tbuckley/cabot-search huggingface dataset:
Quantitative measurement and visual assessment of ileal Crohn's disease activity by computed tomography enterography: correlation with endoscopic severity and C reactive protein
Authors: J F Colombel, C A Solem, W J Sandborn, F Booya, E V Loftus, W S Harmsen, A R Zinsmeister, K D Bodily, J G Fletcher
Journal: Gut (2006)

Few studies have correlated computed tomography (CT) enterography findings with endoscopic severity and C reactive protein (CRP) concentrations.To examine whether small bowel inflammation at CT enterography correlates with endoscopic severity and CRP in patients with Crohn's disease (CD).CT enterography datasets from 143 CD patients undergoing ileoscopy were examined for three different CT parameters: CT bowel enhancement, as defined by the ratio of terminal ileal versus control ileal loop attenuation; vascular enlargement of the vasa recta ("the comb sign"); and mesenteric fat density. Correlations between CT scan parameters, endoscopy, and histology severity scores, and CRP were assessed using Spearman's rank correlation and logistic regression.Endoscopic score was significantly correlated with CT bowel enhancement, comb sign, and fat density (Spearman correlation coefficients 0.33-0.39; p<0.001). Correlations with histological inflammation were strongest for bowel enhancement (r = 0.34-0.38; p<0.001). CRP was elevated in patients with increased fat density versus those with increased bowel enhancement only (median 0.96 v 0.23, p = 0.002). CRP did not differ significantly between patients without evidence of active Crohn's and those with bowel enhancement and endoscopic inflammation not involving the perienteric tissues by CT (median 0.24 v 0.36; p = 0.38).Quantitative measures of bowel enhancement at CT enterography correlate with endoscopic and histological severity. CRP correlates with radiological findings of perienteric inflammation (increased fat density), but not of inflammation limited to the small bowel wall, underscoring the potential role of perienteric inflammation in CRP response in CD.
Inclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers
Authors: C. Mazouni, S.-W. Kau, D. Frye, F. Andre, H.M. Kuerer, T.A. Buchholz, W.F. Symmans, K. Anderson, K.R. Hess, A.M. Gonzalez-Angulo, G.N. Hortobagyi, A.U. Buzdar, L. Pusztai
Journal: Annals of Oncology (2007)
Attenuation of chronic hypoxic pulmonary hypertension in rats by cyclooxygenase products and by nitric oxide
Authors: P Russell, C Wright, K Kapeller, G Barer, P Howard
Journal: European Respiratory Journal (1993)

We wanted to assess the respective roles of arachidonic acid products and nitric oxide in the modulation of pulmonary hypertension in chronically hypoxic rats. In isolated blood-perfused lungs, the effects of arachidonic acid before and after treatment with the cyclooxygenase inhibitor, meclofenamate, were compared in control (C) rats and rats exposed for two weeks to 10% oxygen (chronic hypoxia CH). Arachidonic acid caused mixed dilator and constrictor effects during both normoxia and hypoxia; dilatation was more prominent in chronically hypoxic rats. Meclofenamate abolished both dilator and constrictor actions of arachidonic acid; it raised baseline, normoxic pulmonary artery pressure, in chronically hypoxic but not control rats, which suggests that dilator products of arachidonic acid are released in the pulmonary hypertension of chronic hypoxia and attenuate pulmonary artery pressure. As shown previously, the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) raised pressure in chronically hypoxic but not control rats. Meclofenamate and L-NAME given in sequence both raised pulmonary artery pressure in chronically hypoxic rats and the combined rise was substantial (+13 mmHg). We conclude that, in the conditions of our experiment, both nitric oxide and dilator prostanoids are released in hypoxic pulmonary hypertension in rats. Thus, two synthetic processes, both possibly endothelial dependent, may modulate hypoxic pulmonary hypertension.
Myocyte Enhancer Factor 2 and Class II Histone Deacetylases Control a Gender-Specific Pathway of Cardioprotection Mediated by the Estrogen Receptor
Authors: Eva van Rooij, Jens Fielitz, Lillian B. Sutherland, Victor L. Thijssen, Harry J. Crijns, Michael J. Dimaio, John Shelton, Leon J. De Windt, Joseph A. Hill, Eric N. Olson
Journal: Circulation Research (2009)

