tbuckley/cabot-search huggingface dataset:
Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis
Authors: Smriti Agrawal, Per Anderson, Madeleine Durbeej, Nico van Rooijen, Fredrik Ivars, Ghislain Opdenakker, Lydia M. Sorokin
Journal: The Journal of Experimental Medicine (2006)

The endothelial cell monolayer of cerebral vessels and its basement membrane (BM) are ensheathed by the astrocyte endfeet, the leptomeningeal cells, and their associated parenchymal BM, all of which contribute to establishment of the blood–brain barrier (BBB). As a consequence of this unique structure, leukocyte penetration of cerebral vessels is a multistep event. In mouse experimental autoimmune encephalomyelitis (EAE), a widely used central nervous system inflammatory model, leukocytes first penetrate the endothelial cell monolayer and underlying BM using integrin β1-mediated processes, but mechanisms used to penetrate the second barrier defined by the parenchymal BM and glia limitans remain uninvestigated. We show here that macrophage-derived gelatinase (matrix metalloproteinase [MMP]-2 and MMP-9) activity is crucial for leukocyte penetration of the parenchymal BM. Dystroglycan, a transmembrane receptor that anchors astrocyte endfeet to the parenchymal BM via high affinity interactions with laminins 1 and 2, perlecan and agrin, is identified as a specific substrate of MMP-2 and MMP-9. Ablation of both MMP-2 and MMP-9 in double knockout mice confers resistance to EAE by inhibiting dystroglycan cleavage and preventing leukocyte infiltration. This is the first description of selective in situ proteolytic damage of a BBB-specific molecule at sites of leukocyte infiltration.
Proteomic Analysis of Bovine Nucleolus
Authors: Amrutlal K. Patel, Doug Olson, Suresh K. Tikoo
Journal: Genomics Proteomics & Bioinformatics (2010)

Nucleolus is the most prominent subnuclear structure, which performs a wide variety of functions in the eukaryotic cellular processes. In order to understand the structural and functional role of the nucleoli in bovine cells, we analyzed the proteomic composition of the bovine nucleoli. The nucleoli were isolated from Madin Darby bovine kidney cells and subjected to proteomic analysis by LC-MS/MS after fractionation by SDS-PAGE and strong cation exchange chromatography. Analysis of the data using the Mascot database search and the GPM database search identified 311 proteins in the bovine nucleoli, which contained 22 proteins previously not identified in the proteomic analysis of human nucleoli. Analysis of the identified proteins using the GoMiner software suggested that the bovine nucleoli contained proteins involved in ribosomal biogenesis, cell cycle control, transcriptional, translational and post-translational regulation, transport, and structural organization.
Calcium, Vitamin D, Dairy Products, and Mortality Among Colorectal Cancer Survivors: The Cancer Prevention Study-II Nutrition Cohort
Authors: Baiyu Yang, Marjorie L. McCullough, Susan M. Gapstur, Eric J. Jacobs, Roberd M. Bostick, Veronika Fedirko, W. Dana Flanders, Peter T. Campbell
Journal: Journal of Clinical Oncology (2014)

