tbuckley/cabot-search huggingface dataset:
Establishment of Conditionally Immortalized Mouse Glomerular Parietal Epithelial Cells in Culture
Authors: Takamoto Ohse, Jeffrey W. Pippin, Michael R. Vaughan, Paul T. Brinkkoetter, Ronald D. Krofft, Stuart J. Shankland
Journal: Journal of the American Society of Nephrology (2008)

In the skin, there exist at least two populations of dendritic cells (DCs), epidermal Langerhans cells (LCs) and dermal DCs. It has been reported that cutaneous DCs mediate the pathogenesis of atopic dermatitis (AD), but it remain unknown which subset is directly involved. Using mice with Langerin-diphtheria toxin receptor, we found that LC depletion showed much milder clinical manifestations together with lower serum IgE levels in a topical OVA application-induced AD-like mouse model. In addition, LC depletion impaired OVA-specific T cell proliferation and IL-4 production in the draining lymph nodes. Recent work has identified TSLP as promoting Th2-dominant inflammations. Since TSLP is expressed in the epidermis, we hypothesize that TSLP secreted by keratinocytes acts on epidermal LCs to prime naïve T cells into Th2 cells. To this end, we used TSLP receptor-deficient mice and newly generated LC-specific TSLP receptor-deficient mice by bone marrow reconstitution of wild-type mice into irradiated TSLP-receptor deficient mice by taking advantage of radio-resistance of LCs. We induced AD-like skin conditions to these mice by sensitization with OVA percutaneously. We found that LC-specific TSLP receptor-deficient mice showed much milder clinical and histological findings together with lower IL-4 and IgE levels. Taken together, these results suggest that epidermal LCs play a critical role in the development of AD via TSLP-TSLP receptor signaling.
Estimating Divergence Dates and Substitution Rates in the Drosophila Phylogeny
Authors: Darren J. Obbard, John Maclennan, Kang-Wook Kim, Andrew Rambaut, Patrick M. O’Grady, Francis M. Jiggins
Journal: Molecular Biology and Evolution (2012)

An absolute timescale for evolution is essential if we are to associate evolutionary phenomena, such as adaptation or speciation, with potential causes, such as geological activity or climatic change. Timescales in most phylogenetic studies use geologically dated fossils or phylogeographic events as calibration points, but more recently, it has also become possible to use experimentally derived estimates of the mutation rate as a proxy for substitution rates. The large radiation of drosophilid taxa endemic to the Hawaiian islands has provided multiple calibration points for the Drosophila phylogeny, thanks to the "conveyor belt" process by which this archipelago forms and is colonized by species. However, published date estimates for key nodes in the Drosophila phylogeny vary widely, and many are based on simplistic models of colonization and coalescence or on estimates of island age that are not current. In this study, we use new sequence data from seven species of Hawaiian Drosophila to examine a range of explicit coalescent models and estimate substitution rates. We use these rates, along with a published experimentally determined mutation rate, to date key events in drosophilid evolution. Surprisingly, our estimate for the date for the most recent common ancestor of the genus Drosophila based on mutation rate (25–40 Ma) is closer to being compatible with independent fossil-derived dates (20–50 Ma) than are most of the Hawaiian-calibration models and also has smaller uncertainty. We find that Hawaiian-calibrated dates are extremely sensitive to model choice and give rise to point estimates that range between 26 and 192 Ma, depending on the details of the model. Potential problems with the Hawaiian calibration may arise from systematic variation in the molecular clock due to the long generation time of Hawaiian Drosophila compared with other Drosophila and/or uncertainty in linking island formation dates with colonization dates. As either source of error will bias estimates of divergence time, we suggest mutation rate estimates be used until better models are available.
Regulation of CD1d expression and function by a herpesvirus infection
Authors: David Jesse Sanchez, Jenny E. Gumperz, Don Ganem
Journal: Journal of Clinical Investigation (2005)

