tbuckley/cabot-search huggingface dataset:
Modulation of hepatic sinusoidal endothelial cell function by Kupffer cells: An example of intercellular communication in the liver
Authors: Ion V. Deaciuc, Gregory J. Bagby, Michael R. Niesman, Nebojsa Skrepnik, John J. Spitzer
Journal: Hepatology (1994)

We tested the hypothesis that Kupffer cells modulate sinusoidal endothelial cell function in the liver. Rats were treated with Kupffer cell-depleting agents (gadolinium chloride and liposome-encapsulated dichloromethylene diphosphonate) or with inhibitors of phospholipase A2 or leukotriene A4 synthase (dexamethasone and diethylcarbamazine, respectively). Hyaluronan uptake by the isolated, perfused liver was measured as an index of the functional state of the sinusoidal endothelial cell. Plasma hyaluronan concentration was also determined. Three hours after Escherichia coli lipopolysaccharide administration (100 micrograms/100 gm body wt, intravenously) plasma hyaluronan levels were significantly increased (280% to 320%), whereas hepatic hyaluronan uptake was markedly decreased (approximately 76%). Pretreatment with gadolinium chloride (0.5 mg/100 gm body wt, intravenously, 21 hr before saline solution or lipopolysaccharide administration), liposome-encapsulated dichloromethylene diphosphonate (40 mumol/100 gm body wt, intravenously, 44 hr before saline solution or lipopolysaccharide injection), dexamethasone (40 micrograms/100 gm body wt, intravenously, 1 hr before saline solution or lipopolysaccharide administration) or diethylcarbamazine (repeated doses, 10 mg/100 gm body wt, intravenously, 1 hr before saline solution or lipopolysaccharide injection) counteracted the lipopolysaccharide inhibitory effect on hepatic hyaluronan uptake. With the exception of gadolinium chloride, all other agents also prevented the lipopolysaccharide-induced increase in plasma hyaluronan concentration. Gadolinium chloride only attenuated the lipopolysaccharide effect on plasma hyaluronan level. Taken together with earlier results from our laboratory, these data indicate that: (a) Kupffer cell activation by lipopolysaccharide results in suppression of hyaluronan uptake by sinusoidal endothelial cells and (b) such modulation of endothelial cell function is likely mediated by products of the lipoxygenase pathway of arachidonate metabolism.
Duodenal mass in a patient with weight loss and liver dysfunction
Authors: T. Tsujino, Y. Ito, H. Yoshida, S. Ikushima, T. Takemura, R. Nakata, K. Koike
Journal: Gut (2010)

A 59-year-old Japanese man presented to our hospital with loss of appetite and 7 kg decrease in weight over 6 months. His medical history was unremarkable, except for hearing difficulty. He took medication for hypertension. His vital signs and physical examination were normal. Laboratory data at presentation were as follows: total bilirubin 0.4 mg/dl (reference 0.2–1.0); alanine aminotransferase 58 IU/l (reference 10–40); aspartate aminotransferase 68 IU/l (reference 5–40); alkaline phosphatase 697 IU/l (reference 104–338); gamma-glutamyl transpeptidase 178 IU/l (reference 0–79); white blood cells 4300/microlitre (reference 3700–9300); haemoglobin 12.1 g/dl (reference 13.0–16.5); blood urea nitrogen 38 mg/dl (reference 8–20); and creatinine 3.50 mg/dl (reference 0.50–1.20). Tests for hepatitis B and C were negative.

Abdominal ultrasonography demonstrated slightly increased echogenicity of the liver …
Adaptive Evolution in the Photosensory Domain of Phytochrome A in Early Angiosperms
Authors: S. Mathews
Journal: Molecular Biology and Evolution (2003)

