tbuckley/cabot-search huggingface dataset:
Smoking and asthma: dangerous liaisons
Authors: Riccardo Polosa, Neil C. Thomson
Journal: European Respiratory Journal (2012)

Cigarette smoking and asthma interact to induce important adverse effects on clinical, prognostic and therapeutic outcomes. This review examines recent evidence on the harmful effects of smoking in asthma, possible underlying inflammatory mechanisms for this altered response, management options for these patients and potential future therapeutic directions. Active smokers, particularly females, are at risk of developing asthma. Prevalence rates for smoking in asthma are relatively close to those found in the general population. Smokers with asthma experience worse asthma control than nonsmokers with asthma. Mechanisms for the adverse effects of smoking in asthma include altered airway inflammation and corticosteroid insensitivity. Quitting smoking can improve symptoms and lung function, but the low rates of smoking cessation highlights the need for improved strategies for managing these patients. Clinical trials assessing new therapies for asthma need to enrol smokers to identify treatments that are effective in the asthma smoking phenotype.
Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis
Authors: Nagendra Singh, Ashish Gurav, Sathish Sivaprakasam, Evan Brady, Ravi Padia, Huidong Shi, Muthusamy Thangaraju, Puttur D. Prasad, Santhakumar Manicassamy, David H. Munn, Jeffrey R. Lee, Stefan Offermanns, Vadivel Ganapathy
Journal: Immunity (2014)
Imatinib mesylate for lymphocytic variant of hypereosinophilic syndrome
Authors: Grzegorz Helbig
Journal: American Journal of Hematology (2011)

With a great interest I read a paper by Christoforidou et al. [1] showing the high efficacy of imatinib mesylate (IM) in a patient with L-HES and undetectable FIP1L1-PDGFRA (F/P) fusion transcript. However, after reading this case description, it seems that several issues need to be clarified and commented. The diagnosis of L-HES requires the detection of the abnormal T-cell phenotype in peripheral blood by flow cytometry and the presence of T-cell receptor clonal rearrangement [2]. It was demonstrated that clonal TCR rearrangement was detectable in patients with F/P mutation and treatment with IM resulted in disappearance of the clonal TCR pattern [3]. In this publication, the authors described a patient with lymphocytosis involving clonal but phenotypically normal CD4+ cell population, but these cells were detected in marrow. I wonder if these cells were also found in peripheral blood? The presence of CD4+ cells in patients with hypereosinophilic syndromes has already been demonstrated by other study groups, but it should be highlighted that this finding is extremely rare. The occurrence of such a T-cell population is usually associated with other features of T-cell mediated hypereosinophilia, e.g., increased serum IgE levels or cytokine and chemokine overproduction [4, 5]. These results are needed to better characterize this variant but they are lacking in this report. Corticosteroids (CS) remain a treatment of choice for patients with L-HES [2]. The authors reported severe side effects after therapy with steroids so they were discontinued. It was demonstrated in most studies that CS resulted in decrease of blood eosinophilia and resolution of clinical symptoms but the proportion of abnormal T-cell remained unaffected [6, 7]. In relation to this observation, I would expect such data from the authors of this presentation. We should keep in mind that treatment with IM, especially at a dose of 400 mg daily is expensive and associated with numerous side effects. Therefore, it seems rational to initiate IM only for patients who developed severe steroid-related complications and still require the continuation of treatment. Based on the presented case, it is difficult to judge that IM led to remission in a patient with L-HES. The therapy resulted in decrease of blood eosinophilia and withdrawal of some clinical symptoms, but in fact IM did not affect eosinophilic infiltration of the colon. The proportion of a clonal T-cell population remained intact. This case has shown that IM may remain an interesting therapeutic option but only for those patients who are resistant or intolerant to CS. As the abnormal T-cell subset remained unchanged after IM, we may expect that IM and CS will not prevent those patients from lymphoma transformation. Grzegorz Helbig*, * Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
Ischaemic preconditioning: present position and future directions
Authors: D Yellon
Journal: Cardiovascular Research (1998)

