tbuckley/cabot-search huggingface dataset:
Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men.
Authors: A A Portale, B P Halloran, R C Morris
Journal: Journal of Clinical Investigation (1989)

We asked this question: in normal humans, is either a normal dietary intake or normal serum concentration of phosphorus a determinant of the serum concentration of 1,25(OH)2D? In seven normal men whose dietary phosphorus was decreased from 2,300 to 625 mg/d, each intake for 8-9 d, under strictly controlled, normal metabolic conditions, we measured serum concentrations of 1,25(OH)2D daily, and concentrations of phosphorus hourly throughout a 24-h period, before and after restriction. Decreasing dietary phosphorus induced: (a) a 58% increase in serum levels of 1,25(OH)2D; (b) a 35% decrease in serum levels of phosphorus measured in the afternoon; (c) a 12% decrease in the 24-h mean serum level of phosphorus; but, (d) no decrease in morning fasting levels of phosphorus. Serum concentrations of 1,25(OH)2D varied inversely and significantly with 24-h mean concentrations of phosphorus (r = -0.77, P less than 0.001). When these data are combined with those of our prior study in which dietary phosphorus was varied over an extreme range, the relationship between serum levels of 1,25(OH)2D and 24-h mean serum levels of phosphorus is even stronger (r = -0.90, P less than 0.001). In the aggregate, the results demonstrate that in normal men, dietary phosphorus throughout a normal range and beyond, can finely regulate the renal production and serum concentration of 1,25(OH)2D, and provide evidence that this regulation is mediated by fine modulation of the serum concentration of phosphorus.
Identification of Atherosclerotic Plaque Components With Intravascular Ultrasound Elastography In Vivo
Authors: Chris L. de Korte, Marion J. Sierevogel, Frits Mastik, Chaylendra Strijder, Johannes A. Schaar, Evelyn Velema, Gerard Pasterkamp, P.W. Serruys, Anton F.W. van der Steen
Journal: Circulation (2002)

Background — Intravascular ultrasound elastography assesses the local strain of the atherosclerotic vessel wall. In the present study, the potential to identify different plaque components in vivo was investigated. Methods and Results — Atherosclerotic external iliac and femoral arteries (n=24) of 6 Yucatan pigs were investigated. Before termination, elastographic data were acquired with a 20-MHz Visions catheter. Two frames acquired at end-diastole with a pressure differential of ≈4 mm Hg were acquired to obtain the elastograms. Before dissection, x-ray was used to identify the arterial segments that had been investigated by ultrasound. Specimens were stained for collagen, fat, and macrophages. Plaques were classified as absent, early fibrous lesion, early fatty lesion, or advanced fibrous plaque. The average strains in the plaque-free arterial wall (0.21%) and the early (0.24%) and advanced fibrous plaques (0.22%) were similar. Higher average strain values were observed in fatty lesions (0.46%) compared with fibrous plaques ( P =0.007). After correction for confounding by lipid content, no additional differences in average strain were found between plaques with and without macrophages ( P =0.966). Receiver operating characteristic analysis revealed a sensitivity and a specificity of 100% and 80%, respectively, to identify fatty plaques. The presence of a high-strain spot (strain &gt;1%) has 92% sensitivity and 92% specificity to identify macrophages. Conclusions — To the best of our knowledge, this is the first time that intravascular ultrasound elastography has been validated in vivo. Fatty plaques have an increased mean strain value. High-strain spots are associated with the presence of macrophages.
Barriers and Approaches to the Successful Integration of Palliative Care and Oncology Practice
Authors: Jamie H. Von Roenn, Raymond Voltz, Alain Serrie
Journal: Journal of the National Comprehensive Cancer Network (2013)

As management of patients with cancer is evolving, an increased focus is being placed on individualized patient-centered care. Early integration of palliative care into the overall management of patients with cancer can help achieve this paradigm shift. Despite recommendations for earlier integration of palliative care by national and international societies, several barriers remain to achieving this goal. Survey studies have indicated a significant need for increased education regarding palliative care for both medical undergraduates and postgraduate physicians. Key issues in the early integration of palliative care include relationship-building across multiple health systems and specialties; development of a standardized definition of palliative care, making clear that it should be fully integrated with cancer-directed therapy; identification of physician and nonphysician champions; standardization of tools for patient assessment; education programs designed to meet the needs of health care professionals; and ongoing evaluation to assess program benefits and limitations.
Cytogenetic landscape of paired neurospheres and traditional monolayer cultures in pediatric malignant brain tumors
Authors: Xiumei Zhao, Yi-Jue Zhao, Qi Lin, Litian Yu, Zhigang Liu, Holly Lindsay, Mari Kogiso, Pulivarthi Rao, Xiao-Nan Li, Xinyan Lu
Journal: Neuro-Oncology (2014)