Purpose Higher calcium, vitamin D, and dairy product intakes are associated with lower colorectal cancer incidence, but their impacts on colorectal cancer survival are unclear. We evaluated associations of calcium, vitamin D, and dairy product intakes before and after colorectal cancer diagnosis with all-cause and colorectal cancer-specific mortality among colorectal cancer patients. Patients and Methods This analysis included 2,284 participants in a prospective cohort who were diagnosed with invasive, nonmetastatic colorectal cancer after baseline (1992 or 1993) and up to 2009. Mortality follow-up was through 2010. Prediagnosis risk factor information was collected on the baseline questionnaire. Postdiagnosis information was collected via questionnaires in 1999 and 2003 and was available for 1,111 patients. Results A total of 949 participants with colorectal cancer died during follow-up, including 408 from colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, postdiagnosis total calcium intake was inversely associated with all-cause mortality (relative risk [RR] for those in the highest relative to the lowest quartiles, 0.72; 95% CI, 0.53-0.98; P trend = .02) and associated with marginally statistically significant reduced colorectal cancer-specific mortality (RR, 0.59; 95% CI, 0.33 to 1.05; P trend = .01). An inverse association with all-cause mortality was also observed for postdiagnosis milk intake (RR, 0.72; 95% CI, 0.55 to 0.94; P trend = .02), but not vitamin D intake. Prediagnosis calcium, vitamin D, and dairy product intakes were not associated with any mortality outcomes. Conclusion Higher postdiagnosis intakes of total calcium and milk may be associated with lower risk of death among patients with nonmetastatic colorectal cancer.
Impact of an Intensive Lifestyle Intervention on Use and Cost of Medical Services Among Overweight and Obese Adults With Type 2 Diabetes: The Action for Health in Diabetes
Authors: Mark A. Espeland, Henry A. Glick, Alain Bertoni, Frederick L. Brancati, George A. Bray, Jeanne M. Clark, Jeffrey M. Curtis, Caitlin Egan, Mary Evans, John P. Foreyt, Siran Ghazarian, Edward W. Gregg, Helen P. Hazuda, James O. Hill, Don Hire, Edward S. Horton, Van S. Hubbard, John M. Jakicic, Robert W. Jeffery, Karen C. Johnson, Steven E. Kahn, Tina Killean, Abbas E. Kitabchi, William C. Knowler, Andrea Kriska, Cora E. Lewis, Marsha Miller, Maria G. Montez, Anne Murillo, David M. Nathan, Ebenezer Nyenwe, Jennifer Patricio, Anne L. Peters, Xavier Pi-Sunyer, Henry Pownall, J. Bruce Redmon, Julia Rushing, Donna H. Ryan, Monika Safford, Adam G. Tsai, Thomas A. Wadden, Rena R. Wing, Susan Z. Yanovski, Ping Zhang
Journal: Diabetes Care (2014)

To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial.A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years.ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385-7,175); however, these were not evident among individuals with a history of cardiovascular disease.Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs.
Renal insufficiency after intravenous immune globulin therapy
Authors: A V Cayco, M A Perazella, J P Hayslett
Journal: Journal of the American Society of Nephrology (1997)

Over the past decade, intravenous immune globulin therapy (IVIG) has gained widespread use for a variety of clinical disorders. IVIG treatment is associated with a number of complications, including acute renal failure (ARF). Although the cause of IVIG-associated ARF is unknown, it may be related to the stabilizing agent used in the IVIG preparation. The development and resolution of ARF is typically rapid, but is some cases recovery may be delayed and require renal replacement therapy. In such patients, recurrence of ARF may be avoided by selection of a preparation with a different stabilizing agent. Two cases of IVIG-induced ARF are described, and all reported cases are analyzed to assess the probable mechanism of renal injury.
Conditional Loss of Uterine <i>Pten</i> Unfailingly and Rapidly Induces Endometrial Cancer in Mice
Authors: Takiko Daikoku, Yasushi Hirota, Susanne Tranguch, Ayesha R. Joshi, Francesco J. DeMayo, John P. Lydon, Lora H. Ellenson, Sudhansu K. Dey
Journal: Cancer Research (2008)

Abstract Etiology of endometrial cancer (EMC) is not fully understood. Animal models with rapidly and spontaneously developing EMC will help explore mechanisms of cancer initiation and progression. Pten+/− mice are currently being used as a model to study EMC. These females develop atypical endometrial hyperplasia of which ∼20% progresses to EMC. In addition, tumors develop in other organs, complicating the use of this model to specifically study EMC. Here, we show that conditional deletion of endometrial Pten results in EMC in all female mice as early as age 1 month with myometrial invasion occurring by 3 months. In contrast, conditional deletion of endometrial p53 had no phenotype within this time frame. Whereas mice with endometrial Pten deletion had a life span of ∼5 months, mice with combined deletion of endometrial Pten and p53 had a shorter life span with an exacerbated disease state. Such rapid development of EMC from homozygous loss of endometrial Pten suggests that this organ is very sensitive to this tumor suppressor gene for tumor development. All lesions at early stages exhibited elevated Cox-2 and phospho-Akt levels, hallmarks of solid tumors. More interestingly, levels of two microRNAs miR-199a* and miR-101a that posttranscriptionally inhibit Cox-2 expression were down-regulated in tumors in parallel with Cox-2 up-regulation. This mouse model in which the loxP-Cre system has been used to delete endometrial Pten and/or p53 allows us to study in detail the initiation and progression of EMC. These mouse models have the added advantage because they mimic several features of human EMC. [Cancer Res 2008;68(14):5619–27]
Who Are the Long-QT Syndrome Patients Who Receive an Implantable Cardioverter-Defibrillator and What Happens to Them?
Authors: Peter J. Schwartz, Carla Spazzolini, Silvia G. Priori, Lia Crotti, Alessandro Vicentini, Maurizio Landolina, Maurizio Gasparini, Arthur A.M. Wilde, Reinoud E. Knops, Isabelle Denjoy, Lauri Toivonen, Gerold Mönnig, Majid Al-Fayyadh, Luc Jordaens, Martin Borggrefe, Christina Holmgren, Pedro Brugada, Luc De Roy, Stefan H. Hohnloser, Paul A. Brink
Journal: Circulation (2010)

