tbuckley/cabot-search huggingface dataset:
Epithelial-Cell Renewal in Cultured Duodenal Biopsies in Celiac Sprue
Authors: Jerry S. Trier, Thomas H. Browning
Journal: New England Journal of Medicine (1970)

Proliferation and migration of duodenal epithelium was studied in cultured mucosal biopsies from three normal volunteers and from three patients with celiac sprue before and after treatment with a gluten-free diet. The number of epithelial cells incorporating thymidine-3H into nuclei from the culture medium was over twice as great in pretreatment celiac-sprue biopsies as in normal biopsies. This indicates enhanced proliferation in celiac sprue. Labeled cells migrated to the surface epithelium in 24-hour cultures from all untreated patients whereas labeled cells did not migrate beyond the lower third of the villi in the normal volunteers. Surface epithelial cells, which appear damaged in uncultured celiac-sprue biopsies, reverted toward normal after only 24 hours of culture in a gluten-free environment. After six to 15 weeks of gluten withdrawal, cell proliferation and migration in cultured celiac-sprue biopsies were intermediate between pretreatment and normal biopsies. Thus, short-term treatment induces partial reversion of the abnormal epithelial-cell proliferation that characterizes untreated celiac sprue.
479. Targeted Entry of Retroviral Vectors Depends on Characteristics of the Target Receptor and the Chimeric Envelope Protein
Authors: LorraineM. Albritton, Fang Li, Pankaj Kumar, Langzhu Tan
Journal: Molecular Therapy (2005)

We present a new design for viral envelope proteins that give targeted entry of vectors. In these chimeras, the peptide ligand sequences replace the envelope glycoprotein sequences that bind the natural virus receptor. Prototype chimeras based on this design concept give transduction as high as 4 |[times]| 10 e4 transducing units per ml in a single exposure of unconcentrated virus to human cells expressing the target receptors. The transduction was specific to target receptors since synthetic peptide ligand competed for infection in a dose-dependent manner. In addition, the ability to infect murine NIH 3T3 cells expressing the natural retrovirus receptor was abolished, indicating redirection of viral entry. Thus, infection mediated by this chimeric envelope glycoproteins represents an engineered change in the host range of pseudotype virus vectors.
Abstract P1-10-01: Curcumin suppresses MMP-9 expression via inhibition of PKCα/MAPKs and NF-κB/AP-1 activation in MCF-7 cells
Authors: SK Kim, YW Kim, HJ Youn, SH Jung
Journal: Cancer Research (2012)

Abstract Background: Curcumin is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. It was recently reported for its anticancer effect on several types of cancer cells in vitro, however the molecular mechanisms of this anticancer effect are not fully understood. In the present study, we investigated the effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced matrix metalloproteinase-9(MMP-9) expression and cell invasion in MCF-7 breast cancer cells. Materials and Methods: The effect of curcumin on MCF-7 cell viability was determined using MTT assay. The cells invasion was demonstrated by the Matrigel-coated transwell assay. Western blot analysis was performed to detect the effect of curcumin on the expression of MMP-9. MMP-9 mRNA levels were analyzed by real-time PCR. NF-κB and AP-1 DNA binding was analyzed by EMSA. Results: Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and also inhibited TPA-induced translocation of PKCa from the cytosol to the membrane, but did not affect the translocation of PKCδ. Conclusion: It is concluded that curcumin inhibits the TPA-induced MMP-9 expression and cell invasion through the suppression of the PKCα/MAPK/NF-kB/AP-1 pathway in MCF-7 breast cancer cells. Accordingly, curcumin may have the therapeutic potential in restricting breast cancer metastasis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-10-01.
Comparison of two interferon- release assays and tuberculin skin test for detecting latent tuberculosis in patients with immune-mediated inflammatory diseases
Authors: S. Kleinert, O. Kurzai, J. Elias, K. Marten, C. Engelke, M. Feuchtenberger, J. Sandstede, M. Frosch, H.-P. Tony, C. Kneitz
Journal: Annals of the Rheumatic Diseases (2010)