Gender differences in cardiovascular disease have long been recognized and attributed to beneficial cardiovascular actions of estrogen. Class II histone deacetylases (HDACs) act as key modulators of heart disease by repressing the activity of the myocyte enhancer factor (MEF)2 transcription factor, which promotes pathological cardiac remodeling in response to stress. Although it is proposed that HDACs additionally influence nuclear receptor signaling, the effect of class II HDACs on gender differences in cardiovascular disease remains unstudied.We aimed to examine the effect of class II HDACs on post-myocardial infarction remodeling in male and female mice.Here we show that the absence of HDAC5 or -9 in female mice protects against maladaptive remodeling following myocardial infarction, during which there is an upregulation of estrogen-responsive genes in the heart. This genetic reprogramming coincides with a pronounced increase in expression of the estrogen receptor (ER)alpha gene, which we show to be a direct MEF2 target gene. ERalpha also directly interacts with class II HDACs. Cardioprotection resulting from the absence of HDAC5 or -9 in female mice can be attributed, at least in part, to enhanced neoangiogenesis in the infarcted region via upregulation of the ER target gene vascular endothelial growth factor-a.Our results reveal a novel gender-specific pathway of cardioprotection mediated by ERalpha and its regulation by MEF2 and class II HDACs.
Cancer–testis antigen expression in triple-negative breast cancer
Authors: G. Curigliano, G. Viale, M. Ghioni, A.A. Jungbluth, V. Bagnardi, G.C. Spagnoli, A.M. Neville, F. Nolè, N. Rotmensz, A. Goldhirsch
Journal: Annals of Oncology (2010)
Comparing the long-term clinical outcome of treatment with methotrexate or sulfasalazine prescribed as the first disease-modifying antirheumatic drug in patients with inflammatory polyarthritis
Authors: S L Hider, A Silman, D Bunn, S Manning, D Symmons, M Lunt
Journal: Annals of the Rheumatic Diseases (2006)

To compare the clinical and functional outcome at 2 and 5 years in patients with inflammatory polyarthritis treated with either methotrexate (MTX) or sulfasalazine (SSZ) as the first disease-modifying antirheumatic drug (DMARD).Patients recruited to a primary-care-based inception cohort of patients with inflammatory polyarthritis were eligible for this analysis if they were started on either SSZ (n = 331) or MTX (n = 108) as their first DMARD within 3 months. Outcomes assessed included the Disease Activity Score (DAS)28, Health Assessment Questionnaire, radiological erosions (Larsen Score) and cumulative mortality with the proportions still on the original treatment. To overcome potential bias in allocation to these two treatments, a propensity score was calculated based on baseline disease status variables.are expressed as the mean difference between MTX and SSZ, both unadjusted and adjusted for propensity score.The baseline differences between the two groups disappeared after adjusting for propensity score. At 2 and 5 years there were few differences in the clinical outcomes, either unadjusted or after adjustment for propensity. By contrast, at 5 years the proportion that was erosive was lower in the MTX group: odds ratio 0.3 (95% confidence interval 0.1 to 0.8), with a 31% lower Larsen Score after adjustment. At both time points, those treated with MTX were at least twice as likely to remain on that drug as those treated with SSZ.Long-term clinical outcome is similar in patients prescribed MTX and SSZ, although it would seem that MTX has greater potential to suppress erosions, which supports it being the first DMARD of choice.
Plaque distribution and vascular remodeling of ruptured and nonruptured coronary plaques in the same vessel: an intravascular ultrasound study in vivo
Authors: Clemens von Birgelen, Wolfgang Klinkhart, Gary S Mintz, Alexandra Papatheodorou, Jörg Herrmann, Dietrich Baumgart, Michael Haude, Heinrich Wieneke, Junbo Ge, Raimund Erbel
Journal: Journal of the American College of Cardiology (2001)
Effects of Selective Inhibitors of Nitric Oxide Synthase-2 Dimerization on Acute Cardiac Allograft Rejection
Authors: Matthias J. Szabolcs, Ji Sun, Ningsheng Ma, Arline Albala, Robert R. Sciacca, Gary B. Philips, John Parkinson, Niloo Edwards, Paul J. Cannon
Journal: Circulation (2002)