New therapeutic targets are needed to eliminate cancer stem cells (CSCs). We hypothesize that direct comparison of paired CSCs and nonstem tumor cells (NSTCs) will facilitate identification of primary "driver" chromosomal aberrations that can serve as diagnostic markers and/or therapeutic targets.We applied spectral karyotyping and G-banding to matched pairs of neurospheres (CSC-enriched cultures) and fetal bovine serum-based monolayer cultures (enriched with NSTCs) from 16 patient-derived orthotopic xenograft mouse models, including 9 medulloblastomas (MBs) and 7 high-grade gliomas (HGGs), followed by direct comparison of their numerical and structural abnormalities.Chromosomal aberrations were detected in neurospheres of all 16 models, and 82.0% numerical and 82.4% structural abnormalities were maintained in their matching monolayer cultures. Among the shared abnormalities, recurrent clonal changes were identified including gain of chromosomes 18 and 7 and loss of chromosome 10/10q (5/16 models), isochromosome 17q in 2 MBs, and a new breakpoint of 13q14 in 3 HGGs. Chromothripsis-like evidence was also observed in 3 HGG pairs. Additionally, we noted 20 numerical and 15 structural aberrations that were lost from the neurospheres and found 26 numerical and 23 structural aberrations that were only present in the NSTCs. Compared with MBs, the neurosphere karyotypes of HGG were more complex, with fewer chromosomal aberrations preserved in their matching NSTCs.Self-renewing CSCs in MBs and pediatric HGGs harbor recurrent numerical and structural aberrations that were maintained in the matching monolayer cultures. These primary chromosomal changes may represent new markers for anti-CSC therapies.
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update
Authors: Lori Mosca, Carole L. Banka, Emelia J. Benjamin, Kathy Berra, Cheryl Bushnell, Rowena J. Dolor, Theodore G. Ganiats, Antoinette S. Gomes, Heather L. Gornik, Clarissa Gracia, Martha Gulati, Constance K. Haan, Debra R. Judelson, Nora Keenan, Ellie Kelepouris, Erin D. Michos, L. Kristin Newby, Suzanne Oparil, Pamela Ouyang, Mehmet C. Oz, Diana Petitti, Vivian W. Pinn, Rita F. Redberg, Rosalyn Scott, Katherine Sherif, Sidney C. Smith, George Sopko, Robin H. Steinhorn, Neil J. Stone, Kathryn A. Taubert, Barbara A. Todd, Elaine Urbina, Nanette K. Wenger
Journal: Journal of the American College of Cardiology (2007)
Imiquimod Treatment Induces Expression of Opioid Growth Factor Receptor
Authors: Mirjana Urosevic, Patrick A. Oberholzer, Tanja Maier, Jürg Hafner, Elisabeth Laine, Herbert Slade, Bernd Benninghoff, Günter Burg, Reinhard Dummer
Journal: Clinical Cancer Research (2004)

Imiquimod represents a synthetic local immune response modifier that has demonstrated efficacy in clearing basal cell carcinoma. Via interaction with Toll-like receptor 7 on immune cells, imiquimod induces local production of cytokines, such as interferon (IFN)-alpha.To more closely define and elucidate mechanisms leading to basal cell carcinoma clearance in vivo, we examined gene expression profiles of skin basal cell carcinoma before and after treatment with 5% imiquimod cream (Aldara) by using high-density oligonucleotide arrays.We show that imiquimod predominantly induces genes involved in different aspects of immune response. In addition to effects on immunity, imiquimod treatment modulates the expression of genes involved in the control of apoptosis and oncogenesis. Array data indicated that imiquimod treatment induces expression of opioid growth factor receptor, a molecule recently reported to be a target for antitumor antibody responses. Immunohistochemistry revealed in vivo up-regulation of opioid growth factor receptor protein on tumor and on infiltrating cells after treatment. By using basal cell carcinoma cell lines treated with IFN-alpha or imiquimod, we show that opioid growth factor receptor up-regulation is IFN-alpha-mediated, rather then directly imiquimod-mediated. By using tissue microarray containing 52 basal cell carcinomas, we demonstrate opioid growth factor receptor expression in almost half of the cases. Expression of opioid growth factor receptor correlated with a longer recurrence-free period in basal cell carcinoma that recurred after radiotherapy (Kaplan-Meier analysis, P = 0.041).In addition to its immunomodulatory and antiproliferative activity, opioid growth factor receptor seems to have a prognostic significance in basal cell carcinoma patients. Our data add to the growing list of basal cell carcinoma-associated tumor antigens.
CD73-Deficient Mice Have Increased Antitumor Immunity and Are Resistant to Experimental Metastasis
Authors: John Stagg, Upulie Divisekera, Helene Duret, Tim Sparwasser, Michele W.L. Teng, Phillip K. Darcy, Mark J. Smyth
Journal: Cancer Research (2011)

CD73 is a cell-surface enzyme that suppresses immune responses by producing extracellular adenosine. In this study, we employed CD73 gene-targeted mice to investigate the role of host-derived CD73 on antitumor immunity and tumor cell metastasis. We found that CD73 ablation significantly suppressed the growth of ovalbumin-expressing MC38 colon cancer, EG7 lymphoma, AT-3 mammary tumors, and B16F10 melanoma. The protective effect of CD73 deficiency on primary tumors was dependent on CD8(+) T cells and associated with an increased frequency of antigen-specific CD8(+) T cells in peripheral blood and tumors and increased antigen-specific IFN-γ production. Replicate studies in bone marrow chimeras established that both hematopoietic and nonhematopoietic expression of CD73 was important to promote tumor immune escape. Using adoptive reconstitution of T regulatory cell (Treg)-depleted DEREG (depletion of regulatory T cells) mice, we demonstrated that part of the protumorigenic effect of Tregs was dependent on their expression of CD73. CD73-deficient mice were also protected against pulmonary metastasis of B16F10 melanoma cells after intravenous injection. Unexpectedly, we found that the prometastatic effect of host-derived CD73 was dependent on CD73 expression on nonhematopoietic cells. CD73 expression on nonhematopoietic cells, most likely endothelial cells, was critical for promoting lung metastasis in a manner independent from immunosuppressive effects. Notably, in vivo blockade of CD73 with a selective inhibitor or anti-CD73 monoclonal antibody significantly reduced tumor growth and metastasis of CD73-negative tumors. Taken together, our findings indicate that CD73 may be targeted at multiple levels to induce anticancer effects including at the level of tumor cells, Tregs, and nonhematopoietic cells.
How Well Does Whole Genome Sequencing Improve Ability to Detect Association with Asthma in Candidate Genes Compared to Existing GWAS Platforms in African American Populations?
Authors: Nicholas M. Rafaels, Henry R. Johnston, Lili Huang, Sameer Chavan, James G. Wilson, L. Keoki Williams, Lorraine B. Ware, Carole Ober, Deborah A. Meyers, Tina V. Hartert, Marilyn Foreman, Jean G. Ford, Esteban Gonza Burchard, Eugene R. Bleecker, Margaret Taub, Terri H. Beaty, Ingo Ruczinski, Rasika A. Mathias, Kathleen C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2015)
ABC of major trauma. Trauma of the lower urinary tract.
Authors: A Deane
Journal: BMJ (1990)

Bladder injuriesCystogram of a bladder full of haematoma with extravasation of contrast due to a torn anterior bladder wall.The patient required 30 units of blood before bleeding was controlled by selective interna iliac embolisation.* Inspect the urinary meatus for blood * Examine the abdomen for peritonism, perineal bruising, and a high riding prostate * Perform intravenous urography to detect bladder perforation, displaced bladder, upper urinary tract injury Perform cystography to exclude bladder perforation if patient has a catheter in place Perform ascending urethrography (aqueous contrast) to exclude urethral injury (controversial) Management of patients with bulbar injuries * Do not pass a urethral catheter * If the patient passes urine give antibiotics and follow up * If the patient has urinary retention insert a suprapubic catheter with a small calibre and give antibiotics.Perform urethrography after about five days and follow up
Quality of life in anterior cruciate ligament-deficient individuals: a systematic review and meta-analysis
Authors: S R Filbay, A G Culvenor, I N Ackerman, T G Russell, K M Crossley
Journal: British Journal of Sports Medicine (2015)