Biological agents interfering with proinflammatory tumour necrosis factor α (TNFα) signalling have become an established tool in the treatment of rheumatoid arthritis and other chronic inflammatory conditions. Their use is associated with an increased risk for some infections including the reactivation of latent tuberculosis infection (LTBI).1 Consequently, screening for LTBI prior to onset of anti-TNFα therapy is recommended. Interferon γ release assays (IGRAs) are novel diagnostic tools for the diagnosis of LTBI and show a high specificity compared with the tuberculin skin test (TST).2 However, optimal screening procedures are still a matter of debate.1 Furthermore, questions remain with regard to the performance of IGRAs in patients receiving immunosuppressive therapy and the comparative performance of the two commercially available IGRAs.2 To address these questions, 90 successive patients from the outpatient department of rheumatology (representing an LTBI low prevalence patient group) at the University Hospital of Wurzburg, Germany were prospectively screened for LTBI using TST, TSPOT.TB (TSPOT; Oxford Immunotec, Abingdon, Oxfordshire, UK) and Quantiferon Gold (QFT; Cellestis Europe, Darmstadt, Germany) before initiation of anti-TNF treatment). Underlying disease entities included ankylosing spondylitis (n=18 patients), rheumatoid arthritis (n=51), psoriatic arthritis (n=10) and other autoimmune diseases (n=11). Nineteen patients were receiving a steroid regimen of ≥7.5 mg prednisone equivalent and …
Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial
Authors: Emily L Webb, Patrice A Mawa, Juliet Ndibazza, Dennison Kizito, Alice Namatovu, Jacqueline Kyosiimire-Lugemwa, Bridget Nanteza, Margaret Nampijja, Lawrence Muhangi, Patrick W Woodburn, Hellen Akurut, Harriet Mpairwe, Miriam Akello, Nancy Lyadda, Joseph Bukusuba, Macklyn Kihembo, Moses Kizza, Robert Kizindo, Juliet Nabulime, Christine Ameke, Proscovia B Namujju, Robert Tweyongyere, Moses Muwanga, James AG Whitworth, Alison M Elliott
Journal: The Lancet (2010)
Assessing Generalizability of the Findings of Sigmoidoscopy Screening Trials: The Case of SCORE Trial
Authors: Carlo Senore, Luigina Bonelli, Stefania Sciallero, Claudia Casella, Alessandra Santarelli, Paola Armaroli, Roberto Zanetti, Nereo Segnan
Journal: JNCI Journal of the National Cancer Institute (2014)

Several reports indicated that volunteers enrolled in preventive trials tend to show a different profile, with respect to sociodemographic characteristics, health-related behaviors, or medical history, compared with the source population. We conducted an incidence and mortality follow-up within a cohort of subjects who had been mailed a recruitment questionnaire in the SCORE trial of sigmoidoscopy (FS) screening for colorectal cancer (CRC) to assess the impact of self-selection in the study of volunteers willing to be screened on the outcomes estimates and on the generalizability of the results. We compared baseline demographics, CRC risk, and overall mortality at 11-year follow-up of responders declaring their interest in screening, with those of nonresponders and of responders not interested in screening using logistic regression and Cox proportional hazards multivariable models. Both subjects who volunteered in the trial and those who refused were better educated than nonresponders. Men and people younger than age 60 years were more likely to volunteer among responders. At 11-year follow-up, interested responders showed a similar CRC risk as nonresponders, while CRC mortality was substantially reduced (hazard ratio [HR] = 0.70, 95% confidence interval [CI] = 0.54 to 0.91). All-cause mortality was reduced both among interested (HR = 0.61, 95% CI = 0.57 to 0.65) and uninterested responders (HR = 0.81, 95% CI = 0.76 to 0.86). The implementation of an FS population–based screening program would result in a similar reduction in CRC incidence, as observed in the SCORE trial, and likely in a larger impact on CRC mortality.
Requirement for Casper (c-FLIP) in Regulation of Death Receptor–Induced Apoptosis and Embryonic Development
Authors: Wen-Chen Yeh, Annick Itie, Andrew J Elia, Michelle Ng, Hong-Bing Shu, Andrew Wakeham, Christine Mirtsos, Nobutaka Suzuki, Madeleine Bonnard, David V Goeddel, Tak W Mak
Journal: Immunity (2000)
Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in rats
Authors: Xiaocong Chen, Becky M. Sebastian, Hui Tang, Megan M. McMullen, Armend Axhemi, Donald W. Jacobsen, Laura E. Nagy
Journal: Hepatology (2008)

