tbuckley/cabot-search huggingface dataset:
Ribozyme-Mediated Inhibition of Expression of Leukocyte-type 12-Lipoxygenase in Porcine Aortic Vascular Smooth Muscle Cells
Authors: Jia-Li Gu, Dange Veerapanane, John Rossi, Rama Natarajan, Lisa Thomas, Jerry Nadler
Journal: Circulation Research (1995)

Abstract Activation of a leukocyte-type 12-lipoxygenase (12-LO) has been proposed to be an important mechanism for angiotensin II– and glucose-induced vascular smooth muscle cell growth. Currently, no specific pharmacological inhibitors for the leukocyte-type 12-LO are available to test this hypothesis. We have therefore designed a chimeric DNA-RNA hammerhead ribozyme to produce cleavage at the first GUC sequence at nucleotide 7 of porcine leukocyte 12-LO mRNA. The ribozyme was tested in vitro with a 206-base 12-LO mRNA as substrate. We observed that the ribozyme specifically and dose-dependently cleaved porcine leukocyte 12-LO mRNA at the predicted site under physiological temperature. Furthermore, we also efficiently delivered the ribozyme into porcine aortic vascular smooth muscle cells by transfection with cationic liposomes. The ribozyme caused a dose-dependent decrease in levels of porcine leukocyte-type 12-LO mRNA in these cells and was more potent than an antisense oligonucleotide directed against porcine leukocyte 12-LO. The 12-LO ribozyme also attenuated 12-LO protein levels in the cells. The action of the ribozyme was primarily a result of its catalytic activity, since a modified ribozyme that lacks catalytic activity showed reduced effects. This represents the first ribozyme directed against a mammalian LO pathway. These results demonstrate the potential utility of new ribozyme technology to generate novel agents for gene modulation experiments to modify the development or progression of vascular disease in humans.
Identification of Periplakin as a New Target for Autoreactivity in Idiopathic Pulmonary Fibrosis
Authors: Camille Taillé, Sabine Grootenboer-Mignot, Céline Boursier, Laurence Michel, Marie-Pierre Debray, Jérôme Fagart, Lorena Barrientos, Arnaud Mailleux, Natacha Cigna, Florence Tubach, Joëlle Marchal-Sommé, Paul Soler, Sylvie Chollet-Martin, Bruno Crestani
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Injury to alveolar epithelial cells is central to the pathophysiology of idiopathic pulmonary fibrosis (IPF). An abnormal autoimmune response directed against antigens of the alveolar epithelium may contribute to the disease.To detect circulating autoantibodies (autoAbs) directed against epithelial structures.We performed immunoblot by separating human placental amnion extract or alveolar epithelial cell (A549 cell line) proteins on polyacrylamide gels, blotting on nitrocellulose membranes, and incubating with serum from patients with IPF (n = 40) or healthy subjects (n = 40). Proteomic analysis and mass spectrometry characterized the target protein. Inhibition experiments performed with the correspondent recombinant protein confirmed our results.We identified IgG autoAbs recognizing a 200-kD protein in the serum of patients with IPF. Proteomic analysis identified this protein as human periplakin (PPL), a component of desmosomes. Anti-PPL Abs were found by immunoblot in both serum and bronchoalveolar lavage in patients with IPF: 16/40 (40%) of them were positive versus none of the control subjects. Immunohistochemistry revealed that PPL was strongly expressed in bronchial and alveolar epithelium, but that PPL exhibited changes in intracellular localization among normal and fibrotic alveolar epithelium. In an alveolar epithelial wound repair assay, an anti-PPL IgG decreased cell migration. Recombinant PPL induced bronchoalveolar lavage T lymphocyte proliferation. Patients with IPF with anti-PPL Abs had a more severe respiratory disease, despite no difference in survival.We found a new circulating autoAb directed against PPL in patients with IPF, associated with a more severe disease.
TNM Staging of Cancers of the Head and Neck: Striving for Uniformity Among Diversity
Authors: S. G. Patel, J. P. Shah
Journal: CA A Cancer Journal for Clinicians (2005)

