tbuckley/cabot-search huggingface dataset:
Thymic stromal lymphopoietin activation of basophils in patients with allergic asthma is IL-3 dependent
Authors: Brittany M. Salter, John Paul Oliveria, Graeme Nusca, Steve G. Smith, Rick M. Watson, Micheal Comeau, Roma Sehmi, Gail M. Gauvreau
Journal: Journal of Allergy and Clinical Immunology (2015)
Weighing Reproductive Threats"Talking" Genetics GlossaryHepatitis C Drugs for VeteransSobering News About BoozeWeighing Reproductive Threats"Talking" Genetics GlossaryHepatitis C Drugs for VeteransSobering News About Booze
Authors: Joan Stephenson
Journal: JAMA (1999)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Preventing Type 1 Diabetes May Someday Become Possible
Authors: Brian Vastag
Journal: JAMA (2002)

WASHINGTON—Even as researchers continue to search for the roots of type 1 diabetes, a new drug to prevent the autoimmune disease awaits largescale human testing. If successful, it would brighten the clinical landscape considerably, possibly curtailing endless iterations of glucose testing and insulin injecting and the serious complications of the disease. DiaPep 277, a laboratory-made peptide, already appears to have helped a few patients. In a double-blind phase 2 trial, the drug maintained C-peptide levels—and by extension, pancreatic -cell function—in 15 human volunteers for up to 10 months (Lancet. 2001;358:1749-1753). It also prevented -cell destruction in newly diabetic mice (Diabetes. 1997;46:758-764). “The molecule blocked the disease even in animals at the brink of diabetes,” said Dana Elias, PhD, a researcher at Peptor Ltd, the Rehovot, Israel, company developing the drug. Lured by this performance, a committee appointed by the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK) is poised to fund wide-scale testing. “There are several [other drugs] under consideration, but DiaPep certainly looks good,” said Desmond Schatz, MD, a researcher at the University of Florida School of Medicine who sits on the steering committee for TrialNet, the NIDDK’s consortium of clinical testing centers. With the caveat that just a handful of subjects have been evaluated to date, steering committee director Jay Skyler, MD, said his committee is leaning toward approving trials. Safety is an important factor. “They’ve exposed over 200 people and essentially have no safety issues,” said Skyler, director of diabetes research at the University of Miami School of Medicine. This profile should ease acceptance of studies for the target groups; namely, children and adults with no overt diabetes but with at least a 50% chance of developing it within 5 years. The dream of preventing diabetes spurred an earlier NIDDK-sponsored trial of injected insulin in high-risk patients. The Diabetes Prevention Trial continues to provide a wealth of data regarding genetic and immunologic risk factors. However, the study unmasked injected insulin as unfit for prevention. According to an NIDDK fact sheet, and as presented at the 2001 American Diabetes Association annual meeting in Philadelphia, lowdose insulin failed to stave off type 1 diabetes in high-risk groups. Full results of that study have not yet been published; a concurrent trial testing oral insulin for prevention is still under way.
History and economics lessons in asymmetrical flu threats
Authors: N. Awofeso
Journal: BMJ (2009)

The process of combining predictive tools in epidemiology and biostatistics with those from history and economics to develop a sustainable framework for addressing the ongoing swine flu pandemic is a global multidisciplinary challenge. During the 1976 swine flu outbreak, a precipitate decision to produce and initiate mass vaccination led to more vaccine-related morbidity and mortality …
ISOLATED DISEASE OF THE PULMONARY VALVE AND ARTERY
Authors: A L HYMAN, L LEVY, R BAGNETTO, N K ORDWAY, E HULL
Journal: Annals of Internal Medicine (1951)

Excerpt The purpose of the present communication is to present seven cases of organic heart disease in which there is isolated involvement of the pulmonary artery or valve, and to indicate the importance of certain physical signs and laboratory procedures in their diagnosis. Each individual was studied while a patient in Charity Hospital at New Orleans. All but one were encountered within a few months of each other. Three patients are presented as examples of congenital isolated stenosis of the pulmonary valve, two as examples of acquired pulmonary valvulitis, and two as examples of pulmonary artery aneurysm secondary to infection. CONGENITAL
Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma
Authors: R.M. Anforth, T.C.M.P. Blumetti, R.F. Kefford, R. Sharma, R.A. Scolyer, S. Kossard, G.V. Long, P. Fernandez-Peñas
Journal: British Journal of Dermatology (2012)

Background Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma carrying relevant oncogenic mutations. Cutaneous reactions are frequent and significant. We conducted a systematic prospective dermatological review of all patients enrolled at a single institution in the phase I/II clinical trial of the mutant BRAF inhibitor dabrafenib (GSK2118436). Objectives To identify the cutaneous manifestations of the BRAF inhibitor dabrafenib; to form diagnostic criteria to standardize the diagnosis of verrucal keratotic squamoproliferative lesions; and to bring awareness to the medical community of the importance of dermatological assessment of patients taking dabrafenib. Methods Patients enrolled in the phase I/II trial (n = 43) were monitored for the development of new skin lesions. Each new lesion was photographed, a clinical diagnosis recorded and, where appropriate, a biopsy taken. Human papillomavirus (HPV) and p16 immunohistochemistry analyses were performed. Results The most frequently observed lesions were verrucal keratotic squamoproliferative lesions (49%), Grover's disease (27%) and reactive hyperkeratotic lesions on the soles, at points of friction (22%). Eighteen squamous cell carcinomas (SCCs) occurred in 20% of patients. Most SCCs appeared between weeks 6 and 24 following commencement of therapy on both sun-damaged and nonsun-damaged skin. All SCCs were well differentiated, five were of the keratoacanthoma type, and two were SCC in situ. Other lesions observed included seborrhoeic keratoses, epidermal cysts, acneiform eruptions, hair loss and changes in hair structure. HPV was negative in 15 of the 16 tissues studied and p16 expression was higher in SCCs compared with verrucal keratoses. Conclusions Administration of the mutant BRAF inhibitor dabrafenib is associated with induction of keratinocytic proliferation, which in some cases develops features of low-grade malignancy. Highly oncogenic HPV infection is unlikely to be a contributor to the formation of SCCs or verrucal keratoses.
Ocular albinism: evidence for a defect in an intracellular signal transduction system
Authors: M. Vittoria Schiaffino, Marilena d'Addio, Anna Alloni, Cinzia Baschirotto, Caterina Valetti, Katia Cortese, Claudia Puri, M. Teresa Bassi, Cristina Colla, Michele De Luca, Carlo Tacchetti, Andrea Ballabio
Journal: Nature Genetics (1999)
Abstract P148: Neck Circumference as an Independent Contributor to Cardio Metabolic Risk Factors - ELSA BRASIL
Authors: Cristina P Baena, Paulo A Lotufo, Maria J Fonseca, Isabela J Benseñor
Journal: Circulation (2015)

Background: Neck circumference is a proxy for upper body fat and it is a simple anthropometric measure. Therefore it could be a useful tool to identify individuals with cardiometabolic risk factors in the context of primary care. Hypothesis: Neck circumference is independently associated to cardiometabolic risk factors in an apparently healthy population. Methods: This is a cross-sectional analysis of baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort of 15105 civil servants aged 35-74 years. We excluded from this analysis those who fulfilled American Diabetes Association criteria for diabetes diagnosis, were taking antihypertensive and/or lipid-lowering drugs. A sex-specific analysis was conducted. Partial correlation (age-adjusted) was used. Risk factors were set as low HDL&lt;50mg/dL for women and &lt;40mg/dL for men, hypertriglyceridemia ≥ 150 mg/dl , hypertension as systolic blood pressure ≥130 mg/dl or diastolic blood pressure ≥85 mm Hg and insulin resistance(HOMA-IR ≥ 75th percentile). Logistic regression models were built to analyze the association between individual and clustered risk factors as dependent variables and 1-SD increase in neck circumference as independent variable. Multiple adjustments were subsequently performed for age, smoking, alcohol, body-mass index, waist and physical activity. Receiver Operating Curves were employed to find the best NC cut-off points for clustered risk factors. Results: We analyzed 3810 men (mean age= 49.0 ±8.3 yrs) and 4916 women (49.2 ±8.0 yrs). Mean NC was 38.9 (±2.6)cm for men and 33.4(±2.6)cm for women. NC positively correlated with systolic and diastolic blood pressure (r=0.21 and r=0.27), HOMA - IR (r=0.44), triglycerides (r=0.31) and negatively correlated with HDL (r= -0.21) in men (p&lt;0.001 for all) with similar results in women. Fully adjusted Odds Ratio (OR) (95% CI) of risk factor per SD increase in neck circumference in men and women were 1.29(1.14;1.46) and 1.42(1.28;1.57) for insulin resistance; 1.24(1.11;1.39) and 1.25(1.11;1.40) for hypertension; 1.33(1.19;1.49) and 1.42(1.29;1.63) for hypertriglyceridemia; 1.07(0.92;1.23) and 1.32 (1.19;1.43) for low HDL. Fully adjusted OR (95% CI) of 2 clustered risk factor per SD increase in neck circumference in men and women were 1.29(1.14;1.48) and 1.37(1.21;1.54 ). Fully adjusted OR (95% CI) of 3 or more clustered risk factors per SD increase in neck circumference in men and women were 1.33 (1.02;1.74) and 1.62 (1.33;1.92). Values of neck circumference of &gt;40 cm for men and &gt;34.1 cm for women were the best cut-off points for 3 or more clustered risk factors. Conclusion: Neck circumference is significantly and independently associated to cardiometabolic risk factors in a well-defined non-treated population. It should be considered as a marker of cardio metabolic risk factors in primary care settings.
Markers of cell proliferation contributes to the therapeutic effect of growth factor-LGF on experimental emphysema
Authors: Sandra Perez-Rial, Alvaro Giron-Martinez, Raul Terron-Exposito, Juan Jose Diaz-Gil, Nicolas Gonzalez-Mangado, German Peces-Barba
Journal: European Respiratory Journal (2014)

Emphysema is a major component of Chronic Obstructive Pulmonary Disease (COPD), considering cigarette smoke (CS) as the main risk factor. Currently, treatment of COPD is based on the administration of bronchodilators and corticosteroids to control symptoms and exacerbations, but there is no effective therapies directed to reverse the progression of the disease. Liver growth factor (LGF) is an albumin-bilirubin complex with mitogenic properties, whose therapeutic effects has been previously reported in several rodent models such as injured liver, Parkinson9s disease, testis degeneration, atherosclerosis, heart or hypertension.  To address the therapeutic effect of LGF, morphometric and lung function parameters, matrix metalloproteinase (MMP) activity and the expression of several markers such as VEGF, PCNA, 3NT and Nrf2 were assessed in air-exposed and CS-exposed C57BL/6j male mice with and without intraperitoneal injection of LGF administered after long-term cigarette smoke exposure (CSE).  CS-exposed mice presented a significant enlargement of alveolar spaces (Lm), higher alveolar internal area (AIA) and loss of lung function that correlated with higher MMP activity, higher expression of 3NT and lower expression of VEGF. CS-exposed mice and then injected with LGF, showed an amelioration of emphysema and improved lung function that correlated with lower MMP activity and 3NT expression, and higher levels of VEGF, PCNA and Nrf2.  This study provides evidence that LGF administration produced therapeutic effects once the lung damage was established, postulated as a promising strategy to revert the progression of COPD.
Abstract 1285: Wnt2 Plays a Key Role in Cardiac Development via a Non-canonical Pathway
Authors: Takeshi Onizuka, Shinsuke Yuasa, Kenichiro Shimoji, Motoaki Sano, Kensuke Kimura, Shinji Makino, Daihiko Hakuno, Mitsushige Murata, Hideaki Kanazawa, Hirotaka Yada, Takashi Kawakami, Toshimi Kageyama, Takaharu Katayama, Jin Endo, Hao Chen, Fumiyuki Hattori, Keiichi Fukuda, Satoshi Ogawa
Journal: Circulation (2007)

Embryonic stem (ES) cells are a promising source of cardiomyocytes, but their clinical application has been hindered by the lack of selective differentiation methods. Although several signals are i...
p53-induced apoptosis of prostate cancer cells requires XIAP down-regulation
Authors: Subhra Mohapatra, Baoky Chu, Xiuhua Zhao, W. Jack Pledger
Journal: Cancer Research (2005)

