tbuckley/cabot-search huggingface dataset:
The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4+ T cells
Authors: C.E.M. GRIFFITHS, D. RAILAN, W.M. GALLATIN, K.D. COOPER
Journal: British Journal of Dermatology (1995)

Intercellular adhesion molecule (ICAM)‐3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM‐1 and ICAM‐2. All three ICAMS are cognate for the counter‐receptor lymphocyte function associated antigen‐1 (LFA‐L CD11a/CD18). Unlike ICAM‐1 and ICAM‐2. ICAM‐3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM‐3 in normal skin (n= 5), as well as its expression in psoriasis (n= 4). atopic eczema (n= 4), allergic (rhus) contact dermatitis (n=3). and cutaneous T‐cell lymphoma (CTCL. n=2). Five‐micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM‐3 and A well characterized immunoperoxidase technique. In normal skin. ICAM‐3 was expressed by all cutaneous leucocytes hut most striking was the strong expression of ICAM‐3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double‐labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL. ICAM‐3 was co‐expressed on all CD1a+ cells, although, in psoriasis, the intensity of ICAM‐3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM‐3 expression on Langerhans cells was functionally important in antigen presentation. CD4+ T cells were prepared from peripheral blood and 105 CD4+ T cells combined with 105 epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T‐cell donor. Addition of 50 μg anti‐ICAM‐3 to the co‐culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti‐LFA‐1. These data indicate that ICAM‐3 is constitutively expressed by Langerhans cells and is a major ligand for LFA‐1 on CD4+ T cells during their response to Langerhans cells. Because fresh Langerhans ceils constitutively express little ICAM‐1. whereas ICAM‐3 is constitutively expressed at high levels, it would appear that 1CAM‐3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.
The Ejection Click of Valvular Pulmonic Stenosis
Authors: HERBERT N. HULTGREN, RICHARD REEVE, KEITH COHN, RIMA MCLEOD
Journal: Circulation (1969)

Ten patients with valvular pulmonic stenosis were studied by simultaneous external phonocardiograms and intracardiac pressure recordings during successive respiratory cycles to examine the mechanism of the respiratory variation in the ejection click. Selective cineangiograms were performed in four. During inspiration right ventricular end-diastolic pressure (RVEDP) exceeded the pressure in the pulmonary artery (+2.7 mm) and no ejection click was recorded. During expiration RVEDP was lower than the pressure in the pulmonary artery (-3.6 mm) and a click was recorded. The click was present throughout the respiratory cycle when pulmonary artery diastolic pressure consistently exceeded RVEDP. Clicks were associated with sudden "doming" of the valve demonstated by cineangiography. These data support the valvular origin of the ejection click in pulmonic stenosis and provide the following explanation for the respiratory variation: Inspiratory increase in venous return causes the valve leaflets to move to an open or "domed" position. Ventricular systole at this time produces no sound since there is no slack. With expiration pulmonary artery pressure exceeds RVEDP. Ventricular systole at this time produces an opening motion of the closed, slack leaflets. The click occurs when the opening motion is suddenly checked.
Another route to broadening the scope of social psychology: Ecologically valid research
Authors: Samuel D. Gosling
Journal: Behavioral and Brain Sciences (2004)

An imbalance is identified in social psychology between controlled experimental studies (which are common) and real-world, ecologically valid studies (which are rare). The preponderance of experimental studies (which provide mere existence proofs and lack realism) helps fuel social psychology's fault-finding focus. Laboratory experiments and ecological studies should be pursued jointly to examine social life in the real world.
Addition of fexofenadine to a topical corticosteroid reduces the pruritus associated with atopic dermatitis in a 1-week randomized, multicentre, double-blind, placebo-controlled, parallel-group study
Authors: M. Kawashima, T. Tango, T. Noguchi, M. Inagi, H. Nakagawa, S. Harada
Journal: British Journal of Dermatology (2003)

Fexofenadine, a nonsedating, H1-receptor selective antihistamine, exhibits consistent efficacy and safety in the treatment of allergic rhinitis and urticaria. The pruritus associated with atopic dermatitis is considered to be induced, in part, by histamine. Therefore, we thought that fexofenadine may be useful in the relief of pruritus associated with atopic dermatitis.To compare the efficacy of twice-daily fexofenadine hydrochloride (HCl) 60 mg vs. placebo in reducing the pruritus associated with atopic dermatitis.In this randomized, multicentre, double-blind, placebo-controlled study, patients (aged >or= 16 years) with atopic dermatitis underwent a 1-week placebo lead-in period, followed by randomization to fexofenadine HCl 60 mg twice daily or placebo for 1 week. All patients also received topical treatment with 0.1% hydrocortisone butyrate twice daily throughout the study. The primary efficacy endpoint was mean change in pruritus score from baseline. Patients reflectively recorded pruritus scores twice daily (day and night) using a five-point scale (0 = none; 4 = very severe).Fexofenadine (n = 201) significantly decreased the severity of pruritus compared with placebo (n = 199) (mean change in score -0.75 (unadjusted 95% confidence interval [-0.88, -0.62]) vs. -0.5 [-0.62, -0.38], respectively; P = 0.0005). This improvement was seen after just 1 day of treatment (P = 0.039) and was maintained throughout the treatment period (P = 0.019). Compared with placebo, fexofenadine significantly improved both diurnal (P = 0.0001) and nocturnal pruritus (P = 0.013). In addition, significantly more patients in the fexofenadine group experienced a reduction in the ratio of pruritus area to body surface area compared with those in the placebo group (P = 0.007). The incidence of adverse events was low and similar across all treatment groups.Fexofenadine HCl 60 mg twice daily demonstrated a rapid, significant improvement in the pruritus associated with atopic dermatitis, with a safety profile equivalent to that of placebo.
A validated tool to predict colorectal neoplasia and inform screening choice for asymptomatic subjects
Authors: Martin C S Wong, Thomas Y T Lam, Kelvin K F Tsoi, Hoyee W Hirai, Victor C W Chan, Jessica Y L Ching, Francis K L Chan, Joseph J Y Sung
Journal: Gut (2013)

<h3>Objective</h3> We aim to develop and validate a clinical scoring system to predict the risks of colorectal neoplasia to better inform screening participants and facilitate their screening test choice. <h3>Design</h3> We recruited 5220 Chinese asymptomatic screening participants who underwent colonoscopy in Hong Kong during 2008–2012. From random sampling of 2000 participants, independent risk factors were evaluated for colorectal neoplasia, defined as adenoma, advanced neoplasia, colorectal cancer or any combination thereof using binary regression analysis. The ORs for significant risk factors were used to develop a scoring system ranging from 0 to 6: 0–2 'average risk' (AR) and 3–6 'high risk' (HR). The other 3220 screening participants prospectively enrolled between 2008 and 2012 for screening colonoscopy formed an independent validation cohort. The performance of the scoring system for predicting colorectal neoplasia was evaluated. <h3>Results</h3> The prevalence of colorectal neoplasia in the derivation and validation cohorts was 31.4% and 30.8%, respectively. Using the scoring system developed, 78.9% and 21.1% in the validation cohort were classified as AR and HR, respectively. The prevalence of colorectal neoplasia in the AR and HR groups was 27.1% and 44.6%, respectively. The subjects in the HR group had 1.65-fold (95% CI 1.49 to 1.83) increased prevalence of colorectal neoplasia than the AR group. <h3>Conclusions</h3> The scoring system based on age, gender, smoking, family history, Body Mass Index and self-reported diabetes is useful in predicting the risk of colorectal neoplasia.
Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence
Authors: P. M. Matricardi, S. Illi, C. Gruber, T. Keil, R. Nickel, U. Wahn, S. Lau
Journal: European Respiratory Journal (2008)

Childhood asthma is frequently perceived as a disease with uniform clinical pathways. This perception might be an oversimplification. The aim of the present study was to investigate the incidence and natural course of wheeze over the first 13 yrs of life and analyse the risk factors predicting wheeze at 11–13 yrs of age. The Multicentre Allergy Study, a German birth cohort, recruited 1,314 children in 1990. Physical examinations, interviews on atopic diseases, immunoglobulin (Ig)E and lung function tests were performed up to 13 yrs of age. Complete data on the course of wheeze were available for 441 children. It was found that incidence of wheezing declined with age. The first wheezing episode was reported by 29, 9 and 9% of participants at ≤3 (early wheezers), 3–6 (late wheezers), and &gt;6 yrs (very late wheezers) of age, respectively. Wheezing at the age of 13 yrs was associated with parental atopy, and with IgE sensitisation to common allergens, elevated total IgE and exposure to high levels of indoor allergens in early life. All these associations were remarkably stronger among early wheezers than among early nonwheezers. In conclusion, the relevance of an early expression of atopy as a predictor of wheezing at age 13 yrs declines with increasing age of wheezing onset.
Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.
Authors: J D Veldhuis, M L Johnson, L M Faunt, M Mercado, G Baumann
Journal: Journal of Clinical Investigation (1993)