Little is known about the role of CD1d-restricted T cells in antiviral immune responses. Here we show that the lytic replication cycle of the Kaposi sarcoma–associated herpesvirus (KSHV) promotes downregulation of cell-surface CD1d. This is caused by expression of the 2 modulator of immune recognition (MIR) proteins of the virus, each of which promotes the loss of surface CD1d expression following transfection into uninfected cells. Inhibition of CD1d surface expression is due to ubiquitination of the CD1d α-chain on a unique lysine residue in its cytoplasmic tail, which triggers endocytosis. Unlike MIR-mediated MHC class I downregulation, however, CD1d downregulation does not appear to include accelerated lysosomal degradation. MIR2-induced downregulation of CD1d results in reduced activation of CD1d-restricted T cells in vitro. KSHV modulation of CD1d expression represents a strategy for viral evasion of innate host immune responses and implicates CD1d-restricted T cells as regulators of this viral infection.
Renal responses of the fetal lamb to fetal or maternal volume expansion.
Authors: J K Hurley, S E Kirkpatrick, P T Pitlick, W F Friedman, S A Mendoza
Journal: Circulation Research (1977)

Fetal and maternal glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, sodium excretion, and fractional sodium reabsorption were measured in a chronically instrumented sheep preparation. Fetal GFR was essentially stable between 110 and 135 days of gestation (term = 147 days). There was a significant increase in GFR after 135 days. After the infusion of 50 ml of normal saline over a 30-minute period, fetal GFR and sodium excretion increased significantly. Fractional sodium reabsorption was significantly decreased. Thus, the fetus is capable of responding to volume expansion with saline with an increase in GFR and a decrease in fractional sodium reabsorption. After the infusion of 1000 ml of normal saline into the ewe in 1 hour, maternal GFR and RPF rose significantly. Sodium excretion rose 6-fold and fractional sodium reabsorption fell significantly. After the infusion of saline into the ewe, there was no change in fetal GFR, RPF, sodium excretion, urine volume, or fractional sodium reabsorption. Since there were no changes in fetal renal function after maternal volume expansion with saline there was no evidence for the transplacental passage of a natriuretic factor from ewe to fetus.
Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism
Authors: C. K. Wong, J. Cao, Y. B. Yin, C. W. K. Lam
Journal: European Respiratory Journal (2009)

Basophils are the accessory cell type for T-helper (Th)2 induction and initiators in immunoglobulin E-mediated chronic allergic inflammation. Basophils and Th17 cells accumulate at the inflammatory sites, such as the airways of allergic asthmatic patients. We investigated the activation of interleukin (IL)-17A on the primary human basophils/KU812 basophilic cells and primary human bronchial epithelial cells/BEAS-2B bronchial epithelial cells. Cytokines, chemokines, adhesion molecules and intracellular signalling molecules were assayed by ELISA or flow cytometry. Co-culture of bronchial epithelial cells and basophils could significantly induce the release of IL-6, an epithelial inflammatory cytokine, and CCL2, a chemokine for basophils, esosinophils and monocytes. Such induction was synergistically enhanced by IL-17A, and direct interaction between these two cells was necessary for IL-17A-induced IL-6 and CCL2 release. Surface expression of intercellular adhesion molecule-1 on bronchial epithelial cells was also upregulated upon their interaction. The interaction of basophils and bronchial epithelial cells under IL-17A stimulation was differentially regulated by extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38 mitogen-activated protein kinase and nuclear factor-κB pathways. These findings suggest a novel immunopathological role of Th17 cells and basophils in allergic asthma through the activation of granulocyte-mediated inflammation initiated by the direct interaction between basophils and bronchial epithelial cells.
The nonerythropoietic component of early bilirubin
Authors: M. Levitt, B. A. Schacter, A. Zipursky, L. G. Israels
Journal: Journal of Clinical Investigation (1968)

