tbuckley/cabot-search huggingface dataset:
Endothelial cells modulate eosinophil surface markers and mediator release
Authors: M-J. Dallaire, C. Ferland, N. Pagé, S. Lavigne, F. Davoine, M. Laviolette
Journal: European Respiratory Journal (2003)

Migration from blood to tissue modulates eosinophil function, possibly through interactions with endothelial cells. The effects of contact with and migration through endothelial cells on eosinophil expression of surface markers and release of leukotriene C 4 were evaluated. A small proportion (2.6%) of eosinophils spontaneously migrated through endothelial cell monolayers. Activation of endothelial cells by interleukin (IL)-4 or IL-1β slightly increased this migration (to 12.4%), which became much greater when a chemoattractant was placed in the lower chamber (84.3%). However, the chemotactic effect was downregulated by pretreating endothelial cells with interferon gamma (IFN-γ; 63.1%). At baseline, 5% of eosinophils expressed CD69; this increased to 30.7% in culture on untreated endothelial cells and to 50.9% on IL-1β-pretreated endothelial cells. This effect was mediated through intercellular adhesion molecule-1/CD11b interaction. Eosinophil migration through endothelial cells further increased CD69 expression to 63.9% and also increased CD35 expression from 83.3 to 91.3%. Upon stimulation, eosinophils that had migrated through endothelial cells produced more leukotriene C 4 than control cells (872.4 and 103.9 pg·mL −1 , respectively). Endothelial cell pretreatment with IL-4 or IL-1β further increased leukotriene C 4 release (1,789.1 and 2,895.1 pg·mL −1 , respectively), whereas pretreatment with IFN-γ decreased it (293.7 pg·mL −1 ). These data show that in vitro interactions with endothelial cells upregulate eosinophil membrane receptor expression and mediator release and that these effects are differently modulated by T-helper cell type 1 and 2 cytokines. These eosinophil modulations may play an important role in asthma pathogenesis.
COMPUTATIONAL NEUROIMAGING OF HUMAN VISUAL CORTEX
Authors: Brian A. Wandell
Journal: Annual Review of Neuroscience (1999)

Functional magnetic resonance imaging is a new neuroimaging method for probing the intact, alert, human brain. With this tool, brain activity that has been hidden can now be measured. Recent advances in measuring and understanding human neural responses underlying motion, color, and pattern perception are reviewed. In individual human brain, we can now identify the positions of several retinotopically organized visual areas; measure retinotopic organization within these areas; identify the location of a motion-sensitive region in individual brains; measure responses associated with contrast, color, and motion; and measure effects of attentional modulation on visually evoked responses. By framing experiments and analyses as questions about visual computation, these neuroimaging measurements can be coupled closely with those from other basic vision-science methods.
Keeping abdominal pain in the family
Authors: T. J. Cahill, A. Slater, S. P. L. Travis
Journal: Gut (2010)

A previously fit 30-year old software technician was admitted with a 2-week history of severe abdominal pain, associated with nausea and bloody diarrhoea. He had no medical or surgical history, was a non-smoker and took no medication or recreational drugs. His mother, brother and maternal grandmother had had deep vein thromboses or pulmonary emboli.

On examination he was afebrile, with central abdominal tenderness but no evidence of peritonism. His white cell count (16.1×109/litre) and C-reactive protein (CRP, 138 mg/litre) were elevated. Serum amylase and lactate were normal.

Chest and plain …
Human papillomavirus types 16 and 39 in a vulval carcinoma occurring in a woman with Hailey-Hailey disease
Authors: None OCHIAI, None HONDA, None MORISHIMA, None SATA, None SAKAMOTO, None SATOH
Journal: British Journal of Dermatology (1999)