The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein would damp sharp oscillations in GH concentrations otherwise caused by bursts of GH secretion into the blood volume, prolong the apparent half-life of circulating GH, and contribute a reservoir function. To test these implicit considerations, we formulated an explicit mathematical model of pulsatile GH secretion and clearance in the presence of absence of a specific high-affinity GH-BP. Simulation experiments revealed that the pulsatile mode of physiological GH secretion creates a highly dynamic (nonequilibrium) system, in which the half-life of free GH, its instantaneous secretion rate, and the GH-BP affinity and capacity all contribute to defining momentary levels of free, bound, and total GH, the percentage of GH bound to protein, and the percentage occupancy of GH-BP [corrected]. In contrast, the amount of free GH at equilibrium is specified only by the GH distribution volume and secretion rate and the half-life of free hormone. We conclude that the in vivo dynamics of GH secretion, trapping, and clearance from the circulation offer a variety of regulatory loci at which the time structure of free, bound, and total GH delivery to target tissues can be controlled physiologically.
Aflibercept and Docetaxel Versus Docetaxel Alone After Platinum Failure in Patients With Advanced or Metastatic Non–Small-Cell Lung Cancer: A Randomized, Controlled Phase III Trial
Authors: Rodryg Ramlau, Vera Gorbunova, Tudor Eliade Ciuleanu, Silvia Novello, Mustafa Ozguroglu, Tuncay Goksel, Clarissa Baldotto, Jaafar Bennouna, Frances A. Shepherd, Solenn Le-Guennec, Augustin Rey, Vincent Miller, Nicholas Thatcher, Giorgio Scagliotti
Journal: Journal of Clinical Oncology (2012)

To compare the efficacy of aflibercept (ziv-aflibercept), a recombinant human fusion protein targeting the vascular endothelial growth factor (VEGF) pathway, with or without docetaxel in platinum-pretreated patients with advanced or metastatic nonsquamous non-small-cell lung cancer.In this international, double-blind, placebo-controlled phase III trial, 913 patients were randomly assigned to (ziv-)aflibercept 6 mg/kg intravenous (IV; n = 456) or IV placebo (n = 457), both administered every 3 weeks and in combination with docetaxel 75 mg/m(2). The primary end point was overall survival (OS). Other efficacy outcomes, safety, and immunogenicity were also assessed.Patient characteristics were balanced between arms; 12.3% of patients had received prior bevacizumab. (Ziv-)Aflibercept did not improve OS (hazard ratio [HR], 1.01; 95% CI, 0.87 to 1.17; stratified log-rank P = .90). The median OS was 10.1 months (95% CI, 9.2 to 11.6 months) for (ziv-)aflibercept and 10.4 months (95% CI, 9.2 to 11.9 months) for placebo. In exploratory analyses, median progression-free survival was 5.2 months (95% CI, 4.4 to 5.6 months) for (ziv-)aflibercept versus 4.1 months (95% CI, 3.5 to 4.3 months) for placebo (HR, 0.82; 95% CI, 0.72 to 0.94; P = .0035); overall response rate was 23.3% of evaluable patients (95% CI, 19.1% to 27.4%) in the (ziv-)aflibercept arm versus 8.9% (95% CI, 6.1% to 11.6%; P < .001) in the placebo arm. Grade ≥ 3 adverse events occurring more frequently in the (ziv-)aflibercept arm versus the placebo arm were neutropenia (28.0% v 21.1%, respectively), fatigue (11.1% v 4.2%, respectively), stomatitis (8.8% v 0.7%, respectively), and hypertension (7.3% v 0.9%, respectively).The addition of (ziv-)aflibercept to standard docetaxel therapy did not improve OS. In exploratory analyses, secondary efficacy end points did seem to be improved in the (ziv-)aflibercept arm. The study regimen was associated with increased toxicities, consistent with known anti-VEGF and chemotherapy-induced events.
Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells
Authors: Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Lin Cui, Kazuhiro Mizumoto, Masao Tanaka
Journal: Cancer Research (2013)

