tbuckley/cabot-search huggingface dataset:
Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury
Authors: Tara K. Sigdel, Li Li, Tim Q. Tran, Purvesh Khatri, Maarten Naesens, Poonam Sansanwal, Hong Dai, Szu-chuan Hsieh, Minnie M. Sarwal
Journal: Journal of the American Society of Nephrology (2012)

Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-γ, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.
Calcium Oxalate Crystal Adherence to Hyaluronan-, Osteopontin-, and CD44-Expressing Injured/Regenerating Tubular Epithelial Cells in Rat Kidneys
Authors: Marino Asselman, Anja Verhulst, Marc E De Broe, Carl F Verkoelen
Journal: Journal of the American Society of Nephrology (2003)

Retention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate (CaOx) crystal binding during wound healing. This concept was investigated in vivo by treating rats for 1, 4, and 8 d with ethylene glycol (0.5 and 0.75%) in their drinking water to induce renal tubular cell damage and CaOx crystalluria. Tubular injury was morphologically scored on periodic acid-Schiff-stained renal tissue sections and tissue repair assessed by immunohistochemical staining for proliferating cell nuclear antigen. CaOx crystals were visualized in periodic acid-Schiff-stained sections by polarized light microscopy, and renal calcium deposits were quantified with von Kossa staining. HA was visualized with HA-binding protein and OPN and CD44 immunohistochemically with specific antibodies and quantified with an image analyzer system. Already after 1 d of treatment, both concentrations of ethylene glycol induced hyperoxaluria and CaOx crystalluria. At this point, there was neither tubular injury nor crystal retention in the kidney, and expression of HA, OPN, and CD44 was comparable to untreated controls. After 4 and 8 d of ethylene glycol, however, intratubular crystals were found adhered to injured/regenerating (proliferating cell nuclear antigen positive) tubular epithelial cells, expressing HA, OPN, and CD44 at their luminal membrane. In conclusion, the expression of HA, OPN, and CD44 by injured/regenerating tubular cells seems to play a role in retention of crystals in the rat kidney.
The substance of cultural evolution: Culturally framed systems of social organization
Authors: Dwight W. Read
Journal: Behavioral and Brain Sciences (2014)

Abstract Models of cultural evolution need to address not only the organizational aspects of human societies, but also the complexity and structure of cultural idea systems that frame their systems of organization. These cultural idea systems determine a framework within which behaviors take place and provide mutually understood meanings for behavior from the perspective of both agent and recipient that are critical for the coherence of human systems of social organization.
Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction
Authors: Jonathan Pitcher, Anna Abt, Jaclyn Myers, Rachel Han, Melissa Snyder, Alessandro Graziano, Lindsay Festa, Michele Kutzler, Fernando Garcia, Wen-Jun Gao, Tracy Fischer-Smith, Jay Rappaport, Olimpia Meucci
Journal: Journal of Clinical Investigation (2014)

Interaction of the chemokine CXCL12 with its receptor CXCR4 promotes neuronal function and survival during embryonic development and throughout adulthood. Previous studies indicated that μ-opioid agonists specifically elevate neuronal levels of the protein ferritin heavy chain (FHC), which negatively regulates CXCR4 signaling and affects the neuroprotective function of the CXCL12/CXCR4 axis. Here, we determined that CXCL12/CXCR4 activity increased dendritic spine density, and also examined FHC expression and CXCR4 status in opiate abusers and patients with HIV-associated neurocognitive disorders (HAND), which is typically exacerbated by illicit drug use. Drug abusers and HIV patients with HAND had increased levels of FHC, which correlated with reduced CXCR4 activation, within cortical neurons. We confirmed these findings in a nonhuman primate model of SIV infection with morphine administration. Transfection of a CXCR4-expressing human cell line with an iron-deficient FHC mutant confirmed that increased FHC expression deregulated CXCR4 signaling and that this function of FHC was independent of iron binding. Furthermore, examination of morphine-treated rodents and isolated neurons expressing FHC shRNA revealed that FHC contributed to morphine-induced dendritic spine loss. Together, these data implicate FHC-dependent deregulation of CXCL12/CXCR4 as a contributing factor to cognitive dysfunction in neuroAIDS.
Factors Controlling Pacemaker Action in Cells of the Sinoatrial Node
Authors: HSIN-HSIANG LU, GERTRUDE LANGE, CHANDLER McC. BROOKS
Journal: Circulation Research (1965)

Rapid drive of isolated pacemaker tissues from cats resulted in a post-drive depression followed by a late acceleration to supernormal rates of pacemaker activity. These effects were similar to those occurring after drive of the pacemaker in situ . Lower SA nodal pacemakers discharged more slowly and irregularly than did upper SA nodal pacemaker cells. They were more readily depressed by rapid imposed drive. The balance between depression and acceleration varied in different preparations. Drive at only slightly above the intrinsic rate resulted frequently in acceleration not preceded by depression. Within limits, the greater the frequency and duration of drive, the greater the intensity and duration of both the depression and the late acceleration. Prostigmin augmented and atropine reduced post-drive depression. Cocaine potentiated the late acceleration. Excess potassium reduced post-drive depression and, in concentrations used, caused some acceleration. Pacemaker cells could be driven less rapidly than could other SA nodal cells. Drive generally shifted pacemaker action to a distant site; the first post-drive propagated responses originated from other pacemaker cells and dominance by the original unit was reestablished slowly. Rapid drive reduced amplitudes of action potentials and prepotentials. It also raised threshold potentials and during the post-drive period the durations of pacemaker cell action potentials were temporarily prolonged. In some preparations membrane potentials remained at a subnormal value after drive. Subthreshold potentials occurred at a somewhat subnormal rhythm but gradually developed an effective amplitude. Conduction block was observed in isolated SA nodal tissue. This was augmented during the post-drive period of depression. This work lends support to the hypothesis 1 that dominating action by pacemaker cells influences the pacemaker activity in other potential pacemaker tissues.
Prevention, Survivorship Highlighted in England's Cancer Plan Update
Authors: K. Travis
Journal: JNCI Journal of the National Cancer Institute (2008)

September of this year, all 12- and 13-yearold girls will receive the HPV vaccine. The following year, the health service will provide a catch-up program for girls up to the age of 18 who haven’t received the vaccine for HPV. Unlike prevention, cancer survivorship was largely absent from the original cancer plan. To that end, the reform strategy announced the creation of a national cancer survivorship initiative that will connect government, cancer charities, doctors, and patients to improve services for people living with cancer. “It’s going to bring all major stakeholders together to try to understand these models of followup better and try to work out how we can develop more personalized care for cancer survivors,” Foot said. Part of improving survivorship is understanding the factors that contribute to it. Cancer survival rates in England are fairly low compared with those in the rest of Europe — on par with Eastern European countries that spend far less on cancer care, according to last September’s EUROCARE-4 study, a pan-European comparison of cancer rates. A major reason for the low survival rates, Foot said, is late diagnosis. At issue is “what can we
Parallel 18: Basic Hepatobiliary Neoplasia
Authors: James Trotter, Juan Are- Nas, J Bynon, John Duffy, Hany Elbeshbeshy, Preston Foster, Rafik Ghobrial, John Goss, Vivek Kohli, Marlon Levy, Natalie Murray, Ken Washburn, Jeff Weinstein, Harlan Wright, Therese Bittermann, George Makar, David Goldberg, Oriana Miltiadous, Yujin Hoshida, M Fiel, Daniela Sia, Swan Thung, Andrew Harrington, Poh Tan, Hui Dong, Monica Higuera, Kate Revill, Charissa Chang, Jorge Rakela, Thomas Byrne, Myron Schwartz, Sander Florman, Josep Llovet
Journal: Hepatology (2014)

associated with transplantation of sicker patients without reducing patients lost on the waiting list prior to transplant.Continued evaluation of patient and organ outcomes are required to fully assess the impact of this change in liver allocation policy.
Changes in IgG-Fc N-glycan sialylation, galactosylation and fucosylation influence disease activity during and after pregnancy in rheumatoid arthritis
Authors: Albert Bondt, Maurice H J Selman, Johanna M W Hazes, André M Deelder, Manfred Wuhrer, Radboud J E M Dolhain
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Pregnancy is known to be a naturally occurring tolerisation in rheumatoid arthritis (RA). RA improves during pregnancy but flares after delivery.1 Recent publications suggest a role for N-glycosylation of the Fc-fragment of IgG herein.2 Previous studies mainly focused on changes in galactosylation (Gal). However, animal studies suggest a more important role for sialylation (SA) in the process of immune suppression.3 Fucosylation is also reported as an immunomodulatory feature by affecting binding to the Fcγ-receptor III via a carbohydrate-carbohydrate interaction.4 This study describes how changes in glycosylation of IgG are associated with decreased disease activity in RA during pregnancy and the flare after delivery. <h3>Materials and methods</h3> Sera were obtained before pregnancy, three times during pregnancy and three times after delivery from RA-patients (n=251) and healthy controls (n=32) participating in a prospective cohort study on RA and pregnancy (PARA study). At all timepoints the Disease Activity Score incorporating 28 joints (DAS28-3 (CRP)) was assessed and medication was recorded. The glycosylation states of tryptic Fc-glycopeptides of Protein G captured IgGs were analysed subclass specific (IgG1, 2/3 and 4) using a newly developed, fast and robust mass-spectrometric method.5 <h3>Results</h3> In patients and controls it was found that during pregnancy Gal (in patients for IgG1 from 59.8±1.1% to 65.3±1.0%; mean±SEM) and SA (in patients for IgG1 from 19.1±0.5% to 21.8±0.5) increase, while fucosylation (in patients for IgG1 from 94.1±0.4% to 93.7±0.4%) decreases. These changes were all associated with improvement of RA. The relative increase in sialylation was more pronounced than the increase in galactosylation (p&lt;0.01) on all IgG subclasses. Linear regression analysis showed that both changes in Gal as well as SA were independently associated with improvement of RA. After delivery levels of Gal and SA decrease, while fucosylation increases. This was associated with a relapse of disease activity. <h3>Conclusions and discussion</h3> Galactosylation, sialylation and fucosylation change during pregnancy and are correlated with disease activity. In contrast to animal studies the results of this study show that in humans not only sialylation, but also galactosylation might be involved in improving disease activity of RA during pregnancy. The molecular mechanism still has to be unravelled. Whether the immunomodulatory properties resulting from changes in glycosylation of IgG are due to influencing the interaction with Fcγ-receptors will be the subject of future research.
Potent T Cell Activation with Dimeric Peptide–Major Histocompatibility Complex Class II Ligand: The Role of CD4 Coreceptor
Authors: Abdel Rahim A. Hamad, Sean M. O'Herrin, Michael S. Lebowitz, Ananth Srikrishnan, Joan Bieler, Jonathan Schneck, Drew Pardoll
Journal: The Journal of Experimental Medicine (1998)

The interaction of the T cell receptor (TCR) with its cognate peptide–major histocompatibility complex (MHC) on the surface of antigen presenting cells (APCs) is a primary event during T cell activation. Here we used a dimeric IEk-MCC molecule to study its capacity to activate antigen-specific T cells and to directly analyze the role of CD4 in physically stabilizing the TCR–MHC interaction. Dimeric IEk-MCC stably binds to specific T cells. In addition, immobilized dimeric IEk-MCC can induce TCR downregulation and activate antigen-specific T cells more efficiently than anti-CD3. The potency of the dimeric IEk-MCC is significantly enhanced in the presence of CD4. However, CD4 does not play any significant role in stabilizing peptide-MHC–TCR interactions as it fails to enhance binding of IEk-MCC to specific T cells or influence peptide-MHC–TCR dissociation rate or TCR downregulation. Moreover, these results indicate that dimerization of peptide-MHC class II using an IgG molecular scaffold significantly increases its binding avidity leading to an enhancement of its stimulatory capacity while maintaining the physiological properties of cognate peptide–MHC complex. These peptide-MHC–IgG chimeras may, therefore, provide a novel approach to modulate antigen-specific T cell responses both in vitro and in vivo.
Mutations in Two Short Noncoding Mononucleotide Repeats in Most Microsatellite-Unstable Colorectal Cancers
Authors: Tuija Hienonen, Heli Sammalkorpi, Susa Enholm, Pia Alhopuro, Thomas D. Barber, Rainer Lehtonen, Nina N. Nupponen, Heli Lehtonen, Reijo Salovaara, Jukka-Pekka Mecklin, Heikki Järvinen, Riitta Koistinen, Diego Arango, Virpi Launonen, Bert Vogelstein, Auli Karhu, Lauri A. Aaltonen
Journal: Cancer Research (2005)

DNA mismatch repair (MMR)-deficient cells typically accumulate mutations in short repetitive DNA tracts. This microsatellite instability (MSI) facilitates malignant transformation when affecting genes with growth-related and caretaker functions. To date, several putative MSI target genes have been proposed mainly based on high mutation frequency within their coding regions. However, some intronic repeat mutations have also been suggested to associate with MSI tumorigenesis, indicating the need for additional analyses on noncoding repeats. Here we have analyzed an intronic T9 repeat of semenogelin I (SEMG1) and report mutation frequencies of 51% (75 of 146) and 62% (8 of 13) in MMR-deficient primary colorectal cancers and cell lines, respectively. The putative effect of the SEMG1 mutations was assessed by RNA and protein level analyses, but no differences were detected between colorectal cancer cell lines with different SEMG1 status. Subsequently, the general background mutation frequency of MSI colorectal cancers was assessed by screening for intergenic T9 repeat alterations. One of 10 examined repeats was mutated in 70% (102 of 145) of the colorectal cancers evaluated. The frequencies observed here are notably higher than previously published in noncoding repeats shorter than 10 bp in MMR-deficient primary tumors. Our results indicate that high mutation frequencies, similar or higher than those observed in proposed and approved target genes, can be detected in repeat tracts of MSI tumors without any apparent selection pressure. These data call for urgent and thorough large-scale evaluation of mutation frequencies in neutral short repetitive sequences in MMR-deficient tumors.
Correction of misinterpretations and misrepresentations of the female athlete triad
Authors: M J De Souza, J Alleyne, J D Vescovi, N I Williams, J L VanHeest, M P Warren
Journal: British Journal of Sports Medicine (2006)

papers that followed on the same topic, and therefore we comment only on what we read.Language is extremely important in communicating scientific findings to peers and, more importantly, to the public.Thus, it is important to be as precise as possible.The public, in turn, must weigh a given risk against other risks they are willing to assume on a daily basis (eg, driving a car, smoking cigarettes, eating French fries or not exercising), and this ''risk mix'' ultimately will influence individual risk perception and behaviour.It is our opinion that in many instances concerning the female athlete triad, the data do not match the sensational language often used to warn young girls and women of ''the risks associated with exercise''.Further, although the social marketing value of the catchphrase ''female athlete triad'' is high, it connotes something bigger than what can actually be measured properly, and, frankly, is insulting to most women athletes who train and compete hard, bear children, and continue towards a healthy and successful older age.Indeed, if undernutrition (ie, low energy availability) in sports is the primary issue at hand, then any position stand and subsequent papers to this effect should be titled as such, and should be directed towards health consequences for male and female athletes.Finally, a position stand from the American College of Sports Medicine or any other organisation attempting to influence practice and policy should be evidence based and should rely on the highest quality data and not primarily on those generated from consensus or from the same group of researchers.We remain grateful for the opportunities to state our opposing views on the female athlete triad.Such opportunities have allowed us to confront several difficult issues that are sociopolitical as well as scientific.As scientists, we should (with respect) agree to disagree on the specific areas of contention concerning the triad and trust that individuals will make informed choices about their own behaviour based on the best available knowledge.
Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA
Authors: E.L. SPEIGHT, P.M. FARR
Journal: British Journal of Dermatology (1994)

Journal Article Erythemal and therapeutic response of psoriasis to PUVA using high‐dose UVA Get access E.L. SPEIGHT, E.L. SPEIGHT Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.M. FARR P.M. FARR Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 5, 1 November 1994, Pages 667–672, https://doi.org/10.1111/j.1365-2133.1994.tb04980.x Published: 01 November 1994 Article history Accepted: 29 March 1994 Published: 01 November 1994
Factors Associated With the Onset and Persistence of Post–Lumbar Puncture Headache
Authors: Andrés E. Monserrate, Davis C. Ryman, Shengmei Ma, Chengjie Xiong, James M. Noble, John M. Ringman, John C. Morris, Adrian Danek, Felix Müller-Sarnowski, David B. Clifford, Eric M. McDade, William S. Brooks, David G. Darby, Colin L. Masters, Philip S. J. Weston, Martin R. Farlow, Neill R. Graff-Radford, Stephen P. Salloway, Anne M. Fagan, Angela Oliver, Randall J. Bateman
Journal: JAMA Neurology (2015)

This study assesses factors associated with the most common adverse event following lumbar puncture.To identify factors associated with the risk, onset, and persistence of post-dural puncture headache (PDPH).We performed univariate and multivariable analyses of 338 lumbar punctures in the Dominantly Inherited Alzheimer Network observational study using linear mixed models, adjusting for participant-level and family-level random effects.We directly evaluated associations of 3 post-lumbar puncture outcomes (immediate postprocedural headache, PDPH at 24-hour follow-up, and PDPH receiving a therapeutic blood patch) with participant age and sex, positioning, collection method, needle size, needle insertion site, and cerebrospinal fluid (CSF) volume collected.The incidence of adverse events included 73 immediate postprocedural headaches (21.6%), 59 PDPHs at 24-hour follow-up (17.5%), and 15 PDPHs receiving a therapeutic blood patch (4.4%). Greater volume of CSF collected was associated with increased risk of immediate postprocedural headache, largely owing to a nonlinear increase in risk on collection of volumes above 30 mL (odds ratio, 3.73 for >30 mL and 0.98 for <17 mL). In contrast, collection of higher volumes showed a protective effect in decreasing rates of PDPH at 24-hour follow-up and rates of PDPH receiving a therapeutic blood patch (odds ratio, 0.35 per 10 mL). Although differences in needle size did not reach statistical significance, no participant in the 24G needle group received a therapeutic blood patch compared to 8 of 253 for the larger 22G needles.Factors that acutely lower CSF pressure (eg, seated positioning or extracting very high volumes of CSF) may be associated with transient post-lumbar puncture headache, without increasing rates of persistent PDPH or therapeutic blood patch. Collection of up to 30 mL of CSF appears to be well tolerated and safe.
Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma
Authors: Esther P. M. Tjin, Richard W. J. Groen, Irma Vogelzang, Patrick W. B. Derksen, Melanie D. Klok, Helen P. Meijer, Susanne van Eeden, Steven T. Pals, Marcel Spaargaren
Journal: Blood (2005)
Viral Load Assessments of Rhinovirus (RV) by Quantitative RT-PCR in Nasal Washes from Children Treated in the Emergency Department (ED) for Asthma
Authors: V MCMEEN, M SHAKER, J GERN, H CARPER, D MURPHY, R VRTIS, T PLATTSMILLS, P HEYMANN
Journal: Journal of Allergy and Clinical Immunology (2008)