Chronic ethanol feeding decreases expression of adiponectin by adipocytes and circulating adiponectin. Adiponectin treatment during chronic ethanol feeding prevents liver injury in mice. Chronic ethanol feeding also increases oxidative and endoplasmic reticulum (ER) stress in adipose tissue. Here we tested the hypothesis that supplemental taurine, an amino acid that functions as a chemical chaperone/osmolyte and enhances cellular antioxidant activity, would prevent ethanol-induced decreases in adiponectin expression and attenuate liver injury. Serum adiponectin concentrations decreased as early as 4 to 7 days after feeding rats a 36% ethanol diet. This rapid decrease was associated with increased oxidative, but not ER, stress in subcutaneous adipose tissue. Taurine prevented ethanol-induced oxidative stress and increased inflammatory cytokine expression in adipose tissue. Ethanol feeding also rapidly decreased expression of transcription factors regulating adiponectin expression (CCAAT/enhancer binding protein alpha; peroxisome proliferator-activated receptor alpha/gamma) in subcutaneous adipose tissue. Taurine prevented the ethanol-induced decrease in CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor alpha, normalizing adiponectin messenger (m)RNA and serum adiponectin concentrations. In the liver, taurine prevented ethanol-induced oxidative stress and attenuated tumor necrosis factor alpha expression and steatosis, at least in part, by increasing expression of genes involved in fatty acid oxidation.In subcutaneous adipose tissue, taurine decreased ethanol-induced oxidative stress and cytokine expression, as well as normalized expression of adiponectin mRNA. Taurine prevented ethanol-induced decreases in serum adiponectin; normalized adiponectin was associated with a reduction in hepatic oxidative stress, tumor necrosis factor alpha expression, and steatosis. Taken together, these data demonstrate that taurine has important protective effects against ethanol-induced tissue injury in both adipose and liver tissue.
Standardized Reporting of Clinical Practice Guidelines: A Proposal from the Conference on Guideline Standardization
Authors: Richard N. Shiffman, Paul Shekelle, J Marc Overhage, Jean Slutsky, Jeremy Grimshaw, Aniruddha M. Deshpande
Journal: Annals of Internal Medicine (2003)

Despite enormous energies invested in authoring clinical practice guidelines, the quality of individual guidelines varies considerably. The Conference on Guideline Standardization (COGS) was convened in April 2002 to define a standard for guideline reporting that would promote guideline quality and facilitate implementation. Twenty-three people with expertise and experience in guideline development, dissemination, and implementation participated. A list of candidate guideline components was assembled from the Institute of Medicine Provisional Instrument for Assessing Clinical Guidelines, the National Guideline Clearinghouse, the Guideline Elements Model, and other published guideline models. In a 2-stage modified Delphi process, panelists first rated their agreement with the statement that [Item name] is a necessary component of practice guidelines on a 9-point scale. An individualized report was prepared for each panelist; the report summarized the panelist's rating for each item and the median and dispersion of rankings of all the panelists. In a second round, panelists separately rated necessity for validity and necessity for practical application. Items achieving a median rank of 7 or higher on either scale, with low disagreement index, were retained as necessary guideline components. Representatives of 22 organizations active in guideline development reviewed the proposed items and commented favorably. Closely related items were consolidated into 18 topics to create the COGS checklist. This checklist provides a framework to support more comprehensive documentation of practice guidelines. Most organizations that are active in guideline development found the component items to be comprehensive and to fit within their existing development methods. *For a list of participants in the COGS, see the Appendix.
Developmental aspects of the renal responses to hemorrhage during converting-enzyme inhibition in fetal lambs.
Authors: R A Gomez, J E Robillard
Journal: Circulation Research (1984)