Pancreatic stellate cells (PSC), which are implicated in desmoplasia in pancreatic cancer, enhance the malignancy of cancer cells and confer resistance to established treatments. We investigated whether the antifibrotic agent pirfenidone can suppress desmoplasia and exert antitumor effects against pancreatic cancer. Primary PSCs were established from pancreatic cancer tissue obtained during surgery. In vitro, pirfenidone inhibited the proliferation, invasiveness, and migration of PSCs in a dose-dependent manner. Although supernatants of untreated PSCs increased the proliferation, invasiveness, and migration of pancreatic cancer cells (PCC), supernatants of pirfenidone-treated PSCs decreased these effects. Exposure to PCC supernatant increased the production of platelet-derived growth factor-A, hepatic growth factor, collagen type I, fibronectin, and periostin in PSCs, which was significantly reduced by pirfenidone. Mice were subcutaneously implanted with PCCs (SUIT-2 cells) and PSCs into the right flank and PCCs alone into the left flank. Oral administration of pirfenidone to these mice significantly reduced tumor growth of co-implanted PCCs and PSCs, but not of PCCs alone. Pirfenidone also decreased the proliferation of PSCs and the deposition of collagen type I and periostin in tumors. In mice with orthotopic tumors consisting of PCCs co-implanted with PSCs, pirfenidone suppressed tumor growth, reduced the number of peritoneal disseminated nodules, and reduced the incidence of liver metastasis. Pirfenidone in combination with gemcitabine more effectively suppressed orthotopic tumor growth compared with pirfenidone or gemcitabine alone. In conclusion, our findings indicate that pirfenidone is a promising antitumor agent for pancreatic cancer, owing to its suppression of desmoplasia through regulating PSCs.
Dose and Time Response after Intraamniotic Endotoxin in Preterm Lambs
Authors: BORIS W. KRAMER, TIMOTHY J. MOSS, KAREN E. WILLET, JOHN P. NEWNHAM, PETER D. SLY, SUHAS G. KALLAPUR, MACHIKO IKEGAMI, ALAN H. JOBE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved fetal lung function after 4 d in fetal sheep. We evaluated 0.1 mg, 1 mg, 4 mg, and 10 mg endotoxin for inflammation and lung maturation effects after 7 d. Four and 10 mg endotoxin caused similar lung maturation and inflammation in the lung and chorioamnion. The number of neutrophils in cord blood and the inflammatory cells in alveolar lavage and fetal lung tissue increased in a dose-dependent manner. Lower endotoxin doses induced indicators of chorioamnionitis, lung and systemic inflammation without inducing lung maturation. Therefore, some degree of inflammation can occur without subsequent lung maturation. The inflammatory changes caused by 4 mg endotoxin were assessed after 5 h, 24 h, 72 h, and 7 d to discern local versus systemic inflammation after intraamniotic endotoxin. At 5 h active inflammatory cells were in the airways producing hydrogen peroxide, and interleukin-6 and -8 were increased in the cord blood indicating both lung and systemic responses. Cells recruited into the amniotic fluid produced proinflammatory cytokine mRNA for 7 d with no cytokine mRNA in chorioamnion, lung, or spleen after 72 h. The cells in the amniotic fluid may be a source of prolonged fetal exposure to proinflammatory cytokines.
Rational Follow-Up After Curative Cancer Resection
Authors: Matthew J. Furman, Laura A. Lambert, Mary E. Sullivan, Giles F. Whalen
Journal: Journal of Clinical Oncology (2013)