Preconditioning the myocardium using short episodes of sublethal ischaemia will delay the onset of necrosis during a subsequent lethal ischaemic insult. This powerful protective adaptation of the myocyte has also been observed in other cell types. The potential for clinical application to benefit patients with a variety of pathological conditions has led to an expansion in our knowledge concerning the pathophysiology of ischemia-reperfusion injury and the regulatory mechanisms underlying cellular metabolism. We feel it is timely to assess the current position in this field and provide a critical appraisal to facilitate future research.
Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments.
Authors: Y Kurosawa, S Tonegawa
Journal: The Journal of Experimental Medicine (1982)

We have identified, cloned, and sequenced eight different DNA segments encoding the diversity (D) regions of mouse immunoglobulin heavy-chain genes. Like the two D segments previously characterized (16, 17), all eight D segments are flanked by characteristic heptamers and nonamers separated by 12-bp spacers. These 10 D segments, and several more D segments identified but not yet sequenced, can be classified into three families based on the extent of sequence homology. The SP2 family consists of nine highly homologous D segments that are all 17-bp long and clustered in a chromosomal region of approximately 60 kb. The FL16 family consists of up to four D segments, two of which were mapped in the 5' end region of the SP2-D cluster. The two FL16D segments are 23 and 17 bp long. The third, the Q52 family, is a single-member family of the 10-bp-long DQ52, located 700 bp 5' to the JH cluster. We argue that the D-region sequences of the majority of heavy chain genes arise from these germline D segments by various somatic mechanisms, including joining of multiple D segments. We present a specific model of D-D joining that does not violate the 12/23-bp spacer rule.
Carbamylation of Serum Albumin as a Risk Factor for Mortality in Patients with Kidney Failure
Authors: Anders H. Berg, Christiane Drechsler, Julia Wenger, Roberto Buccafusca, Tammy Hod, Sahir Kalim, Wenda Ramma, Samir M. Parikh, Hanno Steen, David J. Friedman, John Danziger, Christoph Wanner, Ravi Thadhani, S. Ananth Karumanchi
Journal: Science Translational Medicine (2013)

Increased carbamylation of serum albumin is associated with increased mortality in patients with kidney failure.
BI-04 * PRE-OPERATIVE LOW TRI-IODOTHYRONINE SYNDROME IS ASSOCIATED WITH GREATER 6-MONTH MORTALITY RATE OF NEUROSURGICAL BRAIN TUMOR PATIENTS
Authors: A. Bunevicius, S. Tamasauskas, V. P. Deltuva, A. Tamasauskas, R. Bunevicius
Journal: Neuro-Oncology (2014)

BACKGROUND: We have previously demonstrated that pre-operative low tri-iodothyronine (T3) syndrome is a significant predictor of poor discharge outcomes in patients admitted for scheduled brain tumor surgery. In the present study we investigated an association of pre-operative low T3 syndrome with 6-month survival rate in neurosurgical brain tumor patients. METHODS: Two-hundred and forty-nine consecutive patients (166 women; age 55.6 ± 15.2 years) admitted for scheduled brain tumor surgery at the Department of Neurosurgery of the Lithuanian University of Health Sciences agreed to participate in the study. On admission, blood samples were drawn for evaluation of thyroid hormone concentrations. Low T3 syndrome was defined as free T3 concentrations of 1.1 pg/ml or lower. Final histological diagnoses of brain tumor were evaluated according to the pathology reports. Survival data were obtained from the national death registry. RESULTS: Ninety-three (37%) patients were diagnosed with meningioma, 48 (19%) – glioblastoma, 36 (15%) – pituitary adenoma, 19 (8%) – low grade glioma, 14 (6%) acoustic nerve neurinoma, and 10 (4%) – metastatic brain tumor. There were 28 (12%) deaths within a 6-month period following brain tumor surgery. Six-month mortality rate was the greatest in metastatic brain tumor patients (n = 6; 60%), followed by glioblastoma (n = 12; 25%) and meningioma (n = 7; 7.5%) patients. Pre-operative low T3 syndrome was associated with greater 6-month mortality rate (HR = 3.46, 95%CI 1.51 to 7.87, p = 0.003) in a total sample of patients. In subgroup analyses we have found that pre-operative low T3 syndrome was associated with greater 6-month mortality rate in glioblastoma patients (HR = 3.57 95%CI 1.07 to 11.90), p = 0.039) and in meningioma patients (HR = 5.59 95%CI 1.25 to 25.0, p = 0.025). CONCLUSIONS: Our findings suggest that pre-operative low T3 syndrome is associated with greater 6-month mortality rate of neurosurgical brain tumor patients. Low T3 syndrome can be an important prognostic biomarker of patients with brain tumors.
A fish oil diet minimizes hepatic reperfusion injury in the low-flow, reflow liver perfusion model
Authors: Zhi Zhong, Ronald G. Thurman
Journal: Hepatology (1995)