The role of the renin-angiotensin system in modulating the renal hemodynamic and functional responses to reductions of fetoplacental blood volume (8.8-35.5%) was studied in two groups of fetal lambs (less than 120 days and greater than 130 days gestation; term 145 days) during infusion of either captopril (experimental fetuses) or dextrose 5% in water (control fetuses). At high hemorrhage levels (level III), renal blood flow decreased and renal vascular resistance increased significantly in both groups of fetuses (less than 120 days and greater than 130 days), either treated or not treated with captopril. However, at low hemorrhage levels (levels I and II), and contrary to what was observed in young fetuses (less than 120 days), near-term fetuses (greater than 130 days) receiving captopril showed neither significant decreases in renal blood flow nor increases in renal vascular resistance, whereas untreated fetuses of the same gestational ages demonstrated significant decreases in renal blood flow and increases in renal vascular resistance. It was found in both less than 120 day and greater than 130 day fetuses that hemorrhage is associated with a decrease in urinary flow rate and free water clearance accompanied by an increase in urine osmolality and sodium reabsorption. It was shown that captopril does not modify this response. The present study also demonstrated that the blood pressure response to hemorrhage was characterized by a similar decrease in less than 120 day fetuses, whether treated or untreated with captopril. On the other hand, blood pressure did not change in control fetuses greater than 130 days, but decreased slightly in captopril-treated fetuses during hemorrhage. Taken together, the present results tend to suggest that the renin-angiotensin system may be an important modulator of the renal hemodynamic response to low level hemorrhage as fetuses approach term, and may be more important in controlling blood pressure in near-term than in young fetuses.
DIVERGING EFFECTS OF SILDENAFIL ON VENTRICULAR-VASCULAR FUNCTION IN HFPEF
Authors: Barry Borlaug, Gregory Lewis, Steven McNulty, Marc Semigran, Martin LeWinter, Horng Chen, Grace Lin, Kevin Anstrom, Eric Velazquez, Monica Shah, Kenneth Margulies, Margaret Redfield
Journal: Journal of the American College of Cardiology (2014)
GP referrals to hospital increased 6% last year but budget rose only 2-3%, King's Fund hears
Authors: N. Hawkes
Journal: BMJ (2014)

<h3>Background</h3> An intriguing phenomenon in many solid tumors is the de novo lymphoid neogenesis of tertiary lymphoid structure (TLS). However, it remains unclear whether spontaneous TLS restricts or promotes tumor progression. MDSCs are major contributors to tumor evasion of adaptive immune responses. We hypothesize that MDSCs repel TLS as a histological pattern in bladder cancers. <h3>Methods</h3> To perform a spatial analysis of MDSDs and other immune cell phenotypes in the bladder tumor microenvironment we used MultiOmyx™, an immunofluorescence (IF) assay utilizing a pair of directly conjugated Cyanine dye-labeled (Cy3, Cy5) antibodies per round of staining. Using a 14-marker panel and proprietary cell segmentation and classification algorithms developed at NeoGenomics we have analyzed the presence of TLS (positive for CD20, CD3, and PNAd), followed by a spatial analysis of MDSCs, T cell subtypes, and M1/M2-type tumor-associated macrophages (TAMs) in relation to the TLS in 25 FFPE samples from patients with bladder cancer. <h3>Results</h3> To test our initial hypothesis that MDSCs repel TLS in bladder cancer, we quantitated the presence of immune cell phenotypes inside the TLS, and in tissue regions near and far from the TLS. As expected we found a significantly higher density of B cells and T cells present inside the TLS compared to either near or far from the TLS. However, when quantitating MDSCs we found a linear decrease related to their proximity to the TLS, with a 25% lower density in the region near the TLS, and a 46% decrease in the regions far from the TLS. This pattern was not observed for TAMs that were found at the same density inside, near, or far from the TLS, confirming that this pattern is MDSC specific. We are currently performing further analysis of MDSCs co-expressed with either CXCR2 or iNOS for additional answers to the possible mechanisms behind this finding. <h3>Conclusions</h3> The finding on the co-abundance of MDSCs and T/B cells following the distance from TLS suggests that MDSCs may repel TLS-derived T and B cells through cell-cell interaction via physical proximity. This study has important implications for bladder cancer immunotherapy.
Collecting data on female genital mutilation
Authors: K. Erskine
Journal: BMJ (2014)

UK government’s actions still characterised by a failure to think things through 

Female genital mutilation is defined by the World Health Organization as “all procedures that involve partial or total removal of the external female genitalia or other injury to the female genitalia for non-medical reasons.” A horrendous form of child abuse, in its most extreme form (type 3) it involves removing the clitoris and labia and narrowing the vaginal introitus. More than 100 million women worldwide are affected.

