and peripheral blood of patients with follicular lymphoma.Bone marrow and peripheral-blood samples from 28 newly diagnosed patients with follicular lymphoma referred from several different medical centers were assessed. Routine morphologic assessment was performed initially and the remainder of the sample was aliquoted for DNA extraction to be used for gene rearrangement and PCR analyses and for immunophenotypic and cytogenetic analyses where a sufficient amount of sample remained.Morphologic assessment of the bone marrow was positive for lymphoma cells in 11 of 28 patients. PCR amplification of t(14;18) breakpoint DNA detected lymphoma cells in 17 of 24 patients assessed. Morphologic assessment detected lymphoma cells in three bone marrow samples that were negative by PCR. PCR analysis was the only method able to detect circulating lymphoma cells in peripheral blood at diagnosis and was positive in 15 of 24 samples. The other methods of assessment did not show lymphoma in any samples in which lymphoma was not detected by morphologic or PCR analysis. Lymphoma cells were found in the bone marrow and/or peripheral blood as frequently in early-stage patients as in advanced-stage patients.PCR amplification of t(14;18) breakpoint DNA together with morphologic assessment had the highest yield of detecting lymphoma cells in the bone marrow and/or peripheral blood of our population of newly diagnosed patients with follicular lymphoma. The clinical significance and prognostic importance of lymphoma cells detected by PCR in the bone marrow and/or peripheral blood of newly diagnosed follicular lymphoma patients awaits long-term follow-up data of these and additional patients.
Non-invasive ventilation in neuromuscular diseases. A 15-year retrospective study
Authors: Adeline Metchedjin, Claudio Rabec, Marjolaine Georges, Ntumba Kabeya, Ameline Vagner, Philippe Camus
Journal: European Respiratory Journal (2013)

Non-invasive ventilation (NIV) has been shown to reduce respiratory morbi-mortality in neuromuscular disorders (NMD). We conducted a retrospective study including NMD patients in whom long term NIV was instituted in our centre over the last 15 years.   Methods:  All NMD patients (p) in whom NIV was started between 1997 and 2011 were included. They were classified in 3 groups regarding the pattern of NMD: rapidly progressive ( RP) , early-onset myopathies ( EOM ) and late-onset myopathies ( LOM ). Clinical, epidemiological and lung function data at the time of NIV were collected. Criteria leading to introduce NIV and prognosis were analyzed.   Results:  Eighty seven patients (63% male, age 58±16 y) were included in the study; 55 (63%) had RP (age 65±11 y), 24 (28%) LOM (age 55±12 y) and 8 (9%) EOM (age 21±4 y). Time (in years) between diagnosis and NIV was 3.2±4 (RP), 26±13 (LOM) and 18±6 (EOM). In 17 (19.5%), NIV was begun during an acute episode (13 RP, 3 LOM, 1 EOM). In the remaining cases, NIV decision was based on at least one of the following criteria: hypercapnia (38 p, 44%), symptoms (35 p, 40%), lung test abnormalities (27 p, 32%), nocturnal SpO2 (28 p, 32%) or tcPCO2 (16 p, 18%) abnormalities. In sixty patients (69%) NIV decision was based on more than one abnormality. In eighty six patient (99%) NIV was initiated by using a pressure mode. Length of time on NIV (months) before death or tracheostomy was 17±15 (RP), 78±47 (LOM) and 84±45 (EOM).   Conclusion:  NIV is still initiated during an acute episode in 19.5% of our patients. In the remaining cases, symptoms and diurnal hypercapnia were the main factors leading to NIV institution; but in most cases NIV decision was based on more than one abnormality.
Chief medical officer's guidelines are right
Authors: A L Wood, S J O'Brien, A M Geddes
Journal: BMJ (1994)

damage in both clinical studies and animal models of meningitis.Diagnosing meningococcal meningitis in the community may be extremely difficult.General practitioners should not give dexamethasone in the home as many patients would be treated inappropriately.There have been no placebo controlled trials of dexamethasone to support its use in meningococcal septic shock, but trials of steroids in adult patients with other forms of Gram negative sepsis have shown no benefit.3We stand by our recent recommendation that general practitioners should give parenteral anti- biotics before admission to all patients suspected of having meningococcal disease.4In all five health districts that participated in a study there was a trend towards increased survival when benzylpenicillin was given before admission, with greatest benefit in the patients who were most ill- those with a haemorrhagic rash.5We therefore endorse the chief medical officer's advice.During the winter general practitioners should ensure that they carry benzylpenicillin among their emergency drugs.If they see a patient in whom they suspect meningococcal disease, especially if a rash is present, they should give a dose, ideally intravenously, before urgently arranging admission to hospital.Admitting paediatricians can remind general practitioner colleagues over the telephone of the value of this treatment.Whether or not benzylpenicillin is given, immediate transfer to hospital is the next urgent priority.