tbuckley/cabot-search huggingface dataset:
Losartan, an angiotensin II type 1 receptor antagonist, lowers hematocrit in posttransplant erythrocytosis.
Authors: B A Julian, R R Brantley, C V Barker, T Stopka, R S Gaston, J J Curtis, J Y Lee, J T Prchal
Journal: Journal of the American Society of Nephrology (1998)

The mechanism by which angiotensin-converting enzyme inhibitors reduce red cell mass in renal transplant recipients with erythrocytosis is unclear. To examine the role of angiotensin II in this disorder, losartan (a competitive antagonist of the angiotensin II type 1 [AT1] receptor) was administered to 23 patients with erythrocytosis. Fourteen patients took 25 mg/d for 8 wk; nine others were treated with 50 mg/d for 8 wk. Hematocrit decreased from 0.527 +/- 0.027 to 0.487 +/- 0.045 after 8 wk (P < 0.01)--by at least 0.04 in 19 patients. Decrement in hematocrit in the initial 8 wk of therapy was significantly greater in patients administered 50 mg/d than in patients on 25 mg/d. Twelve of 14 patients initially treated with 25 mg/d showed a small change in hematocrit; the dose was increased to 50 mg/d for 8 more wk. Hematocrit decreased from 0.528 +/- 0.030 before losartan treatment to 0.483 +/- 0.055 after 16 wk (P < 0.01). After therapy, serum erythropoietin significantly decreased in eight patients with elevated baseline levels, but not in 15 patients with normal baseline levels; however, hematocrit significantly decreased in both groups. Losartan was withdrawn in 16 patients; hematocrit increased from 0.440 +/- 0.057 to 0.495 +/- 0.049 after 8.9 +/- 7.5 wk (P < 0.001), without change in serum erythropoietin. Thus, specific blockade of AT1 receptors inhibited erythropoiesis, suggesting a pathogenic role for angiotensin II in posttransplant erythrocytosis.
Abstract 11740: Identification of a Mechanism vy Which Common Blood Pressure Genetic Variant in the Nppa Gene Regulates Anp Levels
Authors: Pankaj Arora, Connie Wu, Abigail May Khan, Donald Bloch, Brandi Davis-Dusenbery, Anahita Ghorbani, Ester Spagnolli, Andrew Martinez, Allicia Ryan, Laurel T Tanish, Samuel Kim, Karen Klahr Miller, Akiko Hata, Federica del Monte, Tara Minaker Holmes, Emmanuel Buys, Kenneth D Bloch, Thomas J Wang, Christopher Newton-Cheh
Journal: Circulation (2012)

Pankaj Arora, 2012 Finalist and Presenting Author
Heterochromatin Protein HP1γ Promotes Colorectal Cancer Progression and Is Regulated by miR-30a
Authors: Ming Liu, Feifei Huang, Dan Zhang, Junyi Ju, Xiao-Bin Wu, Ying Wang, Yadong Wang, Yupeng Wu, Min Nie, Zhuchen Li, Chi Ma, Xi Chen, Jin-Yong Zhou, Renxiang Tan, Bo-Lin Yang, Ke Zen, Chen-Yu Zhang, Yu-Gen Chen, Quan Zhao
Journal: Cancer Research (2015)

Colorectal cancer pathogenesis remains incompletely understood. Here, we report that the heterochromatin protein HP1γ is upregulated commonly in human colorectal cancer, where it promotes cell proliferation in vitro and in vivo. Gene-expression and promoter-binding experiments demonstrated that HP1γ directly regulated CDKN1A (p21(Waf1/Cip1)) in a manner associated with methylation of histone H3K9 on its promoter. We identified miR-30a as a tumor-suppressive microRNA that targets HP1γ in vitro and in vivo to specifically suppress the growth of colorectal cancer in mouse xenograft models. MiR-30a was widely downregulated in primary human colorectal cancer tissues, where its expression correlated inversely with high levels of HP1γ protein. Our results identify a new miR-30a/HP1γ/p21 regulatory axis controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities.
Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma.
Authors: M S Kaminski, K R Zasadny, I R Francis, M C Fenner, C W Ross, A W Milik, J Estes, M Tuck, D Regan, S Fisher, S D Glenn, R L Wahl
Journal: Journal of Clinical Oncology (1996)

PURPOSE The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy. PATIENTS AND METHODS Patients were first given tracelabeled doses of 131I-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose (15 to 20 mg) labeled with a quantity of 131I that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by an infusion of 135 mg of unlabeled anti-B1 one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1. RESULTS Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment. CONCLUSION Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.
Clinical experience with extended lymph node dissection during radical prostatectomy
Authors: G. Sonpavde, K. Slawin, J. M. Levitt, L. Guariguata
Journal: Journal of Clinical Oncology (2006)