Flowering plant diversity now far exceeds the combined diversity of all other plant groups. Recently identified extant remnants of the earliest-diverging lines suggest that the first angiosperms may have lived in shady, disturbed, and moist understory habitats, and that the aquatic habit also arose early. This would have required the capacity to begin life in dimly lit environments. If so, evolution in light-sensing mechanisms may have been crucial to their success. The photoreceptor phytochrome A is unique among angiosperm phytochromes in its capacity to serve a transient role under conditions where an extremely high sensitivity is required. We present evidence of altered functional constraints between phytochrome A (PHYA) and its paralog, PHYC. Tests for selection suggest that an elevation in nonsynonymous rates resulted from an episode of selection along the branch leading to all angiosperm PHYA sequences. Most nucleotide sites (95%) are selectively constrained, and the ratio of nonsynonymous to synonymous substitutions on branches within the PHYA clade does not differ from the ratio on the branches in the PHYC clade. Thus, positive selection at a handful of sites, rather than relaxation of selective constraints, apparently has played a major role in the evolution of the photosensory domain of phytochrome A. The episode of selection occurred very early in the history of flowering plants, suggesting that innovation in phyA may have given the first angiosperms some adaptive advantage.
Fatty Acid Binding Protein 6 Is Overexpressed in Colorectal Cancer
Authors: Takahiro Ohmachi, Hiroshi Inoue, Koshi Mimori, Fumiaki Tanaka, Atsushi Sasaki, Tatsuo Kanda, Hiroshi Fujii, Katsuhiko Yanaga, Masaki Mori
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer. Experimental Design: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles. Results: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P &amp;lt; 0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P &amp;lt; 0.01), more often in the left colon (P &amp;lt; 0.05), and had shallower invasion into the bowel wall (P &amp;lt; 0.05) compared with those with low expression. There was no significant difference between high- and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P &amp;lt; 0.05), more dominant proliferation (P &amp;lt; 0.001), and less apoptosis than mock cells. Conclusions: The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.
White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism
Authors: Jed T. Elison, Sarah J. Paterson, Jason J. Wolff, J. Steven Reznick, Noah J. Sasson, Hongbin Gu, Kelly N. Botteron, Stephen R. Dager, Annette M. Estes, Alan C. Evans, Guido Gerig, Heather C. Hazlett, Robert T. Schultz, Martin Styner, Lonnie Zwaigenbaum, Joseph Piven
Journal: American Journal of Psychiatry (2013)

Objective-The authors sought to determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors.Method-Data were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants.All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months.Diffusionweighted imaging data were acquired for 84 of the infants at 7 months.Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum.Results-Visual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants.Visual orienting latencies were uniquely associated with the microstructural organization of the
Toward a Systems Approach to Enteric Pathogen Transmission: From Individual Independence to Community Interdependence
Authors: Joseph N.S. Eisenberg, James Trostle, Reed J.D. Sorensen, Katherine F. Shields
Journal: Annual Review of Public Health (2012)

Diarrheal disease is still a major cause of mortality and morbidity worldwide; thus a large body of research has been produced describing its risks. We review more than four decades of literature on diarrheal disease epidemiology. These studies detail a progression in the conceptual understanding of transmission of enteric pathogens and demonstrate that diarrheal disease is caused by many interdependent pathways. However, arguments by diarrheal disease researchers in favor of attending to interaction and interdependencies have only recently yielded more formal systems-level approaches. Therefore, interdependence has not yet been highlighted in significant new research initiatives or policy decisions. We argue for a systems-level framework that will contextualize transmission and inform prevention and control efforts so that they can integrate transmission pathways. These systems approaches should be employed to account for community effects (i.e., interactions among individuals and/or households).
Assessment of variability of exercise tolerance limited by breathlessness.
Authors: E T Peel, C A Soutar, A Seaton
Journal: Thorax (1988)