The early labeled bilirubin consists of two primary components. The more rapidly synthesized of the two is independent of erythropoiesis (nonerythropoietic), whereas the second fraction is related to red cell production (erythyropoietic). The present studies concern the origin of the nonerythropoietic component. The nonerythropoietic, early labeled bilirubin was studied in bile fistula rats with (delta ALA)-4-(14)C delta aminolevulinic acid and glycine-2-(14)C as precursors. That nephrectomy did not reduce the size of this component despite the large and rapidly turning over pool of renal heme suggests that this pool may be of minor importance in its production. Intoxication with lead to a level that reduced hepatic heme synthesis was associated with a decrease in early bilirubin formation. The synthesis of this bilirubin was assessed in animals with phenobarbital-induced heme protein and cycloheximide-suppressed protein synthesis. Rats pretreated with phenobarbital at a dose level of 60 mg/kg with induction of cytochrome P-450 synthesis showed a minor increase in early labeling when glycine-2-(14)C but not when delta ALA-4-(14)C was used as precursor. Rats given cycloheximide at a dose level that markedly reduced hepatic protein and cytochrome P-450 synthesis but allowed heme synthesis to continue at 60% of its pretreatment level synthesized normal or increased amounts of early bilirubin from delta ALA-4-(14)C. Allylisopropylacetamide intoxication caused little change in early bilirubin formation, whereas aminotriazole given at a time after maximal hepatic heme labeling produced a small but significant increase in the appearance of labeled bilirubin. These findings indicate that early bilirubin production is little influenced by increased hepatic porphyrin synthesis or by changes in the rapidly turning over heme protein P-450. A minimal increase attends catalase inactivation by aminotriazole. Normal or increased synthesis takes place in the presence of suppression of protein synthesis. This finding suggests that the nonerythropoietic early bilirubin may itself consist of two subcomponents. The first of these may arise from free tissue heme or its precursors, and the second may derive from the turnover of the heme proteins. The first subcomponent may serve as a regulatory mechanism for the removal of heme synthesized in excess of its protein acceptor. A composite scheme is proposed for the origin of the total early bilirubin from heme compartments in tissue and marrow.
Living Near a Main Road and the Risk of Wheezing Illness in Children
Authors: ANDREA J. VENN, SARAH A. LEWIS, MARIE COOPER, RICHARD HUBBARD, JOHN BRITTON
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The effect of road vehicle traffic pollution on asthma is still not clearly understood. However, any effect is likely to be most marked among those who live within 150 m of a main road, because this is the distance within which concentrations of primary vehicle traffic pollutants are raised above ambient background levels. We have investigated the relation between proximity of the family home to the nearest main road, estimated objectively using geographical information system software, and the risk of wheeze in the past year in a case-control sample of 6,147 primary schoolchildren (age 4 to 11 yr) and a random cross-sectional sample of 3,709 secondary schoolchildren (age 11 to 16 yr) in Nottingham, United Kingdom. Among children living within 150 m of a main road, the risk of wheeze increased with increasing proximity by an odds ratio (OR) of 1.08 (95% confidence interval [CI] 1.00 to 1.16) per 30-m increment in primary schoolchildren, and 1.16 (1.02 to 1.32) in secondary schoolchildren. Most of the increased risk was localized to within 90 m of the roadside. Among primary schoolchildren, effects were stronger in girls than boys (pinteraction = 0.02). Living within approximately 90 m of a main road is associated with a proximity-related increase in the risk of wheezing illness in children.
Expression of a Fibroblast Growth Factor–Binding Protein during the Development of Adenocarcinoma of the Pancreas and Colon
Authors: Elena Tassi, Ralf T. Henke, Emma T. Bowden, Matthew R. Swift, David P. Kodack, Angera H. Kuo, Anirban Maitra, Anton Wellstein
Journal: Cancer Research (2006)