Cancer recurrence after complete resection of the primary tumor is dreaded by patients and physicians alike. Intensive follow-up after curative resection is considered a marker of good practice and frequently perceived as an antidote against recurrence by patients and families. In the United States, there is abiding faith in frequent imaging and blood tests as the best tools for the job. Thoughtful practice, clinical guidelines, retrospective reviews of prospectively gathered data, and clinical trials of follow-up have focused on the number, frequency, and sequence of modalities. A different perspective on which to predicate follow-up of patients with curatively treated cancer is to consider whether meaningful treatment options exist for recurrence. In cancers for which there are meaningful treatment options, it is reasonable to expect that moreintensive follow-up may improve survival. This commentary discusses this perspective in the context of the established literature in patients with colorectal and breast cancers, two cancers considered to have effective treatments for metastatic and recurrent disease as compared with non–small-cell lung cancer (NSCLC) and pancreatic cancer, which do not.
The use of superporous Ac-CGGASIKVAVS-OH-modified PHEMA scaffolds to promote cell adhesion and the differentiation of human fetal neural precursors
Authors: Šárka Kubinová, Daniel Horák, Nataliya Kozubenko, Václav Vaněček, Vladimír Proks, Jack Price, Graham Cocks, Eva Syková
Journal: Biomaterials (2010)
Antitumoral efficacy of adenoviral mediated gene transfer of angiostatin-like molecule in subcutaneously growing HEPA129 hepatomas in mice depends on the application modus
Authors: V. Schmitz, L. Tirado, E. Raskopf, C. Rabe, J. Prieto, C. Qian, T. Sauerbruch, W.H. Caselmann
Journal: Journal of Hepatology (2003)
Signaling From the Golgi: Mechanisms and Models for Golgi Phosphoprotein 3–Mediated Oncogenesis
Authors: Kenneth L. Scott, Lynda Chin
Journal: Clinical Cancer Research (2010)

Golgi phosphoprotein 3 (GOLPH3; also known as GPP34/GMx33/MIDAS) represents an exciting new class of oncoproteins involved in vesicular trafficking. Encoded by a gene residing on human chromosome 5p13, which is frequently amplified in multiple solid tumor types, GOLPH3 was initially discovered as a phosphorylated protein localized to the Golgi apparatus. Recent functional, cell biological, and biochemical analyses show that GOLPH3 can function as an oncoprotein to promote cell transformation and tumor growth by enhancing activity of the mammalian target of rapamycin, a serine/threonine protein kinase known to regulate cell growth, proliferation, and survival. Although its precise mode of action in cancer remains to be elucidated, the fact that GOLPH3 has been implicated in protein trafficking, receptor recycling, and glycosylation points to potential links of these cellular processes to tumorigenesis. Understanding how these processes may be deregulated and contribute to cancer pathogenesis and drug response will uncover new avenues for therapeutic intervention.
Saposin C promotes survival and prevents apoptosis via PI3K/Akt-dependent pathway in prostate cancer cells.
Authors: Tae-Jin Lee, Oliver Sartor, Ronald B Luftig, Shahriar Koochekpour
Journal: Molecular Cancer (2004)

In addition to androgens, growth factors are also implicated in the development and neoplastic growth of the prostate gland. Prosaposin is a potent neurotrophic molecule. Homozygous inactivation of prosaposin in mice has led to the development of a number of abnormalities in the male reproductive system, including atrophy of the prostate gland and inactivation of mitogen-activated protein kinase (MAPK) and Akt in prostate epithelial cells. We have recently reported that prosaposin is expressed at a higher level by androgen-independent (AI) prostate cancer cells as compared to androgen-sensitive prostate cancer cells or normal prostate epithelial and stromal cells. In addition, we have demonstrated that a synthetic peptide (prosaptide TX14A), derived from the trophic sequence of the saposin C domain of prosaposin, stimulated cell proliferation, migration and invasion and activated the MAPK signaling pathway in prostate cancer cells. The biological significances of saposin C and prosaposin in prostate cancer are not known.Here, we report that saposin C, in a cell type-specific and dose-dependent manner, acts as a survival factor, activates the Akt-signaling pathway, down-modulates caspase-3, -7, and -9 expression and/or activity, and decreases the cleaved nuclear substrate of caspase-3 in prostate cancer cells under serum-starvation stress. In addition, prosaptide TX14A, saposin C, or prosaposin decreased the growth-inhibitory effect, caspase-3/7 activity, and apoptotic cell death induced by etoposide. We also discovered that saposin C activates the p42/44 MAP kinase pathway in a pertussis toxin-sensitive and phosphatidylinositol 3-kinase (PI3K) /Akt-dependent manner in prostate cancer cells. Our data also show that the anti-apoptotic activity of saposin C is at least partially mediated via PI3K/Akt signaling pathway.We postulate that as a mitogenic, survival, and anti-apoptotic factor for prostate cancer cells, saposin C or prosaposin may contribute to prostate carcinogenesis at its early androgen-dependent or metastatic AI state.