A sequence of questions was designed to quantify the within subject variation of exercise tolerance limited by breathlessness, to serve as a guide to variation in airflow limitation for epidemiological purposes. The questions seek answers about breathlessness in relation to various levels of attempted activity when the subjects are at their best and at their worst. The difference between exercise tolerance at best and exercise tolerance at worst (variation in exercise tolerance) was expressed on a scale ranging from 0 (no variation) to 6 (greatest variation). The effectiveness of these questions has been assessed in 68 patients with airflow limitation attending a chest clinic, by comparing the results with variation in peak expiratory flow rate (PEF). Variation in PEF was expressed as the standard deviation of the first 24 PEF recordings from each patient (equivalent to four days' recordings). There was a highly significant relation between the measure of variation in exercise tolerance obtained from the questionnaire and PEF variation, though each point on the scale of variation in exercise tolerance covered a wide range of variation in PEF. The questions give some guide to the variation in airflow limitation and in combination with other questions may be helpful in epidemiological studies.
Deciphering the transcriptional network of the dendritic cell lineage
Authors: Jennifer C Miller, Brian D Brown, Tal Shay, Emmanuel L Gautier, Vladimir Jojic, Ariella Cohain, Gaurav Pandey, Marylene Leboeuf, Kutlu G Elpek, Julie Helft, Daigo Hashimoto, Andrew Chow, Jeremy Price, Melanie Greter, Milena Bogunovic, Angelique Bellemare-Pelletier, Paul S Frenette, Gwendalyn J Randolph, Shannon J Turley, Miriam Merad
Journal: Nature Immunology (2012)
What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease
Authors: F M McQueen, N Benton, J Crabbe, E Robinson, S Yeoman, L McLean, N Stewart
Journal: Annals of the Rheumatic Diseases (2001)

To investigate the progression of erosions at sites within the carpus, in patients with early rheumatoid arthritis (RA), using magnetic resonance imaging (MRI) and plain radiology over a two year period.Gadolinium enhanced MRI scans of the dominant wrist were performed in 42 patients with RA at baseline (within six months of symptom onset) and one year. Plain wrist radiographs (x rays) and clinical data were obtained at baseline, one year, and two years. Erosions were scored by two musculoskeletal radiologists on MRI and x ray at 15 sites in the wrist. A patient centred analysis was used to evaluate the prognostic value of a baseline MRI scan. A lesion centred analysis was used to track the progression of individual erosions over two years.The baseline MRI erosion score was predictive of x ray erosion score at two years (p=0.004). Patients with a "total MRI score" (erosion, bone oedema, synovitis, and tendonitis) > or =13 at baseline were significantly more likely to develop erosions on x ray at two years (odds ratio 13.4, 95% CI 2.65 to 60.5, p=0.002). Baseline wrist MRI has a sensitivity of 80%, a specificity of 76%, a positive predictive value of 67%, and a high negative predictive value of 86% for the prediction of wrist x ray erosions at two years. A lesion centred analysis, which included erosions scored by one or both radiologists, showed that 84% of baseline MRI erosions were still present at one year. When a more stringent analysis was used which required complete concordance between radiologists, all baseline lesions persisted at one year. The number of MRI erosion sites in each patient increased from 2.1 (SD 2.7) to 5.0 (4.6) (p<0.0001) over the first year of disease. When MRI erosion sites were tracked, 21% and 26% were observed on x ray, one and two years later. A high baseline MRI synovitis score, Ritchie score, and erythrocyte sedimentation rate were predictive of progression of MRI erosions to x ray erosions over one year (p=0.005, 0.01, and 0.03 respectively), but there was no association with the shared epitope. Progression of MRI erosions to x ray erosions was not seen in those with transient polyarthritis.MRI scans of the wrist, taken when patients first present with RA, can predict radiographic erosions at two years. MRI may have a role in the assessment of disease prognosis and selection of patients for more or less aggressive treatment. However, only one in four MRI erosions progresses to an x ray erosion over one year, possibly owing to healing, observer error, or technical limitations of radiography at the carpus. Progression of MRI erosions to x ray erosions is greatest in those with high baseline disease activity.
In-Hospital and 1-Year Mortality in Patients Undergoing Early Surgery for Prosthetic Valve Endocarditis
Authors: Tahaniyat Lalani
Journal: JAMA Internal Medicine (2013)

There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE).To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias.Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum.Valve replacement during index hospitalization (early surgery) vs medical therapy.In-hospital and 1-year mortality.Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity.Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.
Normalization of Postinfarct Biomechanics Using a Novel Tissue-Engineered Angiogenic Construct
Authors: Pavan Atluri, Alen Trubelja, Alexander S. Fairman, Philip Hsiao, John W. MacArthur, Jeffrey E. Cohen, Yasuhiro Shudo, John R. Frederick, Y. Joseph Woo
Journal: Circulation (2013)