Abstract The activity of growth factors is crucial for tumor progression. We previously characterized a secreted fibroblast growth factor–binding protein (FGF-BP1) as a chaperone molecule, which enhances the biological functions of FGFs by releasing FGFs from the extracellular matrix. Here, we characterize the frequency and pattern of FGF-BP1 expression during the malignant progression of pancreas and colorectal carcinoma. For this, we generated monoclonal antibodies that detect FGF-BP1 protein in formalin-fixed, paraffin-embedded tissues and applied in situ hybridization to detect FGF-BP1 mRNA in adjacent tissue sections. FGF-BP1 protein and mRNA were found up-regulated (&amp;gt;70% positive) in parallel (r = 0.70, P &amp;lt; 0.0001) in colon adenoma (n = 9) as well as primary (n = 46) and metastatic (n = 71) colorectal cancers relative to normal colon epithelia (all P &amp;lt; 0.0001, versus normal). Similarly, pancreatitis (n = 17), pancreatic intraepithelial neoplasia (n = 80), and pancreatic adenocarcinoma (n = 67) showed a significant up-regulation of FGF-BP1 compared with normal pancreas (n = 42; all P &amp;lt; 0.0001, relative to normal). Furthermore, the biological activity of FGF-BP1 is neutralized by one of the antibodies, suggesting the potential for antibody-based therapeutic targeting. We propose that the up-regulation of the secreted FGF-BP1 protein during initiation of pancreas and colon neoplasia could make this protein a possible serum marker indicating the presence of high-risk premalignant lesions. (Cancer Res 2006; 66(2): 1191-8)
Ventricular coupling in constrictive pericarditis.
Authors: W P Santamore, R Bartlett, S J Van Buren, M K Dowd, M A Kutcher
Journal: Circulation (1986)

Because of the close anatomic association, the volume or pressure in one ventricle can directly influence the volume and pressure in the other ventricle. Disease states that reduce pericardial compliance should accentuate this coupling between the ventricles. We examined this hypothesis in six dogs. Constrictive pericarditis was induced by injecting an irritant mixture into the pericardial cavity. Three to 4 weeks after this injection, the hearts were removed and placed in cool cardioplegic solution. Balloons were inserted into each ventricle and the pressure and volume changes caused by increasing the contralateral ventricular volume were measured. Compared with that in a control group of four dogs, the coupling between the ventricles was significantly augmented in the group with constrictive pericarditis. All the measured changes in ventricular pressure or volume caused by increasing contralateral ventricular pressure or volume were significantly greater (p less than .05) in the group with constrictive pericarditis. The results of these experiments show increased coupling between the ventricles with constrictive pericarditis, which helps to explain some of the signs and symptoms of constrictive pericarditis.
Xenoestrogen Action in Prostate Cancer: Pleiotropic Effects Dependent on Androgen Receptor Status
Authors: Yelena B. Wetherill, Nicola L. Fisher, Ann Staubach, Mark Danielsen, Ralph W. de Vere White, Karen E. Knudsen
Journal: Cancer Research (2005)

Androgen is critical for prostate development, growth, and survival. Therapies for advanced prostate cancer aim to block androgen receptor (AR) action. However, recurrent tumors ultimately arise, which harbor restored AR activity. One mechanism of such reactivation occurs through AR mutations, rendering the receptor responsive to noncanonical ligands. We have shown previously that a known xenoestrogen, bisphenol A (BPA), activates a tumor-derived AR mutant (T877A), leading to androgen-independent prostate cancer cell proliferation. Here, we show that BPA cooperates with androgen to activate AR-T877A as shown by both reporter assays and increased levels of prostate-specific antigen expression. Further investigations using both yeast and mammalian model systems revealed that multiple AR alleles are responsive to BPA, thus expanding the potential influence of xenoestrogens on prostate cancer. Moreover, in vitro radioligand binding assay revealed that BPA alters 5alpha-dihydrotestosterone binding to AR-T877A likely through noncompetitive inhibition. We also show that higher concentrations of BPA block proliferation of AR-positive, androgen-dependent prostate adenocarcinoma cells (LNCaP and LAPC-4), with a more modest inhibitory effect on androgen-independent cells (22Rv-1). By contrast, AR-negative prostate cancer cells failed to show growth inhibition after exposure to high BPA dose. Together, these data show that BPA can serve as a potential "hormone sensitizer" of the mutant ARs present in advanced prostate adenocarcinomas, thereby possibly contributing toward therapeutic relapse in advanced prostate cancer patients and supporting the notion that nonsteroidal environmental compounds can alter the function of nuclear receptor complexes.
Exertion injuries in adolescent athletes.
Authors: S. Orava, J. Puranen
Journal: British Journal of Sports Medicine (1978)