A woman with Hailey–Hailey disease, suffering from carcinoma of the vulva, was examined by histology and for the presence of human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) and in situ hybridization. Our diagnosis by histological examination revealed the vulval carcinoma to be a squamous cell carcinoma (SCC), adjacent to lesions of Hailey–Hailey disease and severe dysplasia/carcinoma in situ [vulval intraepithelial neoplasia (VIN) III]. The PCR with consensus primers for the L1 region (L1-PCR) successfully amplified HPV DNA using total DNA extracted from formalin-fixed and paraffin-embedded tissue specimens. Restriction fragment length polymorphism analysis and sequencing of L1-PCR products revealed HPV types 16 and 39. HPV 16-specific primers for the E6 region identified HPV 16 DNA. In situ hybridization analysis with biotinylated HPV 16 and 39 DNA probes revealed the presence of the HPV 39 genome in the nuclei of the tumour cells in the SCC. These results indicate that HPV 16 and 39 are associated with lesions in vulval carcinoma. Regarding the patient's susceptibility to infection in the case of Hailey–Hailey disease, there is a possibility that HPV was inoculated into the lesions of Hailey–Hailey disease and induced those of VIN III and SCC.
Are eosinophilic pustular folliculitis of infancy and infantile acropustulosis the same entity?
Authors: J. VICENTE, A. ESPAÑA, M. IDOATE, M.E. IGLESIAS, E. QUINTANILLA
Journal: British Journal of Dermatology (1996)

An infant is described with an overlap picture of eosinophilic pustular folliculitis and infantile acropustulosis.
ACTIVATION OF LYSOSOMAL ENZYMES IN VIRUS-INFECTED CELLS AND ITS POSSIBLE RELATIONSHIP TO CYTOPATHIC EFFECTS
Authors: A. C. Allison, K. Sandelin
Journal: The Journal of Experimental Medicine (1963)

Activities of the enzymes ß-glucuronidase, acid phosphatase, acid DNAase, acid RNAase, and acid protease have been measured in the lysosomal and supernatant fractions of mouse liver cells and monkey kidney cells before and after infection with mouse hepatitis virus and vaccinia virus, respectively. In the infected cells there was easily measurable release of lysosomal enzymes into the supernatant fraction. Evidence was presented that this is not an artefact of homogenization and precedes cell degeneration demonstrable histologically. It is suggested that release of lysosomal enzymes may explain some of the biochemical changes found in infected cells and may contribute to the cytopathic effects of some viruses.
Restoration of Deficient Membrane Proteins in the Cardiomyopathic Hamster by In Vivo Cardiac Gene Transfer
Authors: Yasuhiro Ikeda, Yusu Gu, Yoshitaka Iwanaga, Masahiko Hoshijima, Sam S. Oh, Frank J. Giordano, Ju Chen, Vincenzo Nigro, Kirk L. Peterson, Kenneth R. Chien, John Ross
Journal: Circulation (2002)

Background — One of the most important problems in developing in vivo cardiac gene transfer has been low transfection efficiency. A novel in vivo technique was developed, tested in normal hamsters, and the feasibility of restoring a deficient structural protein (δ-sarcoglycan) in the cardiomyopathic (CM) hamster evaluated. Methods and Results — Adenoviral (AdV) vectors encoding either the lacZ gene or δ-sarcoglycan gene were constructed. Hypothermia was achieved in hamsters by external body cooling to a rectal temperature of 18 to 25°C. Through a small thoracotomy, the ascending aorta and the main pulmonary artery were occluded with snares, and cardioplegic solution containing histamine was injected into the aortic root; viral constructs were delivered 3 to 5 minutes later followed by release of the occluders and rewarming. Four days later, homogeneous β-galactosidase expression was detected throughout the ventricles of the normal hearts (average 77.3±9.0% [SEM] of left ventriclar myocytes). At 1 and 3 weeks after transfection, immunostaining showed extensive restoration of δ-sarcoglycan as well as α- and β-sarcoglycan proteins to the myocyte membranes, despite loss of β-galactosidase expression at 3 weeks. Also, at 3 weeks after gene transfer, there was significantly less progression of left ventricular dysfunction assessed as percent change in fractional shortening compared with controls. Conclusions — This study demonstrates the feasibility of high efficiency in vivo myocardial gene transfer and shows application in improving the level of a deficient cardiac structural protein and cardiac function in CM hamsters. The approach should be useful for assessing effects of expressing other genes that influence the structure or function of the normal and failing heart.
A controlled study of diet in patients with gout.
Authors: T Gibson, A V Rodgers, H A Simmonds, F Court-Brown, E Todd, V Meilton
Journal: Annals of the Rheumatic Diseases (1983)