2263   This study was undertaken to investigate the role of purine analogues in modulating prostate cancer growth and to evaluate the potential X-linked inhibitors of apoptosis (XIAP) as a target for prostate cancer therapy. Purine analogues such as roscovitine and CGP74514A were tested in human prostate cancer models with various p53 status, LnCaP (p53 wt/wt), DU145 (p53mt/mt), and PC3 (p53null). Our results suggest that exposure to roscovitine and CGP74514A induced cell cycle arrest, mitochondria-dependent activation of caspase-9 and caspase-3 and apoptosis of both LnCaP and androgen refractory LnCaP (LnCaP-Rf) cells. The apoptosis in these cells was accompanied by stabilization of p53 and down-regulation of XIAP, but did not require inhibiton of Akt activity. Roscovitine and CGP74514A also induced down-regulation of XIAP in DU145 and PC3 cells, but moderate apoptosis was induced only when the cells were exposed to high dosage of drug, suggesting the requirement for functional p53. Accordingly, over-expression of p53 but not down-regulation of XIAP increased sensitivity of PC3 cells toward roscovitine and CGP74514A. Further, concomitant over-expression of wt p53 and down-regulation of XIAP induced apoptosis of LnCaP, DU145 and PC3 cells even in the absence of roscovitine. Together, these results suggest that lack of functional p53 and increased expression of XIAP contribute toward apoptosis-resistance in androgen-independent prostate cancer cells and should be targeted for inducing apoptosis in these cells.
The role of iCa, pH and albumin upon coagulation activities in benign and malignant effusions.
Authors: Frank Gieseler, Tobias Erhart, Momme Denker, Michael Clark, Christian Gespach, Peter Dohrmann, Christoph Mundhenke, Thomas Kunze
Journal: Cancer Research (2007)

3503  In the course of progressive metastatic cancer, the development of malignant effusions, either as pleural, abdominal or pericardial manifestation, are severe complications and significant causes of death. In addition to the physical impairment due to large effusion volumes up to several liters, the treatment of these malignant effusions is complicated by the acquired high chemoresistance of the resident metastatic cancer cells to anticancer drugs. We have previously shown that activated coagulation factors are potential molecular inducers of chemo-resistance (Nguyen et al. Oncogene 2005, 242; Schiller et al Int J Clin Pharmacol Ther 2002, 40).  The activation of the tissue factor-pathway of coagulation-activation involving coagulation FX, FIX, FVII, FII which have a number of common characteristics: They are synthesized in the liver using a vitamin K-dependent pathway, are small enough (  A series of 55 effusions from patients suffering from cancer from following locations has been included in the study: Mammary, 16; lung, 11; gastrointestinal 15; ovaries 4; misc (melanoma, Mesothelioma, sarcoma, etc.), 9. A spontaneous formation of pure fibrin was observed in most effusions (WEIGERT stain). This supports our hypothesis that thrombin activation, and subsequent fibrin formation, is generated by the activation of factors FX, FIX, FVII and FII. A strong correlation exists between iCa levels and fibrin formation. Ca 50% of the total calcium (tCa) was ionized (iCa/tCa = 0.59 Â± 0.12). The tCa concentrations in the effusions were 1.79 Â± 0.54 mmol/L. The relation of iCa / tCa linearly correlates with albumin concentrations in the effusions (R2=0.5), due to the high albumin binding-affinity of Ca. Albumin concentrations in the malignant effusions vary considerably (2.0 - 50.0 g/L). The pH values ranged be-tween 7.4 and 8.3 (mean 7.75 Â± 0.25).  In conclusion, the iCa levels within the effusions are a decisive factor for the activation of the tissue factor-pathway of coagulation-activation involving FX, FIX, FVII, FII. This activation, leading to local thrombin generation has been previously shown to be a survival factor for tumor cells involving G-protein coupled PAR-1 activation (Nguyen et al. Oncogene 2005, 242).
Fibrinogen, health status and hospitalization in patients with moderate to severe COPD
Authors: Vladimir Hodgev, Blagoi Marinov, Roman Kalinov, Lyudmila Vladimirova-Kitova, Fedya Nikolov, Stefan Kostianev
Journal: European Respiratory Journal (2011)