In this study, the effects of fish oil treatment on hepatic reperfusion injury in a low-flow, reflow perfusion model were investigated. Rats were fed powdered diets containing either 5% corn or 5% encapsulated fish oil for 13 to 15 days. Average daily food intake in both control and fish oil groups was about 20 g per rat, and weight gain averaged 9 g/rat/d. Livers were perfused at flow rates around 1 muL/g/min for 75 minutes, which caused cells in pericentral regions to become anoxic because of insufficient delivery of oxygen. When normal flow rates (about 4 mL/g/min) were restored for 40 minutes, reperfusion injury occurred. Upon reflow, lactate dehydrogenase (LDH) release increased from basal levels around 1 to 50 IU/g/h in livers from control rats, whereas fish oil treatment minimized values to 16 IU/g/h Rates of bile production reached 23 muL/g/h during reperfusion in livers from controls and 38 muL/g/h in the fish oil-treated group. Oxygen uptake was about 110 mumol/g/h during the reperfusion period in livers from both groups. Malondialdehyde (MDA), an end product of lipid peroxidation, was released into the effluent perfusate at rates around 80 nmol/g/h during reperfusion in controls, and values were not affected by fish oil treatment, Portal pressure, an indicator of hepatic microcirculation, increased from basal levels of 3 to 10.5 cm H2O during reperfusion in controls, but was only elevated to 8.3 cm H2O in the fish oil-treated group. In addition, Trypan Blue distribution time, another indicator of hepatic microcirculation, was reduced significantly by 44% by fish oil treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Neonatal deaths hamper India's infant mortality targets
Authors: G. Mudur
Journal: BMJ (2003)

India will be unable to achieve any substantial further drop in its infant mortality without first intensifying efforts to protect babies during their first four weeks of life, neonatologists told a conference in New Delhi last week.

An estimated 1.2 million babies die in India each year during the first month after birth, making up two thirds of the nation's infant mortality of 67 per thousand live births, doctors said at a symposium on the health of newborn infants.

The government wants to reduce infant mortality …
Relationship Between Insulin Resistance and an Endogenous Nitric Oxide Synthase Inhibitor
Authors: Markus C. Stühlinger
Journal: JAMA (2002)

RECENT ADULT TREATment panel report, the National Cholesterol Education Program recognized the metabolic syndrome (syndrome X; insulin resistance syndrome) as a new target of riskreduction therapy. 1 The metabolic syndrome is a cluster of closely associated and interdependent abnormalities, including insulin resistance, compensatory hyperinsulinemia, hyperuricemia, dyslipidemia, and hypertension, 2 and predisposes individuals to type 2 diabetes, hypertension, and coronary heart disease (CHD). 3,4n patients at high risk of CHD, endothelial dysfunction is observed in morphologically intact vessels before the onset of clinically manifested vascular disease. 5Indeed, there are several lines of evidence that indicate that endothelial function is compromised in situations with reduced sensitivity to endogenous insulin.For example, the increase of blood flow in the legs in response to methacholine (a measure of endothe-lium-dependent vasorelaxation) is reduced in nondiabetic insulin-resistant individuals. 6In addition, nitric oxidedependent, flow-mediated dilatation of the brachial artery is impaired in hypertensive 7 and normotensive 8 subjects with insulin resistance.Moreover, the endothelium also has been shown to modu-
Identification of acute myocardial infarction patients suitable for early hospital discharge after aggressive interventional therapy. Results from the Thrombolysis and Angioplasty in Acute Myocardial Infarction Registry.
Authors: D B Mark, K Sigmon, E J Topol, D J Kereiakes, D B Pryor, R J Candela, R M Califf
Journal: Circulation (1991)