Nitric oxide synthase-2 (NOS2) is expressed during acute cardiac allograft rejection in association with myocardial inflammation, contractile dysfunction, and death of cardiomyocytes by necrosis and apoptosis. Recently, allosteric inhibitors of NOS2 monomer dimerization that block NOS2 activity have been developed.To investigate effects of selective NOS2 blockade, 15 mg/kg of BBS-1 or BBS-2 was administered twice daily subcutaneously to rats starting the day of heterotopic heart transplantation. Cardiac allograft survival was increased significantly, from 6.8 days in controls to 13.3 and to 14.2 days in NOS2-inhibited allografts. At day 5 after heart transplantation, synthesis of NOx was reduced by 53%. There were significantly fewer T lymphocytes and macrophages in the inflammatory infiltrate, as well as less edema and cardiomyocyte damage, and the International Society of Heart and Lung Transplantation score fell from 5 to 4 and 3.5. NOS2 and nitrotyrosine immunostaining and the mean numbers of apoptotic cells and of apoptotic cardiomyocytes were significantly diminished in the treated allografts.The data indicate that selective inhibition of NOS2 dimerization prolongs survival and reduces myocardial inflammation and cardiomyocyte damage in acute cardiac allograft rejection.
Miniaturized Oligonucleotide Arrays
Authors: Albert Sotto, Jean-Louis Richard, Nathalie Jourdan, Christophe Combescure, Nicole Bouziges, Jean-Philippe Lavigne
Journal: Diabetes Care (2007)

We sought to evaluate the use of oligonucleotide arrays to discriminate colonization from infection due to Staphylococcus aureus in diabetic foot ulcers.We included diabetic patients hospitalized in a diabetic foot department for an episode of foot ulcer. Only patients who had no antibiotic treatment during the previous 6 months were included. At admission, ulcers were classified on clinical examination, according to the Infectious Diseases Society of America system. Seventy-two patients with a culture positive only for S. aureus as the sole pathogen were included. In individuals with a grade 1 ulcer, a second wound bacterial specimen was obtained 1 month later. Using oligonucleotide arrays, S. aureus resistance and virulence genes were compared between grade 1 and grades 2-4 ulcers.S. aureus was initially isolated from 22 grade 1 and 50 grade 2-4 ulcers: 35 were methicillin resistant and 37 methicillin sensitive. In 20 grade 1 ulcers (92%), no virulence genes were identified, whereas these genes were present in all but 1 grade 2-4 ulcers. During follow-up, the two grade 1 ulcers that were infected with strains carrying virulence genes rapidly deteriorated; the array technology showed unchanged genotype profiles. On the contrary, two grade 1 ulcers healed: the genotype profiles were different from those at inclusion but without appearance of virulence genes.The DNA array appears as a promising technique and is easy to perform. Our observational study suggests that it might help distinguish colonized grade 1 from infected grade 2 wounds, predict ulcer outcome, and contribute to a more adequate use of antibiotics.
A Cross-Sectional Study of the Effects of Type 2 Diabetes and Other Cardiovascular Risk Factors on Structure and Function of Nonstenotic Arteries of the Lower Limb
Authors: David N. O’Neal, George Dragicevic, Kevin G. Rowley, Mohamed Z. Ansari, Nicholas Balazs, Alicia Jenkins, James D. Best
Journal: Diabetes Care (2003)