To determine whether patients with gout have a diet which is distinctive in quality or quantity a careful dietary questionnaire was posed over 7 days to 61 men with gout and 52 control subjects. The average daily intake of most nutrients, including total purine nitrogen, was similar except that the patients with gout drank significantly more alcohol. Beer was the most popular beverage, and 25 (41%) of those with gout consumed more than 60 g alcohol daily (equivalent to 2 . 5 litres of beer). The heavy drinkers had a significantly higher intake of purine nitrogen, half of which was derived from beer. Though the effect of ingested purine on the blood uric acid is difficult to estimate, it probably was sufficient to have a clinical effect, augmenting the hyperuricaemic effect of alcohol itself.
Lansoprazole for the Prevention of Recurrences of Ulcer Complications from Long-Term Low-Dose Aspirin Use
Authors: Kam Chuen Lai, Shiu Kum Lam, Kent Man Chu, Benjamin C.Y. Wong, Wai Mo Hui, Wayne H.C. Hu, George K.K. Lau, Wai Man Wong, Man Fung Yuen, Annie O.O. Chan, Ching Lung Lai, John Wong
Journal: New England Journal of Medicine (2002)

The role of gastric acid suppression in preventing the recurrence of ulcer complications after the eradication of Helicobacter pylori infection in patients taking long-term low-dose aspirin is uncertain.We enrolled 123 patients who had ulcer complications after using low-dose aspirin continuously for more than one month and who had H. pylori infection. After the ulcers had healed and the H. pylori infection was eradicated, the patients were randomly assigned to treatment with 30 mg of lansoprazole daily or placebo, in addition to 100 mg of aspirin daily, for 12 months. The primary end point was the recurrence of ulcer complications.During a median follow-up of 12 months, 9 of the 61 patients in the placebo group (14.8 percent), as compared with 1 of the 62 patients in the lansoprazole group (1.6 percent), had a recurrence of ulcer complications (adjusted hazard ratio, 9.6; 95 percent confidence interval, 1.2 to 76.1). Of these 10 patients, 4 had evidence of a recurrence of H. pylori infection and 2 had taken nonsteroidal antiinflammatory drugs before the onset of complications. Patients in the lansoprazole group were significantly less likely to have a recurrence of ulcer complications than patients in the placebo group (P=0.008). There was no significant difference in mortality between the two groups.In patients who had ulcer complications related to the long-term use of low-dose aspirin, treatment with lansoprazole in addition to the eradication of H. pylori infection significantly reduced the rate of recurrence of ulcer complications.
Observations on the Extrinsic Neural Control of Cerebral Blood Flow in the Baboon
Authors: I. M. JAMES, R. A. Millar, M. J. PURVES
Journal: Circulation Research (1969)

Cerebral blood flow was measured using 133 xenon in forty-five baboons lightly anesthetized with pentobarbital. Blood flow varied between 62 and 82 ml/100g/min in gray matter and between 15 and 21 ml/100g/min in white matter. Hypercapnia and hypoxia caused a rise in blood flow and a fall in vascular resistance. Blood flow was independent of mean arterial blood pressure over the range 60 to 130 mm Hg. Section of the cervical sympathetic nerve enhanced the vascular response to CO 2 . Stimulation of the sympathetic nerve caused a reduction in blood flow in proportion to the initial blood flow. Similarly, after sympathectomy, blood flow was uniformly higher than control over the range of Pa o 2 tested (35 to 450 mm Hg). After sympathectomy, blood flow was little different from control at low blood pressure but was higher within the physiological range and blood flow then fell steadily as pressure was reduced. When the carotid, vagus, and aortic nerves were cut in the neck, the blood flow response to hypoxia and hypercapnia was reduced, and when the aortic or vagus nerves were stimulated centrally, blood flow increased independently of Pa CO 2 . Section of the seventh cranial nerve caused small and variable changes in blood flow, but if the vagus nerves had previously been sectioned, stimulation of the seventh cranial nerve caused an increase in blood flow in some of the tests. These results indicate that cerebral blood vessels are under reflex control. Possible receptors and pathways involved are discussed.
Impact of White-Coat Hypertension on Microvascular Complications in Type 2 Diabetes
Authors: Caroline K. Kramer, Cristiane B. Leitão, Luís H. Canani, Jorge L. Gross
Journal: Diabetes Care (2008)

The purpose of this study was to determine the impact of white-coat hypertension (WCH) on microvascular complications in type 2 diabetes.A cross-sectional study was conducted in normotensive patients and patients with WCH selected from a cohort of 319 type 2 diabetic patients. Normotension was defined by office blood pressure <140/90 mmHg and daytime blood pressure <135/85 mmHg on ambulatory blood pressure monitoring (ABPM). WCH was defined as office blood pressure >or=140/90 mmHg and daytime blood pressure <135/85 mmHg on ABPM. Subjects were evaluated for diabetic nephropathy (24-h urinary albumin excretion rate) and diabetic retinopathy (classified according to the Global Diabetic Retinopathy Group).Forty-six type 2 diabetic patients had WCH (14.4%; mean age 56.6 years; 45.3% men) and 117 had normotension (36.6%; mean age 55.8 years; 37.5% men). These groups did not differ in clinical and main laboratory characteristics. Systolic ABPM (24-h: 124.7 +/- 6.7 vs. 121.0 +/- 8.5 mmHg, P = 0.01 and daytime: 126.6 +/- 7.2 vs. 123.2 +/- 8.2 mmHg, P = 0.01) and blood pressure loads were higher in subjects with WCH than in the normotensive subjects. WCH was associated with an increased risk for macroalbuminuria (odds ratio 4.9 [95% CI 1.3-18.7], P = 0.01). On multivariate analysis models, WCH was associated with macroalbuminuria (2.0 [1.3-3.2], P = 0.02) and increased the risk for both nonproliferative and proliferative diabetic retinopathy (2.7 [1.2-6.6], P = 0.02 for any degree of diabetic retinopathy) after adjustments for confounding factors.Type 2 diabetic patients with WCH have an increased risk for diabetic retinopathy and diabetic nephropathy. Therefore, WCH should not be considered a harmless condition, and treatment should be considered.
The Importance of Doing Trials Right While Doing the Right Trials
Authors: David M. Dilts, Steven K. Cheng
Journal: Clinical Cancer Research (2011)

Abstract Effort is being expended in investigating efficiency measures (i.e., doing trials right) through achievement of accrual and endpoint goals for clinical trials. It is time to assess the impact of such trials on meeting the critical needs of cancer patients by establishing effectiveness measures (i.e., doing the right trials). Clin Cancer Res; 18(1); 3–5. ©2011 AACR.
Enriching for direct regulatory targets in perturbed gene-expression profiles
Authors: Susannah G Tringe, Andreas Wagner, Stephanie W Ruby
Journal: Genome biology (2004)

Here we build on a previously proposed algorithm to infer direct regulatory relationships using gene-expression profiles from cells in which individual genes are deleted or overexpressed. The updated algorithm can process networks containing feedback loops, incorporate positive and negative regulatory relationships during network reconstruction, and utilize data from double mutants to resolve ambiguous regulatory relationships. When applied to experimental data the reconstruction procedure preferentially retains direct transcription factor-target relationships.
A Comparison of the Malignancy Incidence Among Patients With Psoriatic Arthritis and Patients With Rheumatoid Arthritis in a Large US Cohort
Authors: Rachael L. Gross, Julie S. Schwartzman‐Morris, Michael Krathen, George Reed, Hong Chang, Katherine C. Saunders, Mark C. Fisher, Jeffrey D. Greenberg, Chaim Putterman, Philip J. Mease, Alice B. Gottlieb, Joel M. Kremer, Anna Broder
Journal: Arthritis & Rheumatology (2014)

To compare the incidence rates of malignancy among patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) registry.We analyzed 2,970 patients with PsA (7,133 patient-years of followup) and 19,260 patients with RA (53,864 patient-years of followup). Using a standardized adjudication process, we identified 40 confirmed malignancies in the patients with PsA and 307 confirmed malignancies in those with RA. Incidence rates were calculated per 100 patient-years. Incidence rate ratios were estimated, with adjustment for age, sex, disease duration, body mass index, disease activity, year of enrollment, and medication use.The overall malignancy incidence per 100 patient-years was similar between patients with PsA and patients with RA (0.56 [95% confidence interval (95% CI) 0.40-0.76] and 0.56 [95% CI 0.50-0.63], respectively). Nonmelanoma skin cancer was the most common type of cancer in the overall cohort, with an incidence rate of 0.21 (95% CI 0.12-0.35) in PsA, and 0.20 (95% CI 0.17-0.24) in RA, with a calculated incidence rate ratio of 1.05 (95% CI 0.61-1.80; P = 0.85). Lymphoma rates were similar in PsA and RA (0.04 [95% CI 0.01-0.12] and 0.04 [95% CI 0.02-0.06], respectively; incidence rate ratio 1.00 [95% CI 0.17-3.11]; P = 0.67). The adjusted incidence rate ratio of malignancy in PsA versus RA was 1.17 (95% CI 0.82-1.69; P = 0.37).The incidence rates across malignancy subtypes were similar in the PsA and RA cohorts from a US registry.
Economics and the New Generation of Targeted Therapies for Non-Small Cell Lung Cancer
Authors: S. D. Ramsey
Journal: JNCI Journal of the National Cancer Institute (2010)