14545 Background: The value of the extent of lymph node dissection at radical prostatectomy remains controversial. We report our experience with extended lymph node dissection in patients undergoing open radical prostatectomy. Methods: 201 consecutive patients with cT1c-cT3a prostate cancer who underwent open radical prostatectomy with an extended regional lymph node (LN) dissection of up to six packets (iliac, hypogastric, and obturator; right and left) by a single surgeon at The Methodist Hospital between July 2002 and April 2004 were studied. No patient was treated with adjuvant radiation or hormonal therapy before elevated PSA levels were observed. Ultrasensitive PSA (uPSA) using the 3rd generation Immulite assay (DPC) was performed periodically beginning at 6 weeks post operatively. A uPSA level ≥ 0.03 ng/mL and rising on at least one subsequent uPSA obtained at least six weeks later was classified as a biochemical recurrence (BCR). Results: The mean patient age was 59 years at the time of surgery (median, 59; range, 39 to 73 years). Median follow-up after surgery was 21 months (range 1–37 months). Gleason Score was ≤ 6, 7, and 8–10 in 37%, 53% and 10% of patients, respectively. Sixty-two patients had extra prostatic extension and 16 patients had seminal vesicle involvement. A total of 3125 pelvic lymph nodes were removed (per patient: mean, 15.64; median, 15; range 4–42). Of these 22 LN (0.71%) were positive in 11 (5.5%) patients. By specified region, 2/1775 (0.23%) of iliac nodes, 6/642 (0.93%) of hypogastric nodes and 9/708 (1.27%) of obturator nodes were positive. Of the 11 patients with positive LN, 3/11 (27.27%) had positive iliac nodes, 6/11 (54.54%) had positive hypogastric nodes, and 6/11 (54.54%) had positive obturator nodes. Using a very stringent definition of BCR in order to compensate for the relatively short follow-up period, the 2 year progression-free survival (PFS) for patients with at least one positive LN was 37.5%. Conclusions: Extended LN dissection may alter the biology of early nodal metastatic prostate cancer and lead to longterm PFS without additional therapy. A higher percentage of patients and nodes are positive in the hypogastric and obturator regions, supporting the rationale to include these with the iliac nodes when performing LN dissection. No significant financial relationships to disclose.
Differential diagnosis of pandemic (H1N1) 2009 infection by detection of haemagglutinin with an enzyme-linked immunoassay
Authors: Q. Yuan, X.-D. Cheng, B.-C. Yang, Q.-B. Zheng, Y.-X. Chen, Q.-R. Chen, F. Zeng, R. Zhang, S.-X. Ge, X.-K. Hao, H. Chen, J. Zhang, N.-S. Xia
Journal: Clinical Microbiology and Infection (2010)
Literature Survey of Bacterial, Fungal, and &lt;italic&gt;Drosophila&lt;/italic&gt; Assay Systems Used in the Evaluation of Selected Chemical Compounds for Mutagenic Activity&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M M Brown, J S Wassom, H V Malling, M D Shelby, E S Von Halle
Journal: JNCI Journal of the National Cancer Institute (1979)

Literature reports were surveyed, with results noted from experiments in seven nonmammalian assay systems used for the detection of mutagenicity or other related genetic effects. A comparison was made of the activities of 54 selected noncarcinogens, procarcinogens, and ultimate carcinogens as revealed by these test systems. Of the compounds tested, 49 (91%) were active in one or more of the assays, and 42 (78%) were positive in at least one system without having to be metabolically activated. In one or more test systems, 17/17 (100%) of the ultimate carcinogens, 27/28 (96%) of the procarcinogens, and 6/9 (67%) of the noncarcinogens were positive. The Ames Salmonella-microsome assay responded with increased mutation frequency to 37/44 (84%) of the carcinogenic compounds but to only 2/8 (25%) of the noncarcinogens tested. The Drosophila system responded to 19/21 (90%) of the carcinogens and to 3/6 (50%) of the noncarcinogens. Prophages were induced when lysogenic bacteria were exposed to 12/21 (57%) of the carcinogens, but not enough tests were done with the noncarcinogens (1/3, or 33%) for a comparison. The other systems reviewed, such as the killing of repair-deficient bacteria, mutations in Escherichia coli and Neurospora crassa, and the host-mediated assay, were not challenged by enough of the compounds for valid comparisons.
25-hydroxide-vitamin D induces TSLP expression in human bronchial epithelial cells via the VDUP1 pathway
Authors: Haijin Zhao, Dan Zhang, ChengHua Peng, Yang Xia, Shaoxi Cai
Journal: European Respiratory Journal (2012)

