tbuckley/cabot-search huggingface dataset:
Pim Kinases as Therapeutic Targets in Early Rheumatoid Arthritis
Authors: Nicola J. Maney, Henrique Lemos, Ben Barron‐Millar, Christopher Carey, Ian Herron, Amy E. Anderson, Andrew L. Mellor, John D. Isaacs, Arthur G. Pratt
Journal: Arthritis & Rheumatology (2021)

Objective As well as being an established oncoprotein and therapeutic target in cancer, proviral integration site for Moloney murine leukemia virus 1 (Pim‐1) is implicated in human autoimmunity. This study was undertaken to investigate Pim‐1 and its family members as potential therapeutic targets in early rheumatoid arthritis (RA). Methods A flow cytometry assay for PIM1 transcript measurement in peripheral blood mononuclear cells from patients with early arthritis was validated and applied as a biomarker of Pim‐1 activity at the cellular level. Synovial protein expression was similarly determined by multiplex immunofluorescence in tissue samples from untreated RA patients and non‐RA disease controls. Functional consequences of Pim kinase family manipulation in freshly isolated CD4+ T cells from these individuals were ascertained, along with the impact of Pim inhibition on mice with collagen‐induced arthritis (CIA). Results The percentage of circulating CD4+ T cells positive for PIM1 transcript by flow cytometry proved a faithful surrogate for gene expression and was significantly higher in patients with early RA than in those with other diseases. Pim‐1 protein levels were similarly up‐regulated in synovial CD4+ T cells from patients with early RA. Ex vivo, exposure of T cell receptor–stimulated early RA CD4+ T cells to Pim kinase inhibitors restrained their activation and proliferative capacity. Diminished production of proinflammatory cytokines (interferon‐γ and interleukin‐17) and an expanded CD25 high FoxP3+ Treg cell fraction were also observed in exposed versus unexposed cells. Finally, administration of Pim inhibitors robustly limited arthritis progression and cartilage destruction in CIA. Conclusion Our findings indicate that Pim kinases are plausible therapeutic targets in a readily identifiable subgroup of patients with early RA. Repurposing of Pim inhibitors for this disease should be considered.
Action of intracoronary nitroglycerin in refractory coronary artery spasm.
Authors: C JPepine, R LFeldman, C RConti
Journal: Circulation (1982)

Coronary artery spasm usually responds to sublingual nitroglycerin. This report describes four patients with variant angina and one patient with rest angina who had coronary spasm that was refractory to sublingual or i.v. nitroglycerin. In four patients, spasm occurred spontaneous and in one patient after 0.05 mg of ergonovine. In each case, 25-100 micrograms of intracoronary nitroglycerin promptly (30-45 seconds) resulted in reopacification of the vessel involved in spasm and resolution of evidence for ischemia. Thus, intracoronary nitroglycerin can reverse coronary artery spasm that does not respond to systemic nitroglycerin administration.
Choline uptake into renal phospholipids following renal ischemia in rats.
Authors: M BSiegel, L MLowenstein, N GLevinsky
Journal: Circulation Research (1979)

Renal phospholipid metabolism was studied after ischemia was induced by occlusion of the left renal artery in the rat. There was no change in the rate of cellular [14C]choline uptake after 25 or 60 minutes of ischemia. However, [14C]choline incorporation into phospholipid was two to three times greater in slices from the ischemic kidney than in slices from the contralateral control kidney. The increase occurred after 25 minutes of ischemia plus 15 minutes of reflow, and after 60 minutes of ischemia with or without reflow. When [14C]choline was injected into rats after a 60-minute period of renal ischemia, the rate of incorporation into phospholipid in the ischemic kidney was almost twice that of the control kidney. These results were similar to those of the in vitro experiments. Since virtually all of the cellular phospholipids of the kidney are present in cellular membranes, renal ischemia affects membrane metabolism. The mean distribution ratio of alpha-aminoisobutyric acid in slices of kidneys ischemic...
Intraventricular early diastolic filling during acute myocardial ischemia, assessment by multigated color m-mode Doppler echocardiography.
Authors: MStugaard, O ASmiseth, CRisöe, HIhlen
Journal: Circulation (1993)

BACKGROUNDColor M-mode Doppler echocardiography has been suggested as a new noninvasive technique for assessing left ventricular diastolic function. The present study investigated intraventricular filling pattern by color M-mode Doppler in patients during percutaneous transluminal coronary angioplasty (PTCA). In a dog model of myocardial ischemia, the color M-mode flow pattern was related to indices of global and regional myocardial function.METHODS AND RESULTSFrom color M-mode images, the time difference (TD) between occurrence of peak velocity in the apical region and at the mitral tip was determined in 20 patients and eight anesthetized dogs during coronary occlusions. During PTCA, the timing of peak velocity was progressively delayed from mitral valve to apex. Consistent with this, the dog model showed delayed apical filling during coronary occlusion; TD increased from 18 +/- 4 to 71 +/- 9 milliseconds (P < .01). In the ischemic region, systolic shortening (sonomicrometry) decreased from 20 +/- 3% to ...
Pulmonary atresia with ventricular septal defect in adults.
Authors: A JMarelli, J KPerloff, J SChild, HLaks
Journal: Circulation (1994)

BACKGROUNDMultistage surgery culminating in completed hemodynamic repair is now performed for pulmonary atresia with ventricular septal defect (PA-VSD). Justification for operation in patients with an adequate collateral pulmonary circulation is controversial. Data on natural adult survival are scant but are necessary to provide the rationale for multistage reconstructive procedures.METHODS AND RESULTSAll cyanotic adults with PA-VSD in the UCLA Adult Congenital Heart Disease Center Registry from 1978 through 1992 formed the basis for this study. Registry data and echocardiographic, hemodynamic, and angiographic information were used to determine longevity, clinical course, and operative feasibility. Of 26 patients, 16 were unoperated when referred (group A), and 10 had been palliated before age 18 years (group B). Two thirds were 18 to 29 years old. Only 2 patients survived beyond age 40 years. Six died during follow-up at a mean age of 31 years (+/- 12.1 SD). Eight group A patients were in New York Heart...
Screening for Synchronous Esophageal Second Primary Tumors in Patients With Head and Neck Cancer
Authors: SEM van de Ven, W de Graaf, O Bugter, MCW Spaander, S Nikkessen, PJF de Jonge, JA Hardillo, A Sewnaik, DA Monserez, H Mast, S Keereweer, MJ Bruno, RJ Baatenburg de Jong, AD Koch
Journal: Endoscopy (2021)

Aims Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (SPTs). We aimed to determine the incidence, stage and outcome of synchronous esophageal SPTs in patients with HNSCC in a Western population.
Learning Curve Of Optical Diagnosis With A Resect And Discard Strategy For Screening Colonoscopy: Preliminary Results From The Discard3 Study
Authors: A Ahmad, A Wilson, S Thomas-Gibson, N Suzuki, A Humphries, A Haycock, K Monahan, M Vance, A Dhillon, B Saunders
Journal: Endoscopy (2021)

Aims Advanced endoscopic imaging allows optical diagnosis of diminutive polyps. Performance thresholds for optical diagnosis have been set to allow a "resect and discard strategy" which may streamline patient care and reduce histopathology need. Aim: to assess early implementation and quality assurance of this strategy in a bowel cancer screening unit setting (1.1 million population).
Diversity and Disparities in Dementia Diagnosis and Care
Authors: Claudia H. Kawas, María M. Corrada, Rachel A. Whitmer
Journal: JAMA Neurology (2021)

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 Neurology 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 Neurology journal
Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction.
Authors: J BMichel, A LLattion, J LSalzmann, M LCerol, MPhilippe, J PCamilleri, PCorvol
Journal: Circulation Research (1988)

To explain how converting enzyme inhibition could improve the prognosis in cardiac insufficiency, the effect of converting enzyme inhibition (CEI) by S9490-3 (Perindopril) treatment for 2 months (treated infarctions, n = 18) on hormonal plasma variables and the quantitative and qualitative changes in myocardium were studied in an experimental model of left ventricular infarction in rats (untreated infarctions, n = 18) and compared to a sham-operated control group (n = 15). Induction of myocardial infarction was associated with a transient decrease in blood pressure. CEI treatment maintained a lower blood pressure throughout the experimental period. Plasma renin concentration was not significantly increased in the untreated infarct group (155.4 +/- 136.7 ng AI/ml/hr) as compared to the sham-operated group (47.6 +/- 15.9 ng AI/ml/hr). Plasma aldosterone did not change in the three experimental groups. The plasma level of immunoreactive atrial natriuretic factor increased in the untreated infarct group (185 ...
Prevention of Rh haemolytic disease.
Authors: L A Tovey, J Murray, B J Stevenson, J M Taverner
Journal: BMJ (1978)

Between 1970 and 1976 in the Yorkshire region the incidence of Rh antibodies in Rh-negative pregnant women fell by 70%. This decrease occurred in both old (long-standing) and new (first-affected) cases, which emphasised that the reduction in numbers was as much due to fewer pregnancies among Rh-negative mothers as to administration of anti-D immunoglobulin. Nevertheless, the incidence has begun to level out. The continued incidence of first-affected cases is caused by three main factors: failure of administration of anti-D immunoglobulin after normal deliveries and abortions; a steady incidence of antibodies in primigravidae; and cases in which administration of anti-D immunoglobulin had failed to protect. Administering anti-D antenatally might reduce the incidence of new cases among primigravidae who are sensitised before anti-D is normally given. Even without routine antenatal administration of anti-D, the incidence of severely affected Rh babies in the Yorkshire region could be reduced to one or two isolated cases a year in a population of three to four million by administering anti-D after all Rh-negative deliveries and after every abortion.
The conducting tissues in primitive ventricular hearts without an outlet chamber.
Authors: J LWilkinson, R HAnderson, RArnold, D IHamilton, ASmith
Journal: Circulation (1976)

We have studied the disposition of the cardiac conducting tissues in four hearts from situs solitus individuals possessing primitive ventricles without outlet chambers. These hearts correspond to the type of univentricular heart defined as common ventricle by Lev. All the hearts studied possessed normally positioned great arteries. Two groups, each consisting of two hearts, could be distinguished. The first type possessed a small posterior ridge which divided the posterior portion of the primitive ventricle into right and left ventricular sinuses. The papillary muscles to the atrioventricular valves were separate structures and arose on each side of this posterior ridge. The conducting tissues in these hearts arose from an atrioventricular node situated in the atrial septum but deviated posteriorly. The atrioventricular bundle pierced the fibrous annulus posteriorly and descended on the posterior ridge, lying to its left side. A bifurcation was not identified, and bundle branches were not present. The oth...
Transforming growth factor-beta in cardiac ontogeny and adaptation.
Authors: W RMacLellan, TBrand, M DSchneider
Journal: Circulation Research (1993)

The transforming growth factor-beta (TGF-beta) superfamily comprises a set of regulatory peptides with multiple effects on cell growth and differentiation. The elaborate regulation of TGF-beta s during embryonic development of the heart, the upregulation of TGF-beta after hemodynamic stress, and the impact of TGF-beta on cardiac gene expression together imply a prominent functional role for this family of growth factors in cardiac organogenesis and hypertrophy. Basal and TGF-beta-induced expression of skeletal alpha-actin, one of several genes specifically associated with developing or hypertrophied myocardium, each are contingent on transcriptional activation by serum response factor. A truncated form of the type II TGF-beta receptor, created by deletion of the cytoplasmic kinase domain, acts as a dominant suppressor of TGF-beta signal transduction in cultured cardiac muscle cells and may provide a suitable means to establish the functions of TGF-beta in vivo.
Pre and postoperative ventricular function in infants and children with right ventricular volume overload.
Authors: MNakazawa, J MJarmakani, M TGyepes, J VProchazka, S MYabek, R AMarks
Journal: Circulation (1977)