Background— Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics. Methods and Results— EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5×10 6 cells/cm 2 on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell–derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC–matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P =0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P =0.1; versus infarct=304 kPa, P =0.01). Conclusions— We demonstrate restoration and normalization of post–myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.
Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease
Authors: W Dieterich
Journal: Gut (2005)

Intestinal inflammation in coeliac disease is driven by the gluten fraction of wheat proteins. Deamidation or cross linking of gluten peptides by tissue transglutaminase (tTG), the coeliac disease autoantigen, creates potent T cell stimulatory peptides. Therefore, our aim was to identify the reaction patterns of gluten peptides, intestinal extracellular matrix proteins, and tTG.tTG activity was analysed by incorporation of monodansyl cadaverine into gliadins. Fluorescence labelled tTG reactive short gliadin peptides were used to demonstrate their deamidation and explore their cross linking patterns with tTG itself or extracellular matrix proteins. Patient sera and controls were checked for autoantibodies to matrix proteins.Gliadins alpha1-alpha11, gamma1-gamma6, omega1-omega3, and omega5 were substrates for tTG. tTG catalysed the cross linking of gliadin peptides with interstitial collagen types I, III, and VI. Coeliac patients showed increased antibody titres against the collagens I, III, V, and VI.tTG formed high molecular weight complexes with all tested gliadins. As all tested gliadins were substrates for tTG, the tTG catalysed modifications were not restricted to single gliadin types and epitopes. Furthermore, haptenisation and long term immobilisation of gliadin peptides by tTG catalysed binding to abundant extracellular matrix proteins could be instrumental in the perpetuation of intestinal inflammation and some associated autoimmune diseases in coeliac disease.
Higher sugar intake linked to raised risk of cardiovascular mortality, study finds
Authors: M. McCarthy
Journal: BMJ (2014)

Higher consumption of added sugar is associated with an increased risk of cardiovascular mortality, a new US study has shown.1

The researchers evaluated data from the National Health and Nutrition Examination Survey, a series of cross sectional surveys that include physical examinations and interview of participants concerning 24 hour dietary recall and a related linked mortality cohort of a nationally representative sample of US adults.

Quanhe Yang of the Division for Heart Disease and Stroke Prevention at the Centers for Disease Control and Prevention in Atlanta, Georgia, was the lead author of the paper, which was published on 3 February by JAMA Internal Medicine .

The researchers found that added sugar—such as sugar found in baked goods, processed and prepared foods, and sweetened beverages—accounted for more than 10% of the energy intake of …
A Placebo-controlled Trial of a HEPA Air Cleaner in the Treatment of Cat Allergy
Authors: ROBERT A. WOOD, ELIZABETH F. JOHNSON, MARK L. VAN NATTA, PEI HUA CHEN, PEYTON A. EGGLESTON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To evaluate the effect of a room high-efficiency particulate air (HEPA) cleaner on cat-induced asthma and rhinitis, 35 cat-allergic subjects who were living with one or more cats were studied in a double-blind, placebo controlled trial. After a 1 mo baseline period, subjects' bedrooms were equipped with an active or placebo air cleaner for the following 3 mo. Evaluations included monthly measurement of cat-allergen levels, daily morning, afternoon, and nighttime nasal- and chest-symptom scores, twice-daily measurement of peak-flow rates, daily medication scores, monthly spirometry, and methacholine (MCh) challenge testing before and after the study. Airborne allergen levels were reduced in the active-filter group as compared with the placebo group (p = 0.045). However, no differences were detected in settled-dust allergen levels (p = 0.485), morning, afternoon, or nighttime nasal-symptom scores (p = 0.769, 0.534, and 0.138), chest-symptom scores (p = 0.388, 0.179, and 0.215), sleep disturbance (p = 0.101), morning or afternoon peak-flow rates (p = 0.424 and 0.679), or rescue medication use (nasal, p = 0.164, chest, p = 0.650), respectively. Although the combination of a HEPA room air cleaner, mattress and pillow covers, and cat exclusion from the bedroom did reduce airborne cat-allergen levels, no effect on disease activity was detected for any parameter studied.