BACKGROUND Very early (day 4) hospital discharge has recently been proposed for selected patients with acute myocardial infarction (MI). The purpose of this study was to determine the most useful factors for identifying acute MI patients treated with aggressive interventional therapy who could be safely discharged on day 4. METHODS AND RESULTS We studied 708 patients enrolled in the Thrombolysis and Angioplasty in Acute Myocardial Infarction trials I-III. Patients dying in the first 3 days and those with early (days 1-3) emergency coronary artery bypass graft surgery (CABG), late elective CABG (greater than or equal to day 4), or urgent/emergency CABG resulting from a late elective coronary angioplasty were excluded. The remaining 580 patients were randomly divided into a training sample (group 1) that was used to build a logistic regression model for predicting the absence of a late major complication and a test sample (group 2) that was used to validate this model. For this study, patients were considered appropriate for day 4 hospital discharge if they did not experience any of the following for 30 days after MI: death, reinfarction, cardiogenic shock, pulmonary edema, sustained hypotension, sustained ventricular tachycardia, high-grade atrioventricular block, acute ventricular septal defect, and recurrent ischemia necessitating urgent CABG. In group 1, four variables were independent predictors of freedom from late major complications: absence of early sustained ventricular tachycardia or ventricular fibrillation, absence of early sustained hypotension or cardiogenic shock, fewer coronary arteries with significant (greater than or equal to 75%) stenosis, and a higher left ventricular ejection fraction. In group 2, 23% of patients had a logistic model prediction of a 3% or less chance of a late complication. These patients had no deaths or reinfarctions by day 30 and a 3% late major complication rate. CONCLUSIONS The results of early cardiac catheterization and the absence of selected early (days 1-3) major complications do allow identification of a low risk subgroup of acute MI patients that may be suitable for very early discharge.
Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases
Authors: Thomas A. Wynn
Journal: Journal of Clinical Investigation (2007)

Fibroproliferative diseases, including the pulmonary fibroses, systemic sclerosis, liver cirrhosis, cardiovascular disease, progressive kidney disease, and macular degeneration, are a leading cause of morbidity and mortality and can affect all tissues and organ systems. Fibrotic tissue remodeling can also influence cancer metastasis and accelerate chronic graft rejection in transplant recipients. Nevertheless, despite its enormous impact on human health, there are currently no approved treatments that directly target the mechanism(s) of fibrosis. The primary goals of this Review series on fibrotic diseases are to discuss some of the major fibroproliferative diseases and to identify the common and unique mechanisms of fibrogenesis that might be exploited in the development of effective antifibrotic therapies.
Genomic Sequencing in Newborn Screening Programs—Reply
Authors: Aaron J. Goldenberg, Richard R. Sharp
Journal: JAMA (2012)

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
Abstract 2325: The crystal structure of the ERK2/norathyriol complex
Authors: Margarita Malakhova, Igor Kurinov, Jixia Li, Srinivasa Reddy, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2011)