Background:  Airway epithelial cells (AEC) express 1α-hydroxylase and are able to covert 25-hydroxide–vitamin D (25[OH]D) to an active form that plays a role in mucosal immunity. Thymic stromal lymphopoietin (TSLP), a cytokine mainly produced by AECs during allergic asthma reactions, plays a critical role in the activation of Th2 inflammatory responses. Therefore, we hypothesized that 25(OH)D would enhance the expression of TSLP in airway epithelia (16HBE cell line) and that vitamin D3 upregulated protein 1 (VDUP1) could be involved in this process.   Methods:  16HBE cells were cultured with 25(OH)D, and TSLP and VDUP1 mRNA and protein expression were then determined by means of quantitative PCR, ELISA, and Western blot analysis, as appropriate. The role of VDUP1 on TSLP expression was assessed in untreated and 25(OH)D-treated 16HBE cells where VDUP1 levels were manipulated via overexpression or siRNA-mediated silencing. The effect of 10 -6  M itraconazole, a chemical inhibitor of 1α-hydroxylase, on the expression of TSLP was also determined.   Results:  25(OH)D significantly induced TSLP and VDUP1 mRNA expression in 16HBE cells. Silencing of VDUP1 dramatically inhibited 25(OH)D-mediated induction of TSLP, and overexpression of VDUP1 upregulated baseline TSLP expression and 25(OH)D-induced TSLP expression in 16HBE cells. Inhibition of 1α-hydroxylase reduced 25(OH)D-induced TSLP expression in 16HBE cells.   Conclusion:  These data demonstrated that vitamin D increased TSLP expression in 16HBE cells via upregulation of VDUP1.
Airway bacterial colonization is associated with low vitamin D serum levels in children with cystic fibrosis
Authors: Jasna Rodman, Tita Butenko, Ana Kotnik, Katja Seme, Uros Krivec
Journal: European Respiratory Journal (2013)

Background: Recent studies suggest that vitamin D has significant anti-infective actions. Appropriate 25-hydroxyvitamin D (25OHD) serum level can be linked to enhanced airways’ antibacterial mechanisms in cystic fibrosis (CF) patients.

Aim: To determine whether 25OHD serum level correlates with airway bacterial colonization in children with CF.

Methods: Data were extracted from patients’ medical documentation. 25OHD serum level was determined by immunoassay once per year. Chronic airway colonization with Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) was defined by Leeds criteria. Additionally, presence of Stenotrophomonas maltophilia (SM), Acinetobacter baumanii (AB), methicillin-resistant Staphylococcus aureus (MRSA) and Achromobacter xylosoxidans (AX) in respiratory samples was assessed.

Results: Sixty-one 25OHD serum levels from 27 children (14 males), mean age 7.9 (± 1.8) years were recorded in a 5–year period. Mean 25OHD serum levels was 79.1 (± 25.9) nmol/l. Deficiency (level < 75 nmol/l) was present in 49.2 % of cases. No PA chronic colonization was identified, but SA chronic colonization was frequent (90.2%). SA colonized children had lower 25OHD serum levels (76.3 (± 24.5) vs. 104.8 (± 29.2) nmol/l, P < 0.005). SM colonization was present in 13.1%, AB and AX both in 4.9% of patients, neither was significantly correlated with serum 25OHD levels.

Conclusion: Lower serum 25OHD levels are associated with chronic airway SA colonization in CF children. The results emphasize the importance of appropriate vitamin D supplementation in these patients.
Efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy: a phase 2, randomised, double-blind, placebo-controlled trial
Authors: Remigio M Olveda, Luz P Acosta, Veronica Tallo, Palmera I Baltazar, Jenny Lind S Lesiguez, Georgette G Estanislao, Edna B Ayaso, Donna Bella S Monterde, Antonio Ida, Nora Watson, Emily A McDonald, Hannah W Wu, Jonathan D Kurtis, Jennifer F Friedman
Journal: The Lancet Infectious Diseases (2015)
MYC/PGC-1α Balance Determines the Metabolic Phenotype and Plasticity of Pancreatic Cancer Stem Cells
Authors: Patricia Sancho, Emma Burgos-Ramos, Alejandra Tavera, Tony Bou Kheir, Petra Jagust, Matthieu Schoenhals, David Barneda, Katherine Sellers, Ramