tbuckley/cabot-search huggingface dataset:
Effect of Diagnostic Criteria on the Prevalence of Peripheral Arterial Disease
Authors: William R. Hiatt, Sharon Hoag, Richard F. Hamman
Journal: Circulation (1995)

Background The ankle/brachial systolic blood pressure index (ABI), a noninvasive measure of peripheral arterial disease (PAD), is widely used in epidemiological studies. However, the normal ranges of the ABI in healthy populations and ABI criteria for the diagnosis of PAD in large population studies have not been critically evaluated. Methods and Results The San Luis Valley Diabetes Study (SLVDS) was designed to evaluate the prevalence and complications of non–insulin-dependent diabetes mellitus (NIDDM) in a biethnic population. The present study was conducted as part of the SLVDS to assess the prevalence of vascular disease in 1280 nondiabetic control subjects and 430 patients with NIDDM. The ABI criteria for PAD were developed in 403 healthy individuals with a low risk for cardiovascular disease. In these low-risk subjects, the average resting ABI value was 0.07 lower in women than in men. In both sexes, the dorsalis pedis ABI was 0.04 lower than in the posterior tibial artery, and the left leg ABI was 0.02 lower than the right leg ABI (all differences, P &lt;.05). In the low-risk subjects, ABI values were lower after exercise than at rest and had similar differences by sex and leg as observed at rest. Using specific abnormal cutoff points for the ABI, we evaluated three criteria for PAD in the overall population: two abnormal vessels in the same leg at rest (both dorsalis pedis and posterior tibial arteries), one abnormal vessel per leg at rest, and an ABI abnormality only after exercise. Subjects classified with PAD by the two-vessel criterion had a higher frequency of claudication and the physical finding of an absent pulse compared with subjects without PAD or patients with PAD defined by the one-vessel or exercise criterion. Use of the two-vessel criterion identified an increased risk of PAD with increasing age, NIDDM, smoking, hypertension, and elevated cholesterol levels. In contrast, the one-vessel PAD criterion was associated only with increasing age and smoking, and exercise-diagnosed PAD was not associated with any cardiovascular risk factor except for male sex. Conclusions In low-risk subjects, the normal distribution and lower abnormal cutoff point values of the ABI differed by type of test, sex, ankle vessel, and leg. When these specific abnormal cutoff points were applied to the SLVDS population, the two-vessel abnormal criterion described patients with typical clinical characteristics of PAD and the expected associations of PAD with cardiovascular risk factors. These clinical characteristics and cardiovascular risk factor associations were less evident with PAD diagnosed by the one-vessel or exercise criterion. Therefore, an abnormal dorsalis pedis and posterior tibial ABI in the same leg at rest should be used for the diagnosis of PAD in epidemiological studies.
Lack of effect of isoproterenol on unloaded velocity of sarcomere shortening in rat cardiac trabeculae.
Authors: P P de Tombe, H E ter Keurs
Journal: Circulation Research (1991)

Several recent reports have indicated that catecholamines may act directly on the crossbridge cycle, independent of intracellular calcium concentration changes. The present study investigated the effect of isoproterenol on peak force during twitches at constant sarcomere length and unloaded velocity of sarcomere shortening in isolated right ventricular trabeculae of hearts with V1 or V3 isomyosin obtained from euthyroid and hypothyroid rats, respectively. Hypothyroidism was induced by treatment of the rats with propylthiouracil for 6 weeks. Electrophoretic analysis showed that the hearts of hypothyroid animals were composed only of V3 isomyosin, whereas the hearts of euthyroid animals were composed predominantly of V1 isomyosin. Force development was measured with a silicon strain gauge and sarcomere length with laser diffraction techniques; the shortening velocity was determined from contractions in which sarcomere length was initially held constant followed by a quick release to zero load and a controlled release at zero load. Both isometric twitch force and unloaded sarcomere shortening velocity were sigmoidal functions of [Ca2+]o and of the concentration of isoproterenol. At optimal [Ca2+]o, unloaded shortening velocity was 40% lower in myocardium of hypothyroid animals than in myocardium of euthyroid animals. Isoproterenol increased the sensitivity of isometric twitch force and unloaded shortening velocity to [Ca2+]o in trabeculae from both euthyroid and hypothyroid animals. Isoproterenol did not increase unloaded shortening velocity at optimal [Ca2+]o, regardless of the thyroid state. From these results we conclude that beta-adrenergic stimulation per se does not accelerate the rate limiting step in the crossbridge cycle that determines unloaded sarcomere shortening velocity in the intact cardiac cell.
Management of isolated nonresectable liver metastases in colorectal cancer patients: a case–control study of isolated hepatic perfusion with melphalan versus systemic chemotherapy
Authors: L.B.J. van Iersel, M. Koopman, C.J.H. van de Velde, L. Mol, E.L. van Persijn van Meerten, H.H. Hartgrink, P.J.K. Kuppen, A.L. Vahrmeijer, J. W. R Nortier, R.A.E.M. Tollenaar, C. Punt, H. Gelderblom
Journal: Annals of Oncology (2010)
A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma
Authors: Abdul K Siraj, Rong Bu, Sarita Prabhakaran, Prashant Bavi, Shaham Beg, Mohsen Al Hazmi, Maha Al-Rasheed, Khadija Alobaisi, Fouad Al-Dayel, Hadeel AlManea, Nasser Al-Sanea, Shahab Uddin, Khawla S Al-Kuraya
Journal: Molecular Cancer (2014)

Recent studies emphasize the role of BRAF as a genetic marker for prediction, prognosis and risk stratification in colorectal cancer. Earlier studies have reported the incidence of BRAF mutations in the range of 5-20% in colorectal carcinomas (CRC) and are predominantly seen in the serrated adenoma-carcinoma pathway characterized by microsatellite instability (MSI-H) and hypermethylation of the MLH1 gene in the setting of the CpG island methylator phenotype (CIMP). Due to the lack of data on the true incidence of BRAF mutations in Saudi Arabia, we sought to analyze the incidence of BRAF mutations in this ethnic group. 770 CRC cases were analyzed for BRAF and KRAS mutations by direct DNA sequencing. BRAF gene mutations were seen in 2.5% (19/757) CRC analyzed and BRAF V600E somatic mutation constituted 90% (17/19) of all BRAF mutations. BRAF mutations were significantly associated with right sided tumors (p = 0.0019), MSI-H status (p = 0.0144), CIMP (p = 0.0017) and a high proliferative index of Ki67 expression (p = 0.0162). Incidence of KRAS mutations was 28.6% (216/755) and a mutual exclusivity was noted with BRAF mutations (p = 0.0518; a trend was seen). Our results highlight the low incidence of BRAF mutations and CIMP in CRC from Saudi Arabia. This could be attributed to ethnic differences and warrant further investigation to elucidate the effect of other environmental and genetic factors. These findings indirectly suggest the possibility of a higher incidence of familial hereditary colorectal cancers especially Hereditary non polyposis colorectal cancer (HNPCC) syndrome /Lynch Syndrome (LS) in Saudi Arabia.
Helicobacter pylori outer membrane proteins and gastroduodenal disease
Authors: Y Yamaoka
Journal: Gut (2005)

<b>Background and aims:</b> A number of <i>Helicobacter pylori</i> outer membrane proteins (OMPs) undergo phase variations. This study examined the relation between OMP phase variations and clinical outcome. <b>Methods:</b> Expression of <i>H pylori</i> BabA, BabB, SabA, and OipA proteins was determined by immunoblot. Multiple regression analysis was performed to determine the relation among OMP expression, clinical outcome, and mucosal histology. <b>Results:</b><i>H pylori</i> were cultured from 200 patients (80 with gastritis, 80 with duodenal ulcer (DU), and 40 with gastric cancer). The most reliable results were obtained using cultures from single colonies of low passage number. Stability of expression with passage varied with OipA &gt; BabA &gt; BabB &gt; SabA. OipA positive status was significantly associated with the presence of DU and gastric cancer, high <i>H pylori</i> density, and severe neutrophil infiltration. SabA positive status was associated with gastric cancer, intestinal metaplasia, and corpus atrophy, and negatively associated with DU and neutrophil infiltration. The Sydney system underestimated the prevalence of intestinal metaplasia/atrophy compared with systems using proximal and distal corpus biopsies. SabA expression dramatically decreased following exposure of <i>H pylori</i> to pH 5.0 for two hours. <b>Conclusions:</b> SabA expression frequently switched on or off, suggesting that SabA expression can rapidly respond to changing conditions in the stomach or in different regions of the stomach. SabA positive status was inversely related to the ability of the stomach to secrete acid, suggesting that its expression may be regulated by changes in acid secretion and/or in antigens expressed by the atrophic mucosa.
Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A
Authors: Utpal Pal, Aravinda M. de Silva, Ruth R. Montgomery, Durland Fish, Juan Anguita, John F. Anderson, Yves Lobet, Erol Fikrig
Journal: Journal of Clinical Investigation (2000)