The sixth edition of the tumor-node-metastasis staging system for head and neck cancers incorporates some significant shifts in philosophy. As treatment paradigms shift and data from ongoing clinical and basic research become available, further revisions may be expected in the future. The purpose of this review is to highlight the complexities involved in developing a user-friendly staging system and to report the major changes in the new version. The authors also discuss some areas of current interest that may have the potential to lead to future modifications.
Adiponectin and signal pathways in obesity-induced colon cancer
Authors: Huang Xf, Chen J
Journal: Gut (2009)

Obesity is reaching epidemic levels worldwide. Incidence rates of many types of cancers including colon cancer, the fourth most common cancer type, are increased substantially in obese individuals. Many known risk factors for colorectal cancer development are altered in obesity, including increased blood levels of insulin, insulin-like growth factor (IGF), leptin, interleukin 6 (IL6), tumour necrosis factor α (TNFα) and a decreased blood level of adiponectin (table 1). These risk factors can, in turn, activate intracellular signal pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and RhoA, which play an important role in the carcinogenesis …
Probe tip contact force and bowel distension affect crypt morphology during confocal endomicroscopy
Authors: R. C. Newton, D. Noonan, C. Payne, J. Andreyev, A. Di Marco, M. V. Scarzanella, A. Darzi, G.-Z. Yang
Journal: Gut (2011)

<h3>Introduction</h3> Endoscopic probe-based confocal endomicroscopy (pCLE) provides 500 μm diameter <i>en-face</i>, cellular resolution, 'optical biopsies' of the gastrointestinal mucosal surface. Many burgeoning classification criteria incorporate crypt morphology analysis: hyperplastic colonic polyps display 'star-shaped' crypt openings; ulcerative colitis features enlarged crypt openings with increased intercryptal separation.1 We hypothesised that pCLE probe tip contact force and bowel distension may affect crypt morphology independently. <h3>Methods</h3> For the <i>ex-vivo</i> force study, still pCLE images were acquired of 3 × 3 cm pieces of porcine colon applied with topical 0.02% acriflavine. A rig vertically suspended the bowel against a compressible surface. A 2.5 mm diameter pCLE probe, clamped to a force-sensitive linear servo mechanism was driven perpendicularly into fresh tissue regions until a contact force of 0.005, 0.05, 0.1, or 0.5 N was achieved. 20 images were analysed for each force. For the in vivo bowel distension study, in an anaesthetised 70 kg pig using intravenous fluorescein 10%, 20 representative stills were analysed from each of 2-min endoscopic pCLE video loops with gentle probe contact against sigmoid (A) collapsed, (B) inflated to 4 cm diameter and (C) hyperinflated to 6 cm diameter using a proximal bowel clamp. <h3>Results</h3> In the ex vivo study, as the probe contact force increased, the crypts appeared to be squeezed out of the field of view, and the mean visible crypt number per image decreased: 16.8 (±3.1) at 0.005N, 9.5 (±1.4) at 0.05N, 8.3 (±1.4) at 0.1N and 5.7 (±1.4) at 0.5N. Furthermore, the mean crypt diameter increased according to contact force: 46 μm (±11) at 0.005N, 61 μm (±18) at 0.05N, 74 μm (±16) at 0.1N and 89 μm (±27) at 0.5N. In the sigmoidoscopy study, for collapsed, inflated and hyperinflated sigmoid colon respectively, the mean number of visible crypts decreased: 23.7 (±3.1), 14.0 ((±2.1) and 8.1(±0.7). Similarly, the mean crypt diameter increased: 65.4 μm (±2.2), 85 μm (±2.1) and 95.6 μm (±2.8). <h3>Conclusion</h3> Both increasing pCLE probe tip contact force and bowel distension reduce the number of visible crypts per field of view, and increase the mean crypt diameter. This may have important implications for standardising image acquisition protocol during endoscopic pCLE to ensure morphological alterations to crypts can be exclusively attributed to tissue differences.
Daily physical activity in subjects with newly diagnosed COPD
Authors: Hans Van Remoortel, Miek Hornikx, Heleen Demeyer, Daniel Langer, Chris Burtin, Marc Decramer, Rik Gosselink, Wim Janssens, Thierry Troosters
Journal: Thorax (2013)

<h3>Rationale</h3> Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce. This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD. <h3>Methods</h3> Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male). PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry. Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics. <h3>Results</h3> PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27–120) vs 110 (55–164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p&lt;0.05). Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (T<sub>L</sub>,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO<sub>2</sub> peak) had significantly lower PA. Multiple regression analysis identified 6 MWD and T<sub>L</sub>,co as independent predictors of PA in COPD. <h3>Conclusions</h3> The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD. Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.
Outcomes of Urgent Warfarin Reversal With Frozen Plasma Versus Prothrombin Complex Concentrate in the Emergency Department
Authors: Michael Hickey, Mathieu Gatien, Monica Taljaard, Amiirah Aujnarain, Antonio Giulivi, Jeffrey J. Perry
Journal: Circulation (2013)

Physicians reverse patients' warfarin anticoagulation with frozen plasma or prothrombin complex concentrate. Our objective was to determine adverse event frequency after urgent reversal with frozen plasma versus the prothrombin complex concentrate Octaplex.This natural before-after retrospective cohort study in 2 tertiary care emergency departments compared anticoagulation reversal with frozen plasma (September 2006-August 2008) and with Octaplex (September 2008-August 2010), without other system changes. We included adult patients on warfarin with an international normalized ratio ≥1.5 who received frozen plasma or Octaplex. Our primary outcome was serious adverse events (death, ischemic stroke, myocardial infarction, heart failure, venous thromboembolism, or peripheral arterial thromboembolism) within 7 days. Secondary outcomes included time to international normalized ratio reversal, hospital length of stay, and red blood cells transfused within 48 hours. We included 149 patients receiving frozen plasma and 165 receiving Octaplex. The incidence of serious adverse events for the frozen plasma group was 19.5% compared with 9.7% for the Octaplex group (P=0.014; relative risk, 2.0; 95% confidence interval, 1.1-3.5). This remained significant after adjustment for baseline history and reason for treatment (P=0.038; adjusted relative risk, 1.85; 95% confidence interval, 1.03-3.3) in multivariable regression analysis. Median international normalized ratio reversal was 11.8 hours with frozen plasma and 5.7 hours with Octaplex (P<0.0001). Mean red cell transfusion was 3.2 with frozen plasma and 1.4 with Octaplex (P<0.0001).Octaplex for urgent reversal of warfarin resulted in faster reversal and lower red cell transfusion requirement with fewer adverse events than frozen plasma.
Anticardiolipin antibodies and recurrent early pregnancy loss: a century of equivocal evidence
Authors: Christine A. Clark, Carl A. Laskin, Karen A. Spitzer
Journal: Human Reproduction Update (2012)

In 1987, Nigel Harris cautioned against over-diagnosing the antiphospholipid syndrome (APS). In what was a rather prophetic editorial titled 'The Syndrome of the Black Swan', he suggested that while patients with APS do indeed exist, they are probably much more unusual than many medical professionals might like to believe. He expressed concern that the value of studying antiphospholipid antibodies (aPLs) as interesting non-organ specific autoantibodies, would become lost in a 'sea of over-interpreted and over-reported laboratory and clinical findings'. It is our contention that 25 years later, this prediction has come to pass, particularly with respect to one type of aPL and its relation to a clinical event, namely anticardiolipin antibodies and early recurrent pregnancy loss. In this commentary, we trace the evolution of the current dogma and propose that reevaluation of available data from an alternative perspective results in quite a different understanding, the acceptance of which would necessitate not only a revision of the classification criteria for APS but also the subsequent revision of many diagnoses.
Effects of weight loss in obese subjects with normal fasting plasma glucose or impaired glucose tolerance on insulin release and insulin resistance according to a minimal model analysis
Authors: Yuriko Yoshida, Naotake Hashimoto, Yoshiharu Tokuyama, Hiroshi Kitagawa, Kazuo Takahashi, Kazuo Yagui, Azuma Kanatsuka, Hideaki Bujo, Mayumi Higurashi, Saori Miyazawa, Shouji Yoshida, Yasushi Saito
Journal: Metabolism (2004)
How Sociodemographics, Presence of Oncology Specialists, and Hospital Cancer Programs Affect Accrual to Cancer Treatment Trials
Authors: Warren B. Sateren, Edward L. Trimble, Jeffrey Abrams, Otis Brawley, Nancy Breen, Leslie Ford, Mary McCabe, Richard Kaplan, Malcolm Smith, Richard Ungerleider, Michaele C. Christian
Journal: Journal of Clinical Oncology (2002)