Hemodynamic and ventricular volume parameters were evaluated in 21 patients (24 studies) with total anomalous pulmonary venous return (TAPVR), 11 patients with secundum atrial septal defect (ASD), and eight patients who had complete correction of TAPVR or ASD. Right and left ventricular (RV and LV) volume parameters were calculated according to Simpson's rule and the area length methods, respectively. In infants with TAPVR, RV end-diastolic volume was larger than normal, but RV ejection fraction was significantly less than normal. LV end-diastolic volume and LV ejection fraction were all less than normal in infants with or without pulmonary hypertension, and the values did not correlate with the cardiorespiratory symptoms. In children with TAPVR or ASD, RV end-diastolic volume and output were higher than normal preoperatively and decreased to normal or near normal values postoperatively. The data suggest that pulmonary venous obstruction and/or RV failure are responsible for cardiorespiratory symptoms in ...
Immunohistochemical identification of arteriolar development using markers of smooth muscle differentiation. Evidence that capillary arterialization proceeds from terminal arterioles.
Authors: R JPrice, G KOwens, T CSkalak
Journal: Circulation Research (1994)

Arteriolar growth is an important event in the adaptation of normal tissues as well as in important pathologies, but the site of origin of new arterioles remains unknown. The network pattern of arteriolar development in skeletal muscle was detected by use of a new immunohistochemical technique that is based on the observation that fully differentiated (mature) vascular smooth muscle (SM) cells express both SM alpha-actin and the two myosin heavy chains (MHCs) SM-1 and SM-2, whereas less differentiated (immature) vascular SM cells do not express MHC. The anterior gracilis muscle microvasculatures of 4- and 9-week-old Sprague-Dawley rats were labeled with monoclonal antibodies to SM alpha-actin and to SM MHC. Whole transverse arteriole networks were observed, and terminal arterioles, defined as terminal segments labeled with SM alpha-actin, were classified on the basis of the presence or absence of SM MHC. A significantly different percentage of terminal arteriolar endings per network without SM MHC was obs...
Differences in the effect of metabolic inhibition on action potentials and calcium currents in endocardial and epicardial cells.
Authors: SKimura, A LBassett, TFurukawa, NFurukawa, R JMyerburg
Journal: Circulation (1991)

BACKGROUNDIschemia-induced electrophysiological changes are more prominent in epicardial cells than in endocardial cells. Epicardial action potentials shorten more than endocardial action potentials during ischemia. Since the L-type Ca2+ current plays an important role in the maintenance of action potential duration, we hypothesized that the Ca2+ current is affected more in epicardial cells than in endocardial cells during ischemia.METHODS AND RESULTSTo test this hypothesis, we examined the effect of metabolic inhibition, a major component of ischemia, on action potentials and the Ca2+ current in single cells isolated from the endocardial and epicardial layers of the feline left ventricle. The membrane voltage and current were measured by using the whole-cell mode of the patch-clamp technique. During control periods, action potentials recorded from epicardial myocytes had lower amplitude, a prominent notch between phases 1 and 2, and shorter action potential duration compared with those recorded from endo...
Cardiovascular complications during exercise training of cardiac patients.
Authors: W LHaskell
Journal: Circulation (1978)

The occurrence of major cardiovascular complications during exercise training of cardiac patients in 30 cardiac rehabilitation programs in North America was determined by questionnaire. These programs conducted medically supervised cardiac exercise classes in 103 locations and reported information on 13,570 participants who accumulated a total of 1,629,634 patient hours of supervised exercise. Cardiovascular complications were reported as nonfatal or fatal and included cardiac arrest, myocardial infarction and other. A total of 50 cardiac arrests were observed during exercise, 42 of which were successfully resuscitated while eight were fatal. Seven myocardial infarctions were reported; five were nonfatal and two were fatal. Four other fatalities were reported due to acute cardiopulmonary disorders. The average complication rate for all programs was one nonfatal and one fatal event every 34,673 and 116,402 patient hours of participation, respectively. Complication rates are lower in programs which continuo...
Abstract 16199: Timing of Aortic Valve Intervention in Patients With Severe Symptomatic Aortic Stenosis in The United States - Predictors of Delay and Relationship of Delay With Mortality
Authors: Aakriti Gupta, Maria C Alu, Martin B Leon
Journal: Circulation (2019)