OBJECTIVE—To compare intimal-medial thickness (IMT) and pulse wave conduction velocity (PWCV) in unstenosed arteries of the lower limb in subjects with and without type 2 diabetes and to determine the contribution of a range of cardiovascular risk factors. RESEARCH DESIGN AND METHODS—IMT and PWCV were determined in lower-limb arteries of 79 subjects with diabetes and 77 euglycemic subjects. Plasma lipids were determined by enzymatic assays, and LDL particle size was measured by gradient gel electrophoresis. Lag time for copper-induced oxidation of LDL was determined. α-Tocopherol, retinol, and ascorbate levels were determined by high-performance liquid chromatography, soluble E-selectin by enzyme-linked immunosorbent assay, and fibrinogen and factor VII by automated assays. RESULTS—Subjects with diabetes had greater superficial femoral artery (SFA) IMT, popliteal artery (PA) IMT, and SFA PWCV (all P &amp;lt; 0.0001). In univariate analysis, IMT and PWCV correlated with increased waist-to-hip ratio, triglycerides, and fibrinogen and inversely with HDL cholesterol and LDL size. Ascorbate was inversely associated with IMT, and LDL lag time was inversely correlated with PWCV. Subjects with the greatest number of features of the metabolic syndrome had the highest IMT and PWCV. CONCLUSIONS—Adverse changes in the structure and function of unstenosed lower-limb arteries are present in type 2 diabetes and are associated with features of the metabolic syndrome.
Imaging the joint and enthesis: insights into pathogenesis of psoriatic arthritis
Authors: D McGonagle
Journal: Annals of the Rheumatic Diseases (2005)

The distinct radiographic features of psoriatic arthritis (PsA) help confirm it as a distinct entity from rheumatoid arthritis and highlight some unique non-synovial based disease imaging features. The advent of magnetic resonance imaging and a better understanding of joint microanatomy including the complexity of joint entheses provide a unifying anatomical and biomechanical concept that links disease at the apparently disparate sites of involvement in PsA, including the synovium, the enthesis, the bone and the periosteum. These findings suggest a reason for the localisation of disease to skeletal sites that are subject to repeated mechanical stressing.
P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries
Authors: Patrick André, Suzanne M. Delaney, Thomas LaRocca, Diana Vincent, Francis DeGuzman, Marzena Jurek, Beverley Koller, David R. Phillips, Pamela B. Conley
Journal: Journal of Clinical Investigation (2003)

The critical role for ADP in arterial thrombogenesis was established by the clinical success of P2Y12 antagonists, currently used at doses that block 40–50% of the P2Y12 on platelets. This study was designed to determine the role of P2Y12 in platelet thrombosis and how its complete absence affects the thrombotic process. P2Y12-null mice were generated by a gene-targeting strategy. Using an in vivo mesenteric artery injury model and real-time continuous analysis of the thrombotic process, we observed that the time for appearance of first thrombus was delayed and that only small, unstable thrombi formed in P2Y12–/– mice without reaching occlusive size, in the absence of aspirin. Platelet adhesion to vWF was impaired in P2Y12–/– platelets. While adhesion to fibrinogen and collagen appeared normal, the platelets in thrombi from P2Y12–/– mice on collagen were less dense and less activated than their WT counterparts. P2Y12–/– platelet activation was also reduced in response to ADP or a PAR-4–activating peptide. Thus, P2Y12 is involved in several key steps of thrombosis: platelet adhesion/activation, thrombus growth, and stability. The data suggest that more aggressive strategies of P2Y12 antagonism will be antithrombotic without the requirement of aspirin cotherapy and may provide benefits even to the aspirin-nonresponder population.
Temporal arteritis in a large necropsy series.
Authors: G Ostberg
Journal: Annals of the Rheumatic Diseases (1971)

Temporal arteritis is a disease of old age, often manifesting itself clinically with rather vague symptoms of fatigue, general malaise, and weight loss.The characteristic headache or symptoms from the temporal regions may appear late (Harrison and Bevan, 1967) or may pass unobserved.The first report of a case was given by Hutchinson (1890) in London, and series of varying numbers have since been published from different parts of the world.Most have been collected in more or less specialized clinics and there has been no correlation with any defined population.The number of reports shows that the condition is not rare.The present investigation establishes the pre- valence of temporal arteritis in a necropsy series from a defined population, namely the city of Malm6 in Southern Sweden.Discussion with Dr. Hamrin* of Vaxjo, who is investigating poly- myalgia rheumatica and temporal arteritis in a county of southern Sweden, gave the impression that there may be differences between the urban and rural districts.As Vaxjo has no regular pathology service, contact was established with the pathology department in the nearby county of Kalmar. MaterialsThe present series included all adult subjects coming to necropsy in Malmo General Hospital (1,097 cases) between December 1, 1962, and November 30, 1963.The city of Malmo has about 250,000 inhabitants.There is only one general hospital, which includes a department for chronic diseases.About 65 per cent. of all deaths in the town occur in hospital and 98 to 99 per cent. of all patients who die there are subjected to post mortem examination.The age distribution of the Malmo series is given in Fig. 1.The frequency of necrop- sies in the town population is somewhat higher for young subjects and lower for older subjects (IBerge, 1967).Cases were also collected from the Kalmar hospital between January 1 and December 31, 1963.The com-
Stimulation of Renin Secretion by Angiotensin II Blockade is Gsα-Dependent
Authors: Limeng Chen, Soo Mi Kim, Christoph Eisner, Mona Oppermann, Yuning Huang, Diane Mizel, Lingli Li, Min Chen, Maria Luisa Sequeira Lopez, Lee S. Weinstein, Roberto A. Gomez, Jurgen Schnermann, Josephine P. Briggs
Journal: Journal of the American Society of Nephrology (2010)