A rapidly growing number of long-QT syndrome (LQTS) patients are being treated with an implantable cardioverter-defibrillator (ICD). ICDs may pose problems, especially in the young. We sought to determine the characteristics of the LQTS patients receiving an ICD, the indications, and the aftermath.The study population included 233 patients. Beginning in 2002, data were collected prospectively. Female patients (77%) and LQT3 patients (22% of genotype positive) were overrepresented; mean QTc was 516±65 milliseconds; mean age at implantation was 30±17 years; and genotype was known in 59% of patients. Unexpectedly, 9% of patients were asymptomatic before implantation. Asymptomatic patients, almost absent among LQT1 and LQT2 patients, represented 45% of LQT3 patients. Patients with cardiac symptoms made up 91% of all study participants, but only 44% had cardiac arrest before ICD implantation. In addition, 41% of patients received an ICD without having first been on LQTS therapy. During follow-up, 4.6±3.2 years, at least 1 appropriate shock was received by 28% of patients, and adverse events occurred in 25%. Appropriate ICD therapies were predicted by age <20 years at implantation, a QTc >500 milliseconds, prior cardiac arrest, and cardiac events despite therapy; within 7 years, appropriate shocks occurred in no patients with none of these factors and in 70% of those with all factors.Reflecting previous concepts, ICDs were implanted in some LQTS patients whose high risk now appears questionable. Refined criteria for implantation, reassessment of pros and cons, ICD reprogramming, and consideration for other existing therapeutic options are necessary.
Idiotypes Expressed Early in Experimental <i>Schistosoma mansoni</i> Infections Predict Clinical Outcomes of Chronic Disease
Authors: M. Angela Montesano, Daniel G. Colley, Margaret T. Willard, George L. Freeman, W. Evan Secor
Journal: The Journal of Experimental Medicine (2002)

In murine Schistosoma mansoni infections, schistosome-specific cross-reactive idiotypes (CRI) are present in the sera of mice with moderate splenomegaly syndrome (MSS) at 20 wk after infection. In contrast, sera from animals that have the more severe hypersplenomegaly syndrome (HSS) at 20 wk of infection do not express these CRI in their sera. To examine when these regulatory CRI first appear in mice that eventually develop MSS, sera from infected animals were monitored for CRI from 1.5 to 20 wk of infection. In mice that eventually developed MSS, CRI were detected by 5 to 6 wk after infection, plateaued by 8 to 10 wk, and persisted through 20 wk of infection. Animals that developed HSS pathology or that died before 20 wk of infection never expressed CRI. Moreover, CRI levels present in the sera of mice at 6 wk of infection were inversely correlated with splenomegaly and hepatic fibrosis, but not with parasitologic measures, at 20 wk after infection. These results suggest that critical events occur very early in some schistosome infections that induce the production of regulatory idiotypes and that the presence or absence of these idiotypes predicts, and possibly determines, subsequent morbidity.
Overexpression of MACC1 leads to downstream activation of HGF/MET and potentiates metastasis and recurrence of colorectal cancer
Authors: Lisa A Boardman
Journal: Genome Medicine (2009)