Background Physical and psychological impairments impacting quality of life (QOL) are common following ACL reconstruction. Rehabilitation alone is an effective alternative to reconstruction for some patients, warranting the investigation of QOL in ACL-deficient individuals. Purpose To report and compare QOL in ACL-deficient individuals with population norms and ACL-reconstructed groups, and investigate relationships between participant characteristics and QOL. Study design Systematic review and meta-analysis. Methods We systematically identified and methodologically appraised all studies reporting QOL in ACL-deficient individuals ≥5 years following ACL rupture. Knee-related and health-related QOL scores in ACL-deficient cohorts were compared to ACL-reconstructed groups using a random-effects meta-analysis. Descriptive comparisons were made with population norms. Results Eleven studies reported QOL in 473 ACL-deficient individuals, a mean of 10 (range 5–23) years following ACL rupture. Eight studies reported knee-related QOL using the Knee injury and Osteoarthritis Outcome Score QOL subscale (KOOS-QOL); scores (mean±SD) ranging from 54±17 to 77±22 were impaired compared to population norms. Health-related QOL, measured with the SF-36 domain scores in five studies, was similar to population norms, but impaired compared to physically active populations. Meta-analysis revealed no significant differences in KOOS-QOL (mean difference (95% CI) 2.9 (−3.3 to 9.1)) and SF-36 scores (for all SF-36 domains except Vitality) between ACL-deficient and ACL-reconstructed groups. Conclusions This systematic review found impaired knee-related QOL in ACL-deficient individuals ≥5 years after ACL rupture, compared to population norms. Meta-analysis revealed similar knee-related QOL in ACL-deficient and ACL-reconstructed groups, and no difference in health-related QOL scores for seven of the eight SF-36 domains.
Biliary Posters
Journal: Gut (2001)

Total colonoscopy was recorded in 21 (84%) AP and in 43 (95.6%)NP using MEI.The median distance to the caecum in AP was 104cm (IQ range,) as compared to 87cm (79-100) in NP (p=0.0009,Mann Whitney U).The median maximum length of colonoscope inserted was 127.5cm (110-155.1) in AP compared to 110cm (105-120) in NP (p=0.0023).The greatest diVerence was in the median length of colonoscope inserted to reach the sigmoiddescending junction, 78.5cm (62.9-94.1) in AP compared to 51.3cm (42.4-61.5) in NP (p<0.0001).This was associated with greater complex looping in the sigmoid colon in AP (5/24) than in NP (1/44)(p=0.0118,chi square).The median time to the caecum was 772sec (613.5-1063) in AP compared to 563.5sec (400.8-853.6) in NP (p=0.0267,Mann Whitney U). Conclusion:Patients with acromegaly are more diYcult to colonoscope than normal patients because they have longer colons, which are more prone to loop formation.
Characteristics of Suicide Attempts of Patients With Major Depressive Episode and Borderline Personality Disorder: A Comparative Study
Authors: P H Soloff, K G Lynch, T M Kelly, K M Malone, J J Mann
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Suicidal behavior is highly prevalent in borderline personality disorder and major depressive episode, although the characteristics of suicide attempts in the two disorders are believed to differ. Comorbidity of borderline personality disorder and major depressive episode may obscure characteristics of suicide attempts that are uniquely related to the psychopathology of each disorder. We compared suicidal behavior in patients with borderline personality disorder, major depressive episode, and borderline personality disorder plus major depressive episode to determine whether characteristics of suicide attempts differed between groups and if aspects of core psychopathology predicted specific attempt characteristics. METHOD: Eighty-one inpatients with borderline personality disorder, including 49 patients with borderline personality disorder plus major depressive episode, were compared to 77 inpatients with major depressive episode alone on measures of depressed mood, hopelessness, impulsive aggression, and suicidal behavior, including lifetime number of attempts, degree of lethal intent, objective planning, medical damage, and degree of violence of suicide methods. RESULTS: No significant differences were found in the characteristics of suicide attempts between patients with borderline personality disorder and those with major depressive episode. However, patients with both disorders had the greatest number of suicide attempts and the highest level of objective planning. An increase in either impulsive aggression or hopelessness or a diagnosis of borderline personality disorder predicted a greater number of attempts. Hopelessness predicted lethal intent in all three groups and predicted objective planning in the group with both disorders. Medical damage resulting from the most serious lifetime suicide attempt was predicted by number of attempts. CONCLUSIONS: Comorbidity of borderline personality disorder with major depressive episode increases the number and seriousness of suicide attempts. Hopelessness and impulsive aggression independently increase the risk of suicidal behavior in patients with borderline personality disorder and in patients with major depressive episode.
Methylation Profiling of Archived Non–Small Cell Lung Cancer: A Promising Prognostic System
Authors: A. Mazin Safar, Horace Spencer, Xiaobo Su, Maureen Coffey, Craig A. Cooney, Luke D. Ratnasinghe, Laura F. Hutchins, Chun-Yang Fan
Journal: Clinical Cancer Research (2005)