The procedure has many complications including dyspareunia, sepsis, and death—procedure related mortality was estimated at 2.3% in one country.1 It is done for many reasons—there is no single religious basis. In some cultures a woman who has not undergone the procedure may be thought unmarriageable. In women with type 3 mutilation, the introitus may be too narrow for childbirth, and the tissues that have sealed together need to be separated; this is termed deinfibulation. Female genital mutilation was made an offence in 1985 in the United Kingdom, with a penalty of up to 14 years in prison.

A government declaration to end the practice …
Abstract B15: Bone marrow stromal cell-secreted inflammatory cytokines promote treatment resistance and survival of prostate cancer cells
Authors: Megan Chang, Micaela Morgado, Viral Patel, Michael Gwede, Mary Cindy Farach-Carson, Nikki Delk
Journal: Cancer Research (2015)

Abstract It is well established that prostate cancer (PCa) cells hone to, adapt, and thrive in the bone. Importantly, bone metastases are found in over 80% of PCa deaths. Therefore, it is imperative to elucidate and characterize the molecular mechanisms that enable PCa cells to thrive in the bone and resist conventional PCa therapies, such as hormone ablation or anti-androgens. We found that the HS-5 bone marrow stromal cell (BMSC) line, a secretory BMSC line that can support hematopoietic stem cell growth, secretes paracrine factors that induce apoptosis in PCa cells. However a subpopulation of the PCa cells can survive the BMSC-induced death. The surviving PCa subpopulation differentiates into a neuronal morphology and looses androgen receptor (AR) expression, reminiscent of treatment-resistant neuroendocrine PCa. Ideally, the loss of AR would induce PCa cell death; however we observe a concomitant increase in the autophagy-related cell survival protein, p62/SQSTM1, and induction of cytoprotective autophagy. Furthermore, we find that interleukin-1 beta (IL-1β) and IL-6, inflammatory cytokine secreted by HS-5 BMSCs, are sufficient to promote PCa neuronal morphology, reduce AR accumulation, upregulate p62/SQSTM1 levels, and induce autophagy. In addition, genetic silencing of p62/SQSTM1 causes PCa cell death and pharmacological inhibition of cytokine or autophagy signaling attenuates PCa neuroendocrine differentiation. Thus, our PCa-bone marrow stromal cell model suggests that PCa cells can co-opt the immune system in the bone microenvironment leading to PCa androgen independence, treatment resistance, and survival in the bone. Furthermore, our data suggests that inhibiting inflammatory cytokine signaling and/or the autophagy process are rational strategies to combat PCa bone metastasis. Citation Format: Megan Chang, Micaela Morgado, Viral Patel, Michael Gwede, Mary Cindy Farach-Carson, Nikki Delk. Bone marrow stromal cell-secreted inflammatory cytokines promote treatment resistance and survival of prostate cancer cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B15. doi:10.1158/1538-7445.CHTME14-B15
“A Non-Editorial on Non-Hypoglycemia”
Authors: Cahill Gf, Soeldner Js
Journal: New England Journal of Medicine (1974)

From the point of view of energy, the human brain in the adult of average size squanders about one fifth of the body's basal caloric output, consuming oxygen and glucose and producing water, carbon dioxide and heat. Under the usual circumstances, only glucose is employed as fuel. The chemical or electric energy leaving the brain via the exiting nerves and spinal cord is infinitesimal compared to that leaving as heat added to the venous outflow. Although this summary describes brain as a wasteful intracranial radiator, the heat is mainly a by-product of the energetics needed to maintain electrochemical gradients as . . .