Background: There is evidence that COPD is a systemic illness. Serum biomarkers have been associated with clinically relevant variables.  Aim: To investigate the relationships between the blood level of fibrinogen and large group of clinical and functional parameters.  Patients and methods: Twenty-nine stable COPD patients (age [yr] = 63.4±8.6, FEV1% = 37±11%, BODE index = 3.7±1.8) were enrolled in the study. Pulmonary function tests, blood-gas measurements; echocardiography, brain natriuretic peptide (BNP); 6-minute walking test (6MWT) and cardiopulmonary exercise test (CPET) on a treadmill were performed. In addition, health status was evaluated by SGRQ (St George9s Respiratory Questionnaire) and CAT (COPD assessment test). The number of hospitalization, the need of antibiotic treatment and oral/intravenous corticosteroids (OICS) in the 12 months prior to evaluation were recorded.  Results: The mean value of fibrinogen was 3.0±0.8 [g/L]. Fibrinogen correlated significantly with health status - SGRQ (r =-0.49, p = 0.008), CAT (r =-0.44, p = 0.016) and hospitalizations (r = -0.50, p = 0.006), and OICS application (r = - 0.48, p = 0.012). Differentiation of patients by value of fibrinogen (> 3 g/L ≤) discriminated them with respect to last year hospitalisations (1.8±1.9 vs 0.6±1.3; p   Conclusion: Blood level of fibrinogen was related to health status and hospitalization in patients with moderate to severe COPD.
Abstract 4550: Differential PARP inhibitors' effects on cell cycle and consequently homologous DNA damage repair
Authors: Petar Jelinic, Douglas A. Levine
Journal: Cancer Research (2014)

Abstract Background: Poly (ADP)-ribose polymerase (PARP) inhibition has been explored in pre-clinical and clinical studies with greatest successes demonstrated in homologous DNA damage repair (HDR) pathway-deficient cancer patients. PARP inhibitor's (PARPis) potency to inhibit PARP's catalytic activity is well established; however non-catalytic effects that may add to their therapeutic properties are not fully understood. Our objective was to comparatively evaluate non-catalytic effects of olaparib and veliparib, the two most widely used PARPis in clinical trials, with a particular focus on cell cycle effects and HDR. Methods: To measure DNA damage repair activity upon PARPi treatment, we used a well-established DR-GFP reporter assay in two model cell lines, U2OSDR-GFP and H1299DR-GFP. Cell cycle progression was assessed by propidium iodide and monitored by flow cytometry. Depletion of targeted mRNAs was performed by standard siRNA knock-down technique using electroporation for transfection. Immunoblotting was used to confirm cell cycle results and demonstrate replicative stress on the protein expression levels. Results: We found a dramatic decrease in DNA damage repair activity in olaparib- versus veliparib-treated U2OSDR-GFP p53 wild type cells, regardless of inhibitory potency. This decrease in HDR activity was a result of olaparib triggering a cell cycle arrest-like effect as a response to strong replicative stress. Lack of the same effect in p53-null cells suggests that olaparib's effect is p53-dependent, which was confirmed in U2OSDR-GFP cells depleted of p53. Finally, CHK1 is strongly phosphorylated in cells treated with olaparib but not veliparib, confirming cells differential response to these two PARPis. Conclusion: These data demonstrate that olaparib and veliparib differ in their non-catalytic inhibitory effects, with olaparib but not veliparib mitigating DNA damage repair activity via cell cycle arrest-like effects in a p53-WT background. Moreover, olaparib but not veliparib triggers CHK1 phosphorylation, which suggests differential levels of replicative stress. This new insight into olaparib's and veliparib's mechanism of action should be considered when developing inclusion criteria for treatment of cancer patients with these PARP inhibitors. Citation Format: Petar Jelinic, Douglas A. Levine. Differential PARP inhibitors' effects on cell cycle and consequently homologous DNA damage repair. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4550. doi:10.1158/1538-7445.AM2014-4550
To Err Is Human
Authors: Lucian L. Leape, Donald M. Berwick
Journal: JAMA (2005)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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