tbuckley/cabot-search huggingface dataset:
Prospective Study of Determinants and Outcomes of Deferred Treatment or Watchful Waiting Among Men With Prostate Cancer in a Nationwide Cohort
Authors: William V. Shappley, Stacey A. Kenfield, Julie L. Kasperzyk, Weiliang Qiu, Meir J. Stampfer, Martin G. Sanda, June M. Chan
Journal: Journal of Clinical Oncology (2009)

To examine consequences of deferred treatment (DT) as initial management of prostate cancer (PCa) in a contemporary, prospective cohort of American men diagnosed with PCa.We evaluated deferred treatment for PCa in the Health Professionals Follow-up Study, a prospective study of 51,529 men. Cox proportional hazards models were used to calculate hazard ratios (HRs) for time to eventual treatment among men who deferred treatment for more than 1 year after diagnosis. HRs for time to metastasis or death as a result of PCa were compared between patients who deferred treatment and those who underwent immediate treatment within 1 year of diagnosis.From among 3,331 cohort participants diagnosed with PCa from 1986 to 2007, 342 (10.3%) initially deferred treatment. Of these, 174 (51%) remained untreated throughout follow-up (mean 7.7 years); the remainder were treated an average of 3.9 years after diagnosis. Factors associated with progression to treatment among DT patients included younger age, higher clinical stage, higher Gleason score, and higher prostate-specific antigen at diagnosis. We observed similar rates for development of metastases (n = 20 and n = 199; 7.2 v 8.1 per 1,000 person-years; P = .68) and death as a result of PCa (n = 8 and n = 80; 2.4 v 2.6 per 1,000 person-years; P = .99) for DT and immediate treatment, respectively.In this nationwide cohort, more than half the men who opted for DT remained without treatment for 7.7 years after diagnosis. Older men and men with lesser cancer severity at diagnosis were more likely to remain untreated. PCa mortality did not differ between DT and active treatment patients.
Tennis in hot and cool conditions decreases the rapid muscle torque production capacity of the knee extensors but not of the plantar flexors
Authors: Olivier Girard, Sébastien Racinais, Julien D Périard
Journal: British Journal of Sports Medicine (2014)

Objectives To assess the time course of changes in rapid muscle force/torque production capacity and neuromuscular activity of lower limb muscles in response to prolonged (∼2 h) match-play tennis under heat stress. Methods The rates of torque development (RTD) and electromyographic activity (EMG; ie, root mean square) rise were recorded from 0 to 30, –50, –100 and –200 ms during brief (3–5 s) explosive maximal isometric voluntary contractions (MVC) of the knee extensors (KE) and plantar flexors (PF), along with the peak RTD within the entirety of the torque-time curve. These values were recorded in 12 male tennis players before (prematch) and after (postmatch, 24 and 48 h) match-play in HOT (∼37°C) and COOL (∼22°C) conditions. Results The postmatch core temperature was greater in the HOT (∼39.4°C) vs COOL (∼38.7°C) condition (p&lt;0.05). Reductions in KE RTD occurred within the 0–200 ms epoch after contraction onset postmatch and at 24 h, compared with prematch, independent of environmental conditions (p&lt;0.05). A similar reduction in the KE peak RTD was also observed postmatch relative to prematch (p&lt;0.05). No differences in KE RTD values were observed after normalisation to MVC torque. Furthermore, the rate of KE EMG activity rise remained unchanged. Conversely, the PF contractile RTD and rate of EMG activity rise were unaffected by the exercise or environmental conditions. Conclusions In the KE, a reduction in maximal torque production capacity following prolonged match-play tennis appears to account for the decrease in the rate of torque development, independent of environmental conditions, while remaining unchanged in the PF.
Angiotensin-Converting Enzyme Inhibition but not Angiotensin II Receptor Blockade Regulates Matrix Metalloproteinase Activity in Patients with Glomerulonephritis
Authors: Nadège Lods, Paolo Ferrari, Felix J. Frey, Andreas Kappeler, Celine Berthier, Bruno Vogt, Hans-Peter Marti
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Equivalent long-term effects on the kidney are attributed to angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB). Nevertheless, it is unknown to which degree effects of these compounds on individual inflammatory mediators, including matrix metalloproteinases (MMP), are comparable. On the basis of structural and functional differences, it was hypothesized that ACEI and ARB differentially regulate MMP activity. In a randomized, prospective crossover trial, the effect of an ACEI (fosinopril; 20 mg/d) and of an ARB (irbesartan; 150 mg/d) on MMP activity was evaluated. Ten hypertensive patients with glomerulonephritis and normal or mildly reduced creatinine clearance were studied. MMP activity and tissue inhibitors of metalloproteinase (TIMP) levels were analyzed in serum and urine: without therapy, with ACEI, with ARB, and with both agents combined. Treatment periods continued for 6 wk separated by periods of 4 wk each without therapy. Untreated patients with glomerulonephritis displayed distinctively higher serum levels of MMP-2 but much lower MMP-1/-8/-9 concentrations compared with healthy control subjects. Immunohistology of MMP-2 and MMP-9 in kidney biopsy specimen was accordingly. However, these patients excreted higher amounts of MMP-2 and MMP-9 in urine than healthy control subjects, possibly reflecting ongoing glomerular inflammation. In patients with glomerulonephritis, ACEI significantly reduced overall MMP serum activity to 25%, whereas ARB did not show any effect. Activities of MMP-1/-2/-8/-9 were also significantly inhibited by fosinopril but not by irbesartan. Levels of TIMP-1/-2 remained unaffected. In conclusion, ACEI and ARB differentially regulate MMP activity, which may ultimately have consequences in certain types of MMP-dependent glomerulonephritis. E-mail: hpmarti@bluewin.ch
Which came first: Infants learning language or motherese?
Authors: Heather Bortfeld
Journal: Behavioral and Brain Sciences (2004)

Although motherese may facilitate language acquisition, recent findings indicate that not all aspects of motherese are necessary for word recognition and speech segmentation, the building blocks of language learning. Rather, exposure to input that has prosodic, phonological, and statistical consistencies is sufficient to jump-start the learning process. In light of this, the infant-directedness of the input might be considered superfluous, at least insofar as language acquisition is concerned.
Genetic Polymorphisms Associated with a Prolonged Progression-Free Survival in Patients with Metastatic Renal Cell Cancer Treated with Sunitinib
Authors: Astrid A.M. van der Veldt, Karel Eechoute, Hans Gelderblom, Jourik Gietema, Henk-Jan Guchelaar, Nielka P. van Erp, Alfons J.M. van den Eertwegh, John B. Haanen, Ron H.J. Mathijssen, Judith A.M. Wessels
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The objective of this study was to identify genetic polymorphisms related to the pharmacokinetics and pharmacodynamics of sunitinib that are associated with a prolonged progression-free survival (PFS) and/or overall survival (OS) in patients with clear-cell metastatic renal cell cancer (mRCC) treated with sunitinib. Experimental design: A retrospective multicenter pharmacogenetic association study was performed in 136 clear-cell mRCC patients treated with sunitinib. A total of 30 polymorphisms in 11 candidate genes, together with clinical characteristics were tested univariately for association with PFS as primary and OS as secondary outcome. Candidate variables with P &amp;lt; 0.1 were analyzed in a multivariate Cox regression model. Results: Multivariate analysis showed that PFS was significantly improved when an A-allele was present in CYP3A5 6986A/G [hazard ratio (HR), 0.27; P = 0.032], a CAT copy was absent in the NR1I3 haplotype (5719C/T, 7738A/C, 7837T/G; HR, 1.76; P = 0.017) and a TCG copy was present in the ABCB1 haplotype (3435C/T, 1236C/T, 2677G/T; HR, 0.52; P = 0.033). Carriers with a favorable genetic profile (n = 95) had an improved PFS and OS as compared with noncarriers (median PFS and OS: 13.1 versus 7.5 months and 19.9 versus 12.3 months). Next to the genetic variants, the Memorial Sloan-Kettering Cancer Center prognostic criteria were associated with PFS and OS (HR, 1.99 and 2.27; P &amp;lt; 0.001). Conclusions: This exploratory study shows that genetic polymorphisms in three genes involved in sunitinib pharmacokinetics are associated with PFS in mRCC patients treated with this drug. These findings advocate prospective validation and further elucidation of these genetic determinants in relation to sunitinib exposure and efficacy. Clin Cancer Res; 17(3); 620–9. ©2010 AACR.
Refractory coeliac sprue is a diffuse gastrointestinal disease
Authors: V Verkarre
Journal: Gut (2003)

B cells generate high-affinity antibodies within induced microanatomical structures called germinal centers (GCs). Each GC is, in essence, a Darwinian microcosm, in which B cells undergo consecutive rounds of division, hypermutation, and selection based on antigen affinity. The consensus has been that this selection is governed by T follicular helper (Tfh) cell signals, determined by the amount of cognate peptide presented by B cells on major histocompatibility complex (MHC) class II. This view was recently challenged by observations in a foreign antigen model system suggesting that peptide-MHCII density dictates the degree of initial GC entry, but does not impact B cell selection once in the GC. GCs are central to the development of pathogenic autoantibodies in a breadth of autoimmune diseases, but it is unclear to what extent autoreactive GC behavior mimics that of foreign-antigen-reactive GCs. The question of peptide-MHCII in autoreactive GC fitness is particularly relevant because the linked recognition requirement provides a safeguard against inadvertent autoreactivity. Accordingly, we investigated the role of peptide-MHCII density in self-reactive GC B cell selection in a chimeric mouse model of epitope spreading. Bone marrow chimeras were generated, in which either MHCII null/b or MHCII null/null cells were competing with MHCII b/b cells for participation in chronic autoreactive GCs. Flow cytometry and confocal analysis of GCs revealed that whereas complete MHCII deficiency blocked B cell participation in the GC, partial MHCII deficiency had only a minor impact on GC fitness. Thus, our results confirm, in an autoreactive setting, the recently reported observation of MHCII haplosufficiency in foreign antigen responses.
Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat
Authors: E. P CARROLL, J. S JANICKI, R. PICK, K. T WEBER
Journal: Cardiovascular Research (1989)

Journal Article Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat Get access EUGENIA P CARROLL, EUGENIA P CARROLL From the Cardiovascular Institute, Michael Reese Hospital and Medical Center, University of Chicago Pritzker School of Medicine, Chicago, USA Address for correspondence and reprints: Dr Karl T Weber, Michael Reese Hospital and Medical Center, Lake Shore Drive at 31st Street, Chicago, Illinois 60616, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar JOSEPH S JANICKI, JOSEPH S JANICKI From the Cardiovascular Institute, Michael Reese Hospital and Medical Center, University of Chicago Pritzker School of Medicine, Chicago, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar RUTH PICK, RUTH PICK From the Cardiovascular Institute, Michael Reese Hospital and Medical Center, University of Chicago Pritzker School of Medicine, Chicago, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar KARL T WEBER KARL T WEBER From the Cardiovascular Institute, Michael Reese Hospital and Medical Center, University of Chicago Pritzker School of Medicine, Chicago, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 8, August 1989, Pages 655–661, https://doi.org/10.1093/cvr/23.8.655 Published: 01 August 1989 Article history Accepted: 01 February 1989 Published: 01 August 1989
Validation of Measurement Scales in Ocular Graft-versus-Host Disease
Authors: Yoshihiro Inamoto, Xiaoyu Chai, Brenda F. Kurland, Corey Cutler, Mary E.D. Flowers, Jeanne M. Palmer, Paul A. Carpenter, Mary J. Heffernan, David Jacobsohn, Madan H. Jagasia, Joseph Pidala, Nandita Khera, Georgia B. Vogelsang, Daniel Weisdorf, Paul J. Martin, Steven Z. Pavletic, Stephanie J. Lee
Journal: Ophthalmology (2011)
Physical and Functional Association of the Src Family Kinases Fyn and Lyn with the Collagen Receptor Glycoprotein VI-Fc Receptor γ Chain Complex on Human Platelets
Authors: Yasuharu Ezumi, Keisuke Shindoh, Masaaki Tsuji, Hiroshi Takayama
Journal: The Journal of Experimental Medicine (1998)

We have previously shown that uncharacterized glycoprotein VI (GPVI), which is constitutively associated and coexpressed with Fc receptor γ chain (FcRγ) in human platelets, is essential for collagen-stimulated tyrosine phosphorylation of FcRγ, Syk, and phospholipase Cγ2 (PLCγ2), leading to platelet activation. Here we investigated involvement of the Src family in the proximal signals through the GPVI–FcRγ complex, using the snake venom convulxin from Crotalus durissus terrificus, which specifically recognizes GPVI and activates platelets through cross-linking GPVI. Convulxin-coupled beads precipitated the GPVI–FcRγ complex from platelet lysates. Collagen and convulxin induced tyrosine phosphorylation of FcRγ, Syk, and PLCγ2 and recruited tyrosine-phosphorylated Syk to the GPVI–FcRγ complex. Using coprecipitation methods with convulxin-coupled beads and antibodies against FcRγ and the Src family, we showed that Fyn and Lyn, but not Yes, Src, Fgr, Hck, and Lck, were physically associated with the GPVI–FcRγ complex irrespective of stimulation. Furthermore, Fyn was rapidly activated by collagen or cross-linking GPVI. The Src family–specific inhibitor PP1 dose-dependently inhibited collagen- or convulxin-induced tyrosine phosphorylation of proteins including FcRγ, Syk, and PLCγ2, accompanied by a loss of aggregation and ATP release reaction. These results indicate that the Src family plays a critical role in platelet activation via the collagen receptor GPVI–FcRγ complex.
Phenethyl Isothiocyanate, a Cancer Chemopreventive Constituent of Cruciferous Vegetables, Inhibits Cap-Dependent Translation by Regulating the Level and Phosphorylation of 4E-BP1
Authors: Jing Hu, Jonathan Straub, Dong Xiao, Shivendra V. Singh, Hsin-Sheng Yang, Nahum Sonenberg, Jaya Vatsyayan
Journal: Cancer Research (2007)

Abstract Phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, exerts significant protection against chemically induced cancer in animal models and inhibits growth of cancer cells in culture and in vivo by causing cell cycle arrest and apoptosis induction. In this study, we report a novel response to PEITC involving the regulation of translation initiation at pharmacologically achievable concentrations. Treatment of human colorectal cancer HCT-116 cells and human prostate cancer PC-3 cells, but not a normal prostate epithelial cell line (PrEC), with PEITC caused an increase in expression of the eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) and inhibition of 4E-BP1 phosphorylation. Results from pull-down assay using 7-methyl-GTP Sepharose 4B beads indicated that PEITC treatment reduced cap-bound eIF4E, confirming that increased 4E-BP1 expression and inhibition of 4E-BP1 phosphorylation indeed reduced the availability of eIF4E for translation initiation. Accordingly, results from in vivo translation using luciferase reporter assay indicated that PEITC treatment inhibited cap-dependent translation, in particular the translation of mRNA with secondary structure (stem-loop structure). Ectopic expression of eIF4E prevented PEITC-induced translation inhibition and conferred significant protection against PEITC-induced apoptosis. These results indicate that PEITC modulates availability of eIF4E for translation initiation leading to inhibition of cap-dependent translation. The present study also suggests that inhibition of cap-dependent translation may be an important mechanism in PEITC-induced apoptosis. [Cancer Res 2007;67(8):3569–73]
Enhanced Proteoglycan Deposition in the Airway Wall of Atopic Asthmatics
Authors: JUN HUANG, RON OLIVENSTEIN, RAME TAHA, QUTAYBA HAMID, MARA LUDWIG
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Increased extracellular matrix (ECM) deposition in the airway wall contributes to the airway wall remodeling observed in asthmatics. Although alterations in collagen have been well described, less is known about changes in other components of the ECM, particularly proteoglycans (PGs). Endobronchial biopsies were obtained from seven patients with mild atopic asthma and six normal control subjects. Tissues were blocked in OCT and frozen in isopentane. Sections were immunostained with antibodies for the small leucine-rich PGs, lumican, biglycan, decorin, and fibromodulin and for versican, a large chondroitin sulfate PG. We calculated the area of positive staining in the subepithelial layer, correcting for basement membrane length. Lumican, biglycan, and versican were localized predominantly in the subepithelial layer of the airway wall in all groups. PG deposition was significantly increased in asthmatics as compared with that in control subjects. Furthermore, the degree of PG immunoreactivity was significantly correlated with airway responsiveness in the asthmatics (lumican; r = − 0.77, p < 0.05; biglycan: r = − 0.76, p < 0.05; versican: r = − 0.74, p = 0.06). Our results suggest that PGs may play a role in airway wall remodeling and thereby, airway mechanics in asthma.
Parental smoking impairs vaccine responses in children with atopic genotypes
Authors: Gareth Baynam, Siew-Kim Khoo, Julie Rowe, Guicheng Zhang, Ingrid Laing, Catherine Hayden, Merci Kusel, Nick DeKlerk, Peter Sly, Jack Goldblatt, Patrick Holt, Peter LeSouef
Journal: Journal of Allergy and Clinical Immunology (2006)
Hereditary mucoepithelial dysplasia: clinical, ultrastructural and genetic study of eight patients and literature review
Authors: F. Boralevi, M. Haftek, P. Vabres, S. Lepreux, C. Goizet, C. Leaute-Labreze, A. Taieb
Journal: British Journal of Dermatology (2005)

Hereditary mucoepithelial dysplasia is a dominantly inherited disease, mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo. Since the original report by Witkop, this condition has been considered to be a disorder of desmosome/gap junction formation, but there has been no ex vivo investigation of these components using genetic and immunolabelling techniques.To perform light and immunoelectron microscopic studies, and partial genetic analysis on five patients in a family and three sporadic cases and to point out similarities of this rare disorder with chronic mucocutaneous candidiasis and other follicular keratosis syndromes, i.e. ichthyosis follicularis-alopecia-photophobia (IFAP), keratitis-ichthyosis-deafness (KID) and Siemens syndromes.Biopsies from the involved oral mucosa and armpit skin of patient 1 were prepared for standard histopathology, electron microscopy and immunocytochemistry. Microsatellite genotyping was performed in three affected family members. Direct sequencing after polymerase chain reaction amplification of the entire coding region was performed.A 14-year-old male had recurrent keratitis, widespread keratosis pilaris, perineal intertrigo, hypotrichosis and oral mucosal involvement. A similar phenotype was noted in four members of his family and in three sporadic cases. Histological examination of oral mucosa and skin samples showed a psoriasiform pattern, dyskeratotic features and cytoplasmic vacuoles. Expression of connexins (Cx), desmosomal, adherens junction and cytoskeleton proteins (Cx 26, 32 and 43, desmogleins 1 and 2, plakoglobin, desmoplakins I-II, plakophilin 1, beta-catenin, E-cadherin, keratins, beta-tubulin, vimentin and actin) was normal. Ultrastructural studies showed a reduced number of desmosomes. Dyskeratotic cells exhibited internalized gap junctions, long filamentous inclusions reactive with antikeratin antibodies, and bundles of perinuclear fibres resembling clear tonofilaments. Genetic analysis in the studied family excluded the desmosomal cadherins in chromosome 18q12 as candidate genes.A diagnosis of hereditary mucoepithelial dysplasia should be strongly suggested by the triad of non-scarring alopecia, well-demarcated erythema of oral mucosa and psoriasiform perineal rash, after exclusion of the clinically related follicular keratosis syndromes. Defective expression of cytoskeleton elements and/or a modification of mechanisms regulating junction-cytoskeleton assembly may be primarily responsible for impaired epithelial cohesion.
Immunological and physiological characteristics of the rapid immune hemolysis of neuraminidase-treated sheep red cells produced by fresh guinea pig serum.
Authors: P K Lauf
Journal: The Journal of Experimental Medicine (1975)

The rapid hemolysis by fresh guinea pig serum known to occur with neuraminidase-treated sheep red cells has been investigated with respect to the immunological and physiological properties of the lytic process. The following observations were made: (a) The susceptibility to hemolysis is directly proportional to the amounts of neuraminic acid enzymatically released from the cell surface. Complement lysis is mediated through binding of an IgM antibody protein to membranes of neuraminidase-treated cells. (b) Hemolysis is relatively temperature-independent above about 28 degrees C but below which a decrease in the hemolysis rate occurs. Arrhenius activation energies above and below the transition temperature were therefore found to be different. (c) Colloid osmotic swelling of neuraminidase-treated high potassium sheep red cells with a chloride ion concentration ratio near unity suspended in high potassium medium could not be prevented by sucrose. Hence, colloid osmotic swelling before lysis must be due to the entrance of sucrose and water since sucrose was the only external solute not at equilibrium. (d) From the rate of swelling and the apparent flux of sucrose under nonsteady state conditions an experimental permeability coefficient (P) for sucrose of 3-10(-8) cm-s-1 was computed. Comparison with a theoretical P of 4-10(-6) cm-s-1 for sucrose freely permeating through a single, hypothetical membrane lesion per cell of 60 A effective diameter indicates a membrane lesion which permits the passage of solutes larger than cations, but clearly constrains the free diffusion of sucrose.