Angiotensin II converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) presumably stimulate renin secretion by interrupting angiotensin II feedback inhibition. The increase in cytosolic calcium caused by activation of Gq-coupled AT1 receptors may mediate the renin-inhibitory effect of angiotensin II at the cellular level, implying that ACEI and ARB may work by reducing intracellular calcium. Here, we investigated whether angiotensin II blockade acts predominantly through Gs-mediated stimulation of adenylyl cyclase (AC) by testing the effect of ACEI and ARB in mice with juxtaglomerular cell-specific deficiency of the AC-stimulatory Gsα. The ACEI captopril and quinaprilate and the ARB candesartan significantly increased plasma renin concentration (PRC) to 20 to 40 times basal PRC in wild-type mice but did not significantly alter PRC in Gsα-deficient mice. Captopril also completely abrogated renin stimulation in wild-type mice after co-administration of propranolol, indomethacin, and L-NAME. Treatment with enalapril and a low-NaCl diet for 7 days led to a 35-fold increase in PRC among wild-type mice but no significant change in PRC among Gsα-deficient mice. Three different pharmacologic inhibitors of AC reduced the stimulatory effect of captopril by 70% to 80%. In conclusion, blockade of angiotensin II stimulates renin synthesis and release indirectly through the action of ligands that activate the cAMP/PKA pathway in a Gsα-dependent fashion, including catecholamines, prostaglandins, and nitric oxide.
Carcinoembryonic Antigen Messenger RNA Expression in Blood Predicts Recurrence in Esophageal Cancer
Authors: Tetsuro Setoyama, Shoji Natsugoe, Hiroshi Okumura, Masataka Matsumoto, Yasuto Uchikado, Sumiya Ishigami, Tetsuhiro Owaki, Sonshin Takao, Takashi Aikou
Journal: Clinical Cancer Research (2006)

The clinical significance of isolated tumor cells (ITC) in blood has not been clearly established, particularly during follow-up in cancer patients. We conducted a longitudinal analysis of the relationship between ITC in blood during follow-up and clinicopathologic findings in patients with esophageal squamous cell carcinoma.Blood samples obtained from 106 patients were examined by real-time RT-PCR assay targeting carcinoembryonic antigen (CEA) mRNA. Follow-up examination every 3 months after surgery included testing for CEA mRNA and tumor markers, as well as imaging.Thirty-nine (36.8%) patients were positive for CEA mRNA expression. CEA mRNA positivity significantly correlated with tumor depth, lymph node metastasis, stage, and venous invasion. Recurrent disease was found in 34 of 106 (32.1%) cases. CEA mRNA was found in 28 (76.5%) patients experiencing relapse. Of these 28 patients, the number positive of CEA mRNA before detection by imaging, at the same time of detection by imaging, and after detection by imaging was 18 (52.9%), 8 (23.5%), and 2 (5.9%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for CEA mRNA were higher than those for serum CEA or squamous cell carcinoma. Patients positive for CEA mRNA experienced significantly shorter disease-free interval than those with negative CEA mRNA (P < 0.001). According to multivariate analysis, CEA mRNA positivity was an independent factor for disease-free interval.Examination of CEA mRNA in peripheral blood during follow-up is useful for early detection of occult recurrence. We believe that CEA mRNA in blood will be a new marker for recurrence in esophageal squamous cell carcinoma.