Abstract Norathyriol is an active metabolite of mangiferin, one of the mango polyphenolic compounds that have been demonstrated to have anti-proliferative and pro-apoptotic activities against human leukemia, as well as human lung, breast, colon and prostate cancer cells. Norathyriol has been reported to inhibit the PMA-induced respiratory burst and aggregation of rat neutrophils by suppressing protein kinase C activity. We show that norathyriol targets extracellular signal-regulated kinase 2 (ERK2), which is activated in response to growth factors and cytokines, and is a key kinase in the Ras/Raf/MAPK signaling pathway, which is deregulated in many cancers. We determined the crystal structure of ERK2 complexed with norathyriol at 1.6 Å resolution. Human recombinant ERK2 was expressed, purified from E.coli and successfully crystallized. The protein crystals were soaked with norathyriol solution prior to the data collection. The norathyriol molecule is clearly visible in the electron density map inside the ATP-binding site below the phosphate-binding loop. Norathyriol is anchored to the ERK2 hinge region that connects the kinase N- and C-lobes by several hydrogen bonds. The side chain carboxyl of the gatekeeper residue Gln105 hydrogen bonded with the 7-OH group of norathyriol. The backbone of Asp106 and Met108 form hydrogen bonds with 6-OH group of norathyriol. We mutated Gln105 to alanine to weaken the norathyriol interaction with ERK2, and showed that the recombinant Q105A mutant exhibited impaired in vitro binding affinity to norathyriol compared with wild type. The Ile31, Val39, and Ala52 residues from the N-lobe contribute to the hydrophobic interactions with the xanthone moiety of norathyriol. These results indicate that norathyriol directly binds to the ATP-binding site of ERK2. The Ras/Raf mutation in many cancers causes the hyperactivation of ERK2 and unregulated cell proliferation. Recent reports indicate that knockdown of ERK2 inhibits growth of tumor cells, suggesting that ERK2 inhibition is a potential approach for the treatment of cancer. Norathyriol thus might be a potential therapeutic and chemopreventive lead compound targeting ERK2 in cancer cells where activation of the ERK2 pathway mediates the anti-apoptotic response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2325. doi:10.1158/1538-7445.AM2011-2325
Case 3-1968
Authors: Edwin P. Maynard, Richard B. Cohen
Journal: New England Journal of Medicine (1968)

Presentation Of CaseA fifty-year-old man was admitted to the hospital because of vomiting followed by coma.He had been well until one year previously, when there was the onset of intermittent crampy epigastric pain after meals and watery diarrhea with the passage of up to 15 stools daily. A gastrointestinal series was said to show a duodenal ulcer; the symptoms subsided with a bland diet and antacids. A follow-up gastrointestinal series was reported to show healing of the ulcer. Five months before entry severe, crampy epigastric pain recurred; the pain lasted for three to four minutes and subsided without . . .
SWOG S0722: Phase II Study of mTOR Inhibitor Everolimus (RAD001) in Advanced Malignant Pleural Mesothelioma (MPM)
Authors: Sai-Hong Ignatius Ou, James Moon, Linda L. Garland, Philip C. Mack, Joseph R. Testa, Anne S. Tsao, Antoniette J. Wozniak, David R. Gandara
Journal: Journal of Thoracic Oncology (2015)
The effect of indomethacin and other anti-inflammatory drugs on the renin-angiotensin system.
Authors: J C Romero, C L Dunlap, C G Strong
Journal: Journal of Clinical Investigation (1976)

The administration of two different doses of indomethacin, 9 and 18 mg/kg, to two different groups of rabbits was followed 6 h later by a significant decrease in plasma renin activity, and these levels were not increased by hemorrhage. The administration of 2 mg/kg of indomethacin did not alter the basal levels of plasma renin activity, but it was effective in diminishing the peripheral increase of renin produced by hemorrhage. Similar effects were obtained in other groups of rabbits treated with 9 mg/kg of meclofenamate or 18 mg or aspirin. The lowering effect of indomethacin on plasma renin activity is not specifically related to hemorrhage because it also prevented the increase in plasma renin activity elicited by 5 mg/kg of furosemide. Further studies showed that indomethacin did not exert any significant effect in vivo on the plasma level of renin substrate or on the generation of angiotensin from normal plasma by exogenous renin. And indomethacin did not interfere with the binding capacity of anti-angiotensin I for angiotensin I in the radioimmunoassay reaction or with the in vitro formation of angiotensin from hog renin-nephrectomized rabbit plasma reaction. The results thus indicate that the lowering effect of indomethacin on plasma renin activity is due to the interference with renal renin release. That this effect may be related to the blockade of prostaglandin synthesis is suggested by the similar effect exhibited by other blockers of prostaglandin synthesis.