Introduction: Severe symptomatic aortic stenosis (ssAS) is associated with high mortality without intervention. It is not known how time-to-treatment after symptom onset varies at the national leve...
Hormonal contraception and risk of cancer
Authors: D. Cibula, A. Gompel, A. O. Mueck, C. La Vecchia, P. C. Hannaford, S. O. Skouby, M. Zikan, L. Dusek
Journal: Human Reproduction Update (2010)

Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance.In this review, we included all cohort and case-control studies published in English up to December 2008. They were identified through a search of the literature using Pubmed and EMBASE.Data about breast cancer risk indicate a slightly increased risk among current users of oral contraceptives (OC), an effect which disappears 5-10 years after stopping. Combined OC have a significant protective effect on the risk of ovarian cancer, and the protection increases with duration of use (relative risk decreased by 20% for each 5 years of use). The significant risk reduction has been confirmed for BRCA 1 and 2 mutation carriers. The risk of endometrial cancer is reduced by about 50% in ever users, a benefit which is greater with increasing duration of use. An association has been found between increased risk of cervical cancer and long-term OC use. Current OC use has been associated with an excess risk of benign liver tumours and a modest increased risk of liver cancer. None of large prospective cohort studies with prolonged follow-up has observed an increased overall risk of cancer incidence or mortality among ever users of OC, indeed several have suggested important long-term benefits. Specifically, protective effect of OC can be used as chemoprevention in young women who are BRCA mutation carriers.Women wishing to use combined OC can be reassured that their decision is unlikely to place them at higher risk of developing cancer.
Changes in extracellular potassium activity in response to decreased pH in rabbit atrial muscle.
Authors: R BSkinner, D LKunze
Journal: Circulation Research (1976)

The extracellular and intracellular potassium (K+) activities of isolated superfused rabbit atrial muscle were measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8, intracellular K+ activity fell and extracellular K+ activity rose from a mean control level of 3.6 mM to a new steady state level of 3.9 mM after 1 hour. When the pH was further decreased to 6.1, extracellular K+ activity increased to a mean of 4.9 mM. Following the change in pH, the increase in extracellular K+ activity occurred over a period of 30-40 minutes at which time a stable value was reached and maintained for the next hour. On return to normal pH the extracellular K+ activity returned to control with a time constant of 20 minutes or less. Measurements of intracellular K+ activity over 1 hour showed a mean loss of 3 mM at pH 6.8 and a mean loss of 8 mM at pH 6.1. The loss was reversible within 20 minutes of return to control pH. The increase in extracellular ...
Aschoff bodies at necropsy in valvular heart disease. Evidence from an analysis of 543 patients over 14 years of age that rheumatic heart disease, at least anatomically, is a disease of the mitral valve.
Authors: W CRoberts, RVirmani
Journal: Circulation (1978)

Among 543 necropsy patients over age 14 years with severe chronic valvular heart disease, Aschoff bodies were found in 11 patients (2%). The ages of the 11 patients ranged from 18 to 68 years (avg. 38), and nine had had a history of acute rhematic fever earlier in life. Clinically, nine of the 11 patients had mitral stenosis with or without dysfunction of one or more other cardiac valves, one had isolated aortic regurgitation, and one had both mitral and aortic regurgitation. All 11 patients had diffuse fibrous thickening of the mitral valve leaflets, and all but one had diffuse anatomic lesions of at least one other cardiac valve. No patient with anatomic lesions limited to the aortic valve had Aschoff bodies. Thus, among patients with chronic valvular heart disease, Aschoff bodies, the only anatomic lesion pathognomonic of rheumatic heart disease, indicate diffuse anatomic lesions of the mitral leaflets and usually also anatomic lesions of one or more other cardiac valves. The functional mitral lesion i...