Enhanced prognostication power is becoming more desirable in clinical oncology. In this study, we explored the prognostic potential of multigene hypermethylation profiling in non-small-cell lung cancer.We evaluated a panel of eight genes (p16, APC, ATM, hMLH1, MGMT, DAPK, ECAD, and RASSF1A) using methylation-specific PCR in 105 archived specimens of non-small-cell lung cancer representing all stages of the illness. We analyzed the effect of gene methylation status on outcome individually in a cumulative manner and in a combinatorial approach using recursive partitioning to identify methylation profiles, which affect overall survival.In this data set, tumors harboring promoter hypermethylation at two or more genes exhibit similar survival trends to others in the cohort. Using recursive partitioning, three genes (APC, ATM, and RASSF1A) emerged as determinants of prognostic groups. This designation retained its statistical significance even when disease stage and age were entered into a multivariate analysis. Using this approach, patients whose tumors were hypermethylated at APC and those hypermethylated at only ATM (not also at APC or RASSF1A) enjoyed substantially longer 1- and 2-year survival than patients in the remaining groups. In 32 adjacent histologically normal lung tissue specimens, we detected similar methylation abnormalities.Assessment of promoter hypermethylation aberrations may facilitate prognostic profiling of lung tumors, but validation in independent data sets is needed to verify these profiles. This system uses material that is abundantly available with linked outcome data and can be used to generate reliable epigenetic determinants.
Novel Steroid Receptor Phyto-Modulator Compound A Inhibits Growth and Survival of Prostate Cancer Cells
Authors: Alexander Yemelyanov, Jennifer Czwornog, Lajos Gera, Sonali Joshi, Robert T. Chatterton, Irina Budunova
Journal: Cancer Research (2008)

Abstract Androgen receptor (AR)– and glucocorticoid receptor (GR)– mediated signaling play opposite roles in prostate tumorigenesis: AR promotes prostate carcinoma (PC) development, whereas GR acts as a tumor suppressor. Compound A (CpdA) is a stable analogue of an aziridine precursor from the African shrub Salsola tuberculatiformis Botschantzev. It was shown recently that, in model cells, CpdA inhibits AR function and strongly enhances anti-inflammatory function of GR. We determined the effects of CpdA in prostate cells with different AR/GR status: (a) RWPE-1 cells (ARlow/GRlow), (b) PC3 and DU145 cells (GR+/AR−), (c) LNCaP cells (GR−/AR+), and (d) LNCaP-GR cells expressing both receptors. Similar to steroid hormones, CpdA induces nuclear translocation of both receptors in prostate cells. Despite this, CpdA inhibits DNA-binding and transactivation potential of AR. In addition, CpdA inhibits GR-mediated transactivation but induces GR transrepression via inhibition of several transcription factors, including nuclear factor-κB, AP-1, Ets-1, Elk-1, SRF, CRE/ATF, and NFATc. CpdA strongly decreases growth and induces caspase-dependent apoptosis in highly malignant PC3 and DU145 cells and in other AR/GR-expressing PC cells. The cytostatic effect of CpdA is receptor dependent: down-regulation of GR or AR expression drastically attenuates CpdA-induced PC cell growth inhibition. Finally, virtual docking analysis indicates that CpdA shares binding cavities in AR and GR ligand-binding domains with corresponding hormones and forms hydrogen bonds (H-bond) with the same amino acids that are involved in H-bond formation during steroid binding. Overall, our data suggest that CpdA is a unique dual-target steroid receptor modulator that has a high potential for PC therapy. [Cancer Res 2008;68(12):4763–73]
102 NOVEL SUSCEPTIBILITY LOCI FOR PRIMARY SCLEROSING CHOLANGITIS IDENTIFIED BY GENOME-WIDE ASSOCIATION AND REPLICATION ANALYSIS
Authors: T. Folseraas, E. Melum, B. Juran, R.K. Weersma, C. Schramm, T.J. Weismüller, D.N. Gotthardt, K.M. Boberg, M. Janse, E. Buchert, E. Björnsson, L. Henckaerts, C. Rust, A. Teufel, A. Bergquist, E. Ryu, J.R. Hov, K. Holm, C.Y. Ponsioen, H. Runz, M. Sterneck, S. Vermeire, C. Wijmenga, U. Beuers, E. Schrumpf, M.P. Manns, K. Lazaridis, S. Schreiber, A. Franke, T.H. Karlsen
Journal: Journal of Hepatology (2011)