Borrelia burgdorferi outer surface protein (Osp) A has been used as a Lyme disease vaccine that blocks transmission: OspA antibodies of immune hosts enter ticks during blood feeding and destroy spirochetes before transmission to the host can occur. B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis ticks, and many spirochetes repress OspA production during the feeding process. This preferential expression suggests that OspA may have an important function in the vector. Here we show that OspA mediates spirochete attachment to the tick gut by binding to an I. scapularis protein. The binding domains reside in the central region and COOH-terminus of OspA. OspA also binds to itself, suggesting that spirochete-spirochete interactions may further facilitate adherence in the gut. OspA-mediated attachment in the tick provides a possible mechanism for how stage-specific protein expression can contribute to pathogenesis during the B. burgdorferi natural cycle.
Prevalence of work-aggravated symptoms in clinically established asthma
Authors: K. Saarinen, A. Karjalainen, R. Martikainen, J. Uitti, L. Tammilehto, T. Klaukka, K. Kurppa
Journal: European Respiratory Journal (2003)

This population-based cross-sectional survey assessed the prevalence of work-aggravated asthma symptoms and the effect of the work environment on the aggravation of symptoms of established asthma. A questionnaire was sent to 2,613 persons (aged 20–65 yrs) with asthma. The analyses were restricted to the 969 respondents who were currently employed. The effect of occupational exposure on the aggravation of asthma symptoms at work was assessed according to both self-reported and expert-evaluated exposure. Approximately 21% of the respondents reported work-aggravated asthma symptoms at least weekly during the past month. The prevalence of those with work-aggravated symptoms increased by age, self-reported occupational exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals, and expert-evaluated probability of daily occupational exposure to airborne dusts, gases or fumes. Aggravation of asthma symptoms at work is common among employed adults with asthma. Both self-reported and expert-evaluated exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals explained the significant worsening of symptoms. The findings suggest a marked role of the work environment in the aggravation of symptoms of established asthma.
THE ROLE OF CATHETER-DIRECTED THERAPIES IN THE TREATMENT OF CONGENITAL HEART DISEASE
Authors: Jonathan J. Rome, M.D
Journal: Annual Review of Medicine (1995)

Over the past decade, transcatheter interventions have become increasingly important in the treatment of patients with congenital heart defects. These procedures may be broadly grouped as dilations (valvuloplasty, angioplasty, and endovascular stenting) or as closures (vascular embolizations and device closure of defects). Balloon valvuloplasty has become the treatment of choice for simple valvar pulmonic stenosis in all age groups and, although not curative, appears at least comparable to surgery for noncalcific aortic stenosis in newborns through young adults. Balloon angioplasty is successfully applied to a wide range of aortic, pulmonary artery, and venous stenoses. Catheter-delivered coils are used to embolize a wide range of arterial, venous, and prosthetic vascular connections. Although still investigational, devices have been successfully used for closure of large numbers of atrial and ventricular septal defects. In this review, the current role of each major catheter intervention is discussed and results are compared with alternative forms of therapy. Catheter-based therapeutics are then placed in context in a discussion of combined catheter-surgical treatment of patients with complex congenital heart defects.
EVALUATION OF SIX ENZYME IMMUNOASSAYS FOR ANTIBODY AGAINST HUMAN IMMUNODEFICIENCY VIRUS
Authors: HenkW Reesink, J.G Huisman, M Gonsalves, I.N Winkel, A.C Hekker, P.N Lelie, W Schaasberg, C Aaij, J.A.vander Does, J Desmyter, J Goudsmit
Journal: The Lancet (1986)
Sports cardiology: preventing sudden cardiac death
Authors: Jonathan A Drezner, Sanjay Sharma, Mathew G Wilson
Journal: British Journal of Sports Medicine (2014)

The sudden death of an athlete on the playing field remains one of the most striking and tragic events in sport. For the sports physician, the occurrence of an athlete in sudden cardiac arrest is both unforgettable and terrifying. Well-known cases such as Hank Gathers (1990), Marc-Vivien Foe (2003) and Fabrice Muamba (2012), provide graphic examples of an athlete enduring this deadly crisis—collapsed and unresponsive, eyes rolled back, brief myoclonic seizure-like activity and perhaps the presence of agonal respirations as limbs go from rigid to limp. For physicians responsible for the medical care of athletes, a single universal priority should guide our clinical efforts, namely to protect the health and safety of athletes. This journal once again assumes a leading role in the field of sports cardiology by presenting …
Endothelial Cells Derived From Nuclear Reprogramming
Authors: Wing Tak Wong, Ngan F. Huang, Crystal M. Botham, Nazish Sayed, John P. Cooke
Journal: Circulation Research (2012)

The endothelium plays a pivotal role in vascular homeostasis, regulating the tone of the vascular wall, and its interaction with circulating blood elements. Alterations in endothelial functions facilitate the infiltration of inflammatory cells and permit vascular smooth muscle proliferation and platelet aggregation. Therefore, endothelial dysfunction is an early event in disease processes including atherosclerosis, and because of its critical role in vascular health, the endothelium is worthy of the intense focus it has received. However, there are limitations to studying human endothelial function in vivo, or human vascular segments ex vivo. Thus, methods for endothelial cell (EC) culture have been developed and refined. Recently, methods to derive ECs from pluripotent cells have extended the scientific range of human EC studies. Pluripotent stem cells may be generated, expanded, and then differentiated into ECs for in vitro studies. Constructs for molecular imaging can also be employed to facilitate tracking these cells in vivo. Furthermore, one can generate patient-specific ECs to study the effects of genetic or epigenetic alterations on endothelial behavior. Finally, there is the opportunity to apply these cells for vascular therapy. This review focuses on the generation of ECs from stem cells; their characterization by genetic, histological, and functional studies; and their translational applications.
1,25-Dihydroxyvitamin D3 and 12-O-tetradecanoyl phorbol 13-acetate cause differential activation of Ca(2+)-dependent and Ca(2+)-independent isoforms of protein kinase C in rat colonocytes.
Authors: M Bissonnette, R K Wali, S C Hartmann, S M Niedziela, H K Roy, X Y Tien, M D Sitrin, T A Brasitus
Journal: Journal of Clinical Investigation (1995)

Considerable evidence that alterations in protein kinase C (PKC) are intimately involved in important physiologic and pathologic processes in many cells, including colonic epithelial cells, has accumulated. In this regard, phorbol esters, a class of potent PKC activators, have been found to induce a number of cellular events in normal or transformed colonocytes. In addition, our laboratory has demonstrated that the major active metabolite of vitamin D3, 1,25(OH)2D3, also rapidly (seconds-minutes) activated PKC and increased intracellular calcium in isolated rat colonocytes. These acute responses, however, were lost in vitamin D deficiency and partially restored with the in vivo repletion of 1,25(OH)2D3. The Ca(2+)-independent or novel isoforms of PKC expressed in the rat colon and the isoform-specific responses of PKC to acute treatment with phorbol esters or 1,25(OH)2D3 have not been previously characterized. Moreover, the effects of vitamin D status on PKC isoform expression, distribution, and response to agonists are also unknown. In the present experiments, in addition to PKC-alpha, rat colonocytes were found to express the novel isoforms delta, epsilon, and zeta by Western blotting using isoform-specific PKC antibodies. The tumor-promoting phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate, caused time- and concentration-dependent translocations of all these isoforms except PKC-zeta. In vitamin D deficiency, there were no alterations in colonic PKC isoform expression but significant changes in the subcellular distribution of PKC-alpha, -delta, and -zeta. Acute treatment of colonocytes from D-sufficient, but not D-deficient, rats with 1,25(OH)2D3 caused a rapid transient redistribution of only PKC-alpha from the soluble to the particulate fraction. The alterations in PKC isoform distribution and PKC-alpha responsiveness to 1,25(OH)2D3 in vitamin D deficiency were partially, but significantly, restored with 5-7 d in vivo repletion of this secosteroid. Both 12-O-tetradecanoyl phorbol 13-acetate and 1,25(OH)2D3 activated endogenous PKC, as assessed by inhibition of myristoylated alanine-rich C kinase substrate back-phosphorylation by exogenous PKC. These studies indicate that PKC-alpha, -delta, and/or -epsilon likely mediate important phorbol ester-stimulated events described in the rat colon. In contrast, PKC-alpha is implicated in the rapid (s-min) PKC-dependent events initiated by 1,25(OH)2D3 in rat colonocytes.
Variation at the <i>NFATC2</i> Locus Increases the Risk of Thiazolidinedione-Induced Edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) Study
Authors: Swneke D. Bailey, Changchun Xie, Ron Do, Alexandre Montpetit, Rafael Diaz, Viswanathan Mohan, Bernard Keavney, Salim Yusuf, Hertzel C. Gerstein, James C. Engert, Sonia Anand
Journal: Diabetes Care (2010)

OBJECTIVE Thiazolidinediones are used to treat type 2 diabetes. Their use has been associated with peripheral edema and congestive heart failure—outcomes that may have a genetic etiology. RESEARCH DESIGN AND METHODS We genotyped 4,197 participants of the multiethnic DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial with a 50k single nucleotide polymorphisms (SNP) array, which captures ∼2000 cardiovascular, inflammatory, and metabolic genes. We tested 32,088 SNPs for an association with edema among Europeans who received rosiglitazone (n = 965). RESULTS One SNP, rs6123045, in NFATC2 was significantly associated with edema (odds ratio 1.89 [95% CI 1.47–2.42]; P = 5.32 × 10−7, corrected P = 0.017). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 × 10−4) when compared with individuals homozygous for the protective allele, with heterozygous individuals having an intermediate risk. The interaction between the SNP and rosiglitazone for edema was significant (P = 7.68 × 10−3). Six SNPs in NFATC2 were significant in both Europeans and Latin Americans (P &amp;lt; 0.05). CONCLUSIONS Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone.
Diverse cellular TGF-beta 1 and TGF-beta 3 gene expression in normal human and murine lung
Authors: RK Coker, GJ Laurent, S Shahzeidi, NA Hernandez-Rodriguez, P Pantelidis, RM du Bois, PK Jeffery, RJ McAnulty
Journal: European Respiratory Journal (1996)

A role for transforming growth factor-beta 1, (TGF-beta 1) has been proposed in lung development and in the pathogenesis of pulmonary disease. However, previous studies have not delineated the cells expressing TGF-beta 1 in normal adult lung, nor compared its gene expression with that of other TGF-beta isoforms. We used digoxigenin-labelled riboprobes to localize TGF-beta 1 and TGF-beta 3 gene expression in normal adult human and mouse lung. This procedure was technically simple, providing excellent resolution. TGF-beta 1 and TGF-beta 3 messenger ribonucleic acid (mRNA) transcripts were detected in a wide variety of cells. In human lung, mRNA for both isoforms was localized to bronchiolar epithelium and alveolar macrophages. TGF-beta 1, but not TGF-beta 3 mRNA was detected in mesenchymal and endothelial cells. In murine tissue, TGF-beta 1, mRNA was localized to bronchiolar epithelium, Clara cells, mesenchymal cells, pulmonary endothelium and alveolar cells, including macrophages. TGF-beta 3 mRNA was similarly distributed but not detected in endothelium. In summary, using a nonisotopic technique in lung tissue, we have detailed the cells expressing the transforming growth factor-beta 1 and beta 3 genes in human and murine lung. There was widespread expression of these cytokines in normal lung consistent with autocrine or paracrine roles in regulating cellular turnover, immune defence and matrix protein metabolism.
8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia
Authors: Yoshiaki Chinen, Natsumi Sakamoto, Hisao Nagoshi, Tomohiko Taki, Saori Maegawa, Shotaro Tatekawa, Taku Tsukamoto, Shinsuke Mizutani, Yuji Shimura, Mio Yamamoto-Sugitani, Tsutomu Kobayashi, Yosuke Matsumoto, Shigeo Horiike, Junya Kuroda, Masafumi Taniwaki
Journal: Journal of Hematology & Oncology (2014)

The pathogenetic roles of 8q24 amplified segments in leukemic cells with double minute chromosomes remain to be verified. Through comprehensive molecular analyses of 8q24 amplicons in leukemic cells from an acute myelogenous leukemia (AML) patient and AML-derived cell line HL60 cells, we identified two novel fusion genes between NSMCE2 and long noncoding RNAs (lncRNAs), namely, PVT1-NSMCE2 and BF104016-NSMCE2. Our study suggests that 8q24 amplicons are associated with the emergence of aberrant chimeric genes between NSMCE2 and oncogenic lncRNAs, and also implicate that the chimeric genes involving lncRNAs potentially possess as-yet-unknown oncogenic functional roles.
SAFETY AND EFFICACY OF NOVEL HYPEREMIC AGENT, NICORANDIL, FOR FRACTIONAL FLOW RESERVE MEASUREMENT
Authors: Woo-Hyun Lim, Bon Kwon Koo, Chang-Wook Nam, Joon Hyung Doh, Chee Hae Kim, Ji-Hyun Jung, Jin Joo Park, Jung-kyu Han, Han-Mo Yang, Kyung Woo Park, Hyo-Soo Kim, Hiroaki Takashima, Katsuhisa Waseda, Tetsuya Amano, Daiki Kato, Akiyoshi Kurita, Young-Bae Park
Journal: Journal of the American College of Cardiology (2014)