A series of 147 cases of exertion injuries in less than or equal to 15 years old athletes is presented. All injuries occurred during training or athletic performances without trauma and caused symptoms that prevented athletic exercises. There were 67 girls (46%) and 80 boys (54%) in the material. About 90% of them had been training for more than one year before the onset of the symptoms; 65% were interested in track and field athletics, 13% in ball games, 11% in skiing, 4% in swimming, and 3% in orienteering. The rest were interested in other sports. About 33% of the injuries were growth disturbances or osteochondroses seen also in other children. About 15% were anomalies, deformities or earlier osteochondritic changes, which caused first symptoms during the physical exercise; 50% were typical overuse injuries that may bother adult athletes, too; 43% of the injuries were localized in ankle, foot and heel, 31% in knee, 8% in back and trunk, 7% in pelvic and hip region, and the rest in other parts of the body. The injuries were generally slight, no permanent disability was noticed. Rest and conservation therapy cured most cases; operative treatment was used in only eight cases.
Toward Defining a Cutoff Score for Elevated Fear of Hypoglycemia on the Hypoglycemia Fear Survey Worry Subscale in Patients With Type 2 Diabetes
Authors: Tibor R.S. Hajós, William H. Polonsky, Frans Pouwer, Linda Gonder-Frederick, Frank J. Snoek
Journal: Diabetes Care (2013)

OBJECTIVE To determine a cutoff score for clinically meaningful fear of hypoglycemia (FoH) on the Hypoglycemia Fear Survey Worry subscale (HFS-W). RESEARCH DESIGN AND METHODS Data on the HFS-W, history of hypoglycemia, emotional well-being (World Health Organization-5 well-being index), and distress about diabetes symptoms (Diabetes Symptom Checklist-Revised) were available from Dutch patients with type 2 diabetes who were treated with oral medication or insulin (n = 1,530). Four criteria were applied to define a threshold for clinically meaningful FoH: 1) modal score distribution (MD criterion), 2) scores 2 SDs above the mean (SD criterion), 3) concurrent validity with severe hypoglycemia and suboptimal well-being (CV criterion), and 4) an elevated score (≥3) on more than one HFS-W item (elevated item endorsement [EI criterion]). Associations between the outcomes of these approaches and a history of severe hypoglycemia and suboptimal well-being were studied. RESULTS Of the 1,530 patients, 19% had a HFS-W score of 0 (MD criterion), and 5% reported elevated FoH (HFS-W ≥ mean + 2 SD; SD criterion). Patients with severe hypoglycemia reported higher HFS-W scores than those without (25 ± 20 vs. 15 ± 17; P < 0.001). Patients with suboptimal well-being reported higher HFS-W scores than those with satisfactory well-being (20 ± 18 vs. 13 ± 15; P < 0.001, CV criterion). Elevated FoH (defined by the EI criterion) was seen in 26% of patients. The SD and EI criteria were the strongest associated with history of severe hypoglycemia. The EI criterion was the strongest associated with suboptimal well-being. CONCLUSIONS Although no definite cutoff score has been determined, the EI criterion may be most indicative of clinically relevant FoH in this exploratory study. Further testing of the clinical relevance of this criterion is needed.
Survival Effect of Maximal Cytoreductive Surgery for Advanced Ovarian Carcinoma During the Platinum Era: A Meta-Analysis
Authors: Robert E. Bristow, Rafael S. Tomacruz, Deborah K. Armstrong, Edward L. Trimble, F. J. Montz
Journal: Journal of Clinical Oncology (2002)

To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy.
Multislice Computed Tomography Angiography for Noninvasive Assessment of the 18-Month Performance of a Novel Radiolucent Bioresorbable Vascular Scaffolding Device
Authors: Koen Nieman, Patrick W. Serruys, Yoshinobu Onuma, Robert-Jan van Geuns, Hector M. Garcia-Garcia, Bernard de Bruyne, Leif Thuesen, Pieter C. Smits, Jacques J. Koolen, Dougal McClean, Bernard Chevalier, Ian Meredith, John Ormiston
Journal: Journal of the American College of Cardiology (2013)