Lung cancer is probably the most substantial cancer problem faced by public and private health-care systems in the developed world, in terms of its human impact on lives lost and morbidity burden and in terms of its budget impact on those health-care systems. New treatments for lung cancer are thus an opportunity and a threat to every system that simultaneously seeks to improve the health of its members or citizens and to work within ever-tightening budget constraints. Most health-care payers outside the United States manage this tension between the needs for fiscal responsibility while improving health by using cost-effectiveness analyses to guide coverage and reimbursement for new treatments. Erlotinib, a tyrosine kinase inhibitor, is an excellent example of the many challenges posed to health systems by modern targeted therapies in cancer. First, erlotinib has unequivocally been shown to be effective—albeit modestly so—for progression after platinum-based first-line chemotherapy for patients with non– small cell lung cancer. Because the tumors of almost all of these patients will eventually progress, erlotinib could in theory be seen as an extension of the general pharmacological management of lung cancer, with incremental impact on the overall budget for managing these patients. Should systems then expect (and support) erlotinib as part of the overall management? Second, emerging pharmacogenomic information indicates that we might be able to
Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo: tau phosphorylation in APP mice by diabetes
Authors: Naoyuki Sato
Journal: Molecular Neurodegeneration (2013)

Background Epidemiological studies suggest that diabetes mellitus increases the risk of onset of Alzheimer disease (AD). However, the underlying mechanisms have not been fully understood. Retrospective studies indicate that diabetes does not increase senile plaques. On the other hand, a Japanese cohort, Hisayama study suggested that insulin resistance in midlife increased the risk of development of senile plaques. Therefore, the aim of this study is to understand the mechanisms by which diabetes increase the risk of AD by dividing them into two phases; 1) before and 2) after the development of senile plaques.
Effects of Acute Mental Stress and Exercise on T-Wave Alternans in Patients With Implantable Cardioverter Defibrillators and Controls
Authors: Willem J. Kop, David S. Krantz, Bruce D. Nearing, John S. Gottdiener, John F. Quigley, Mark O’Callahan, Albert A. DelNegro, Ted D. Friehling, Pamela Karasik, Sonia Suchday, Joseph Levine, Richard L. Verrier
Journal: Circulation (2004)

Background— Malignant cardiac arrhythmias can be triggered by exercise and by mental stress in vulnerable patients. Exercise-induced T-wave alternans (TWA) is an established marker of cardiac electrical instability. However, the effects of acute mental stress on TWA have not been investigated as a vulnerability marker in humans. Methods and Results— TWA responses to mental stress (anger recall and mental arithmetic) and bicycle ergometry were evaluated in patients with implantable cardioverter defibrillators (ICDs) and documented coronary artery disease (n=23, age 62.1±12.3 years) and controls (n=17, age 54.2±12.1 years). TWA was assessed from digitized ECGs by modified moving average analysis. Dual-isotope single photon emission computed tomography was used to assess myocardial ischemia. TWA increased during mental stress and exercise ( P values &lt;0.001), and TWA responses were higher in ICD patients than in controls (arithmetic Δ=8.9±1.4 versus 4.3±2.2 μV, P =0.043; exercise Δ=21.4±2.8 versus 13.8±3.2 μV, P =0.038). TWA increases with mental stress occurred at substantially lower heart rates (anger recall Δ=9.7±7.7 bpm, arithmetic Δ=14.3±13.3 bpm) versus exercise (Δ=53.7±22.7 bpm; P values &lt;0.001). After adjustment for heart rate increases, mental stress and exercise provoked increased TWA in ICD patients ( P values &lt;0.05), but not in controls ( P values &gt;0.2). Ejection fraction and stress-induced myocardial ischemia were not associated with TWA. Conclusions— Mental stress can induce cardiac electrical instability, as assessed via TWA, among patients with arrhythmic vulnerability and occurs at lower heart rates than with exercise. Pathophysiological mechanisms of mental stress–induced arrhythmias may therefore involve central and autonomic nervous system pathways that differ from exercise-induced arrhythmias.