We chose to examine the impact of socioeconomic factors on accrual to National Cancer Institute (NCI)-sponsored cancer treatment trials.We estimated the geographic and demographic cancer burden in the United States and then identified 24,332 patients accrued to NCI-sponsored cancer treatment trials during a 12-month period. Next, we examined accrual by age, sex, geographic residence, health insurance status, health maintenance organization market penetration, several proxy measures of socioeconomic status, the availability of an oncologist, and the presence of a hospital with an approved multidisciplinary cancer program.Pediatric patients were accrued to clinical trials at high levels, whereas after adolescence, only a small percentage of cancer patients were enrolled onto clinical trials. There were few differences by sex. Black males as well as Asian-American and Hispanic adults were accrued to clinical trials at lower rates than white cancer patients of the same age. Overall, the highest observed accrual was in suburban counties. Compared with the United States population, patients enrolled onto clinical trials were significantly less likely to be uninsured and more like to have Medicare health insurance. Geographic areas with higher socioeconomic levels had higher levels of clinical trial accruals. The number of oncologists and the presence of approved cancer programs both were significantly associated with increased accrual to clinical trials.We must work to increase the number of adults who enroll onto trials, especially among the elderly. Ongoing partnership with professional societies may be an effective approach to strengthen accrual to clinical trials.
Mutations of CpG dinucleotides located in the triiodothyronine (T3)-binding domain of the thyroid hormone receptor (TR) beta gene that appears to be devoid of natural mutations may not be detected because they are unlikely to produce the clinical phenotype of resistance to thyroid hormone.
Authors: Y Hayashi, T Sunthornthepvarakul, S Refetoff
Journal: Journal of Clinical Investigation (1994)

Thyroid hormone receptor (TR) beta gene mutations identified in patients with resistance to thyroid hormone (RTH) revealed two clusters ("hot" areas) of mutations (RTHmut) in the triiodothyronine (T3)-binding domain. Furthermore, 45% of RTHmuts and 90% of recurring mutations are located in CpG dinucleotides ("hot spots"). To investigate why the region between the two hot areas lacks RTHmuts, we produced 10 artificial mutant TR beta s (ARTmut) in this "cold" region according to the hot spot rule (C-->T or G-->A substitutions in CpGs). The properties of ARTmuts were compared with those of six RTHmuts. Among all RTHmuts, R320H manifesting a mild form of RTH showed the least impairment of T3-binding affinity (Ka). In contrast, Ka was normal in six ARTmuts (group A), reduced to a lesser extent than R320H in three (group B), and one that was truncated (R410X) did not bind T3. All RTHmuts had impaired ability to transactivate T3-responsive elements and exhibited a strong dominant negative effect on cotransfected wild-type TR beta. Group B and A ARTmuts had minimally impaired or normal transactivation and weak or no dominant negative effect, respectively. R410X showed neither transactivation nor dominant negative effect. Natural mutations expected to occur in the cold region of TR beta should fail to manifest as RTH (group A) or should escape detection (group B) since the serum thyroid hormone levels required to compensate for the reduced binding affinity should be inferior to those found in subjects with R320H. R410X would manifest RTH only in the homozygote state. The cold region of the putative T3-binding domain is relatively insensitive to amino acid changes and, thus, may not be involved in a direct interaction with T3.
IDIBELL Cancer Conference on Metastasis and Angiogenesis
Authors: F. Javier Carmona, Manel Esteller
Journal: Cancer Research (2011)

The IDIBELL Cancer Conference (ICC) on Metastasis and Angiogenesis was held in Barcelona, Spain, on May 26-27, 2011. The program content was developed by Dr. Manel Esteller, director of the Cancer Epigenetics and Biology Program (PEBC-IDIBELL), Dr. Oriol Casanovas and Dr. Francesc Viñals Canals of the Catalan Institute of Oncology (ICO-IDIBELL), and Dr. Danny R. Welch from the University of Kansas Cancer Center. The topics discussed during the meeting included the latest advances in epigenetic control of metastasis and tumor cell invasion, and molecular mechanisms of angiogenesis and tumoral angiogenesis, and were presented by invited keynote speakers. One issue that recurred throughout the meeting was the increased appreciation of tumor-stromal/microenvironment interactions and how the tumor cells respond to these signals in the cancer dissemination process.
Improved lipid profile and reduced lipid peroxidation with soy milk in patients with primary hypercholesterolemia
Authors: Liliana Bricarello, Francisco A. Fonseca, Marcelo C. Bertolami, Andre Faludi, Nelson Kasinski, Leonor E. Pinto, Waldir G. Relvas, Maria C. Izar, Silvia S. Ihara, Antonio C. Carvalho
Journal: Journal of the American College of Cardiology (2003)
Mortality Study of Canadian Male Farm Operators: Non-Hodgkin's Lymphoma Mortality and Agricultural Practices in Saskatchewan
Authors: D. T. Wigle, R. M. Semenciw, K. Wilkins, D. Riedel, L. Ritter, H. I. Morrison, Y. Mao
Journal: JNCI Journal of the National Cancer Institute (1990)

A cohort study of the mortality experience (1971-1985) of male Saskatchewan farmers has been conducted. This study involved linkage of records of the almost 70,000 male farmers identified on the 1971 Census of Agriculture and the corresponding Census of Population to mortality records. Pesticide exposure indices for individual farm operators for the year 1970 were derived from the 1971 Census of Agriculture records. Although the cohort as a whole had no excess mortality for any specific causes of death, including non-Hodgkin's lymphoma, significant dose-response relationships were noted between risk of non-Hodgkin's lymphoma and acres sprayed in 1970 with herbicides, as well as with dollars spent on fuel and oil for farm purposes in 1970. Using Poisson regression modeling, we found that relative risks for the highest level of herbicide use (greater than or equal to 250 acres sprayed) and fuel purchased in 1970 (greater than or equal to $900) on farms less than 1,000 acres total area were 2.2 (95% confidence interval = 1.0-4.6) and 2.3 (95% confidence interval = 1.1-4.7), respectively.
THE HEPATIC BLOOD FLOW AND SPLANCHNIC OXYGEN CONSUMPTION OF MAN—THEIR ESTIMATION FROM UREA PRODUCTION OR BROMSULPHALEIN EXCRETION DURING CATHETERIZATION OF THE HEPATIC VEINS 1
Authors: J. D. Myers
Journal: Journal of Clinical Investigation (1947)

The hepatic blood flow was first estimated in normal man by Bradley, Ingelfinger, Bradley and Curry (1).Before applying this bromsulphalein procedure to clinical problems, it seemed advisable not only to confirm their measurements but to esti- mate hepatic blood flow by a fundamentally differ- ent method.The urea method for hepatic blood flow, worked out in the dog by Lipscomb and Crandall (2), has been adapted to normal un- anesthetized human subjects.The hepatic venous- arterial oxygen difference, total oxygen consump- tion, and cardiac output have been measured in the same subjects.By multiplying the hepatic vein flow by the hepatic venous-arterial oxygen difference, one obtains an estimate of the splanch- nic oxygen consumption.2The oxygen consumption and blood flow of the brain and kidney have been estimated by other investigators.Thus, the measurement of oxygen consumption and blood flow of the splanchnic area allows one to construct a fairly complete picture of the degree of oxygen utilization by and the blood flow through the most important areas of the body.Urea, among the various metabolites involving the liver, has several attributes which adapt it as a test substance for the estimation of liver blood flow.As far as is known, urea is produced in the human organism only by the liver (3, 4) and, once formed, is not converted to other compounds.Urea is very diffusible not only through the vari-