Survival rates from colorectal cancer (CRC) differ dramatically according to the stage of the tumor at diagnosis, with survival rates of 90% for patients with stage I disease but only 49% for those with stage III cancer. Many serum and tumor markers have been identified but none has provided a significant improvement over tumor stage as a prognostic indicator for cancer recurrence for patients with stage II or III disease. Aberrant activation of the hepatocyte growth factor (HGF)/HGF receptor (MET) signaling pathway is associated with both malignant transformation and metastatic potential of CRC. MACC1 (metastasis-associated in colon cancer-1) is a newly discovered gene that regulates this signaling cascade. The significant correlation between overexpression of MACC1 in CRC and both malignant transformation and subsequent risk for metastases in stage II and III CRC indicates that MACC1 tumor typing may prove valuable for determining risk for CRC recurrence. MACC1 may also be an important therapeutic target for CRC treatment.
Tolerance for self IG at the level of the Ly1+ T cell.
Authors: E K Bikoff
Journal: The Journal of Experimental Medicine (1983)

Experiments presented in this report demonstrate that specificity of the Ly1+ T cell proliferative response to NP-modified Ig is controlled by Igh-C-linked genes. In addition, we describe the mechanism whereby Igh-C-encoded molecules influence Ly1+ T cell activity. We show that Igh-C-linked control of T cell responses to NP-modified Ig is a secondary consequence of naturally acquired tolerance for self Ig. Unresponsiveness to self Ig is not due to a defect expressed functionally at the level of the antigen-presenting cell, nor is it associated with active suppression. These results suggest that tolerance for self Ig at the level of the Ly1+ T cell is due to functional deletion of Ly1+ T cell clones specific for self Ig. The possibility is considered that regulatory effects mediated by passively administered antibodies may in part be due to induction of Ly1+ T cell tolerance for self Ig.
The use of dynamic O-(2-18F-fluoroethyl)-L-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma
Authors: N. Galldiks, G. Stoffels, C. Filss, M. Rapp, T. Blau, C. Tscherpel, G. Ceccon, V. Dunkl, M. Weinzierl, M. Stoffel, M. Sabel, G. R. Fink, N. J. Shah, K.-J. Langen
Journal: Neuro-Oncology (2015)

We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma.We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test.Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak <45 min was present (sensitivity, 93%; specificity, 100%; accuracy, 93%; positive predictive value, 100%; P < .001).Static and dynamic (18)F-FET PET parameters differentiate progressive or recurrent glioma from treatment-related nonneoplastic changes with higher accuracy than conventional MRI.
Fas Ligand Delivery by a Prostate-Restricted Replicative Adenovirus Enhances Safety and Antitumor Efficacy
Authors: Xiong Li, You-Hong Liu, Yan-Ping Zhang, Shaobo Zhang, Xinzhu Pu, Thomas A. Gardner, Meei-Huey Jeng, Chinghai Kao
Journal: Clinical Cancer Research (2007)

Recent studies showed that Fas ligand (FasL) induced apoptosis in tumor cells and suppressed the immune response in several types of tumors. However, the toxicity of FasL limited further administration. This study delivered FasL in prostate cancer cells using an improved prostate-restricted replicative adenovirus (PRRA), thereby improving the antitumor effect while decreasing systemic toxicity.We designed a FasL-armed PRRA, called AdIU3, by placing adenoviral E1a and E4 genes, FasL cDNA, and E1b gene under the control of two individual PSES enhancers. Tissue-specific viral replication and FasL expression were analyzed, and the tumor killing effect of AdIU3 was investigated both in vitro and in vivo using androgen-independent CWR22rv s.c. models via local administration and bone models via systemic administration. The safety of systemic administration of AdIU3 was evaluated. AdCMVFasL, in which FasL was controlled by a universal cytomegalovirus (CMV) promoter, was used as a control.AdIU3 enhanced FasL expression in prostate-specific antigen (PSA)/prostate-specific membrane antigen (PSMA)-positive cells but not in PSA/PMSA-negative cells. It induced apoptosis and killed PSA/PMSA-positive prostate cancer cells but spared normal human fibroblasts, hepatocytes, and negative cells. The increase in killing activity was confirmed to result in part from a bystander killing effect. Furthermore, AdIU3 was more effective than a plain PRRA in inhibiting the growth of androgen-independent prostate cancer xenografts and bone tumor formation. Importantly, systemic administration of AdIU3 resulted in undetectable toxicity, whereas the same doses of AdCMVFasL killed all mice due to multiviscera failure in 16 h.AdIU3 decreased the toxicity of FasL by controlling its expression with PSES, with greatly enhanced prostate cancer antitumor efficacy. The results suggested that toxic antitumor factors can be delivered safely by a PRRA.
Continuous Intravesical Lidocaine Treatment for Interstitial Cystitis/Bladder Pain Syndrome: Safety and Efficacy of a New Drug Delivery Device
Authors: J. Curtis Nickel, Pankaj Jain, Neal Shore, Jessica Anderson, Dennis Giesing, Heejin Lee, Grace Kim, Karen Daniel, Suellen White, Cheryl Larrivee-Elkins, Julie Lekstrom-Himes, Michael Cima
Journal: Science Translational Medicine (2012)

Interstitial cystitis/bladder pain syndrome patients tolerate and experience symptomatic relief from a bladder-borne device that provides continuous lidocaine delivery.
The E-Z Reader model of eye-movement control in reading: Comparisons to other models
Authors: Erik D. Reichle, Keith Rayner, Alexander Pollatsek
Journal: Behavioral and Brain Sciences (2003)

The E-Z Reader model (Reichle et al. 1998; 1999) provides a theoretical framework for understanding how word identification, visual processing, attention, and oculomotor control jointly determine when and where the eyes move during reading. In this article, we first review what is known about eye movements during reading. Then we provide an updated version of the model (E-Z Reader 7) and describe how it accounts for basic findings about eye movement control in reading. We then review several alternative models of eye movement control in reading, discussing both their core assumptions and their theoretical scope. On the basis of this discussion, we conclude that E-Z Reader provides the most comprehensive account of eye movement control during reading. Finally, we provide a brief overview of what is known about the neural systems that support the various components of reading, and suggest how the cognitive constructs of our model might map onto this neural architecture.
Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution.
Authors: M Krotkiewski, P Björntorp, L Sjöström, U Smith
Journal: Journal of Clinical Investigation (1983)

The distribution of adipose tissue thickness, fat cell weight (FCW), and number (FCN) were studied in four regions in randomly selected middle-aged men and women and in 930 obese individuals. Both the obese and the randomly selected men were found to have the largest adipose tissue thickness in the abdominal region. Women, however, showed a relative preponderance for the gluteal and femoral regions. FCW increased with expanding body fat up to a maximal size of approximately 0.7-0.8 micrograms/cell in each region. After this increase in FCW, a more rapid increase in FCN was found. For the same degree of relative overweight, men had higher triglyceride, fasting glucose, and insulin levels; higher sums of glucose and insulin levels during an oral glucose tolerance test; and higher blood pressure. Furthermore, elevated fasting glucose levels (greater than 7.4 mM) occurred twice as often in the males. These differences between males and females persisted even after body fat matching. A male risk profile was seen in women characterized by abdominal obesity (high waist/hip circumference ratio) as compared to women with the typical peripheral obesity. Stepwise multiple regression analyses in both women and men showed the obesity complications to be associated in a first step to waist/hip circumference or body fat and in a second to abdominal fat cell size. It may thus be concluded that: (a) In both obese and nonobese subjects, regional differences exist between the sexes with regard to adipose tissue distribution. (b) Moderate expansion of body fat is mainly due to FCW enlargement, which is subsequently followed by increased FCN. (c) Men and women with a male abdominal type of obesity are more susceptible to the effect of excess body fat on lipid and carbohydrate metabolism.
Combined analysis of E-cadherin gene (CDH1) promoter hypermethylation and E-cadherin protein expression in patients with gastric cancer: implications for treatment with demethylating drugs
Authors: F. Graziano, F. Arduini, A. Ruzzo, A. Mandolesi, I. Bearzi, R. Silva, P. Muretto, E. Testa, D. Mari, M. Magnani, M. Scartozzi, S. Cascinu
Journal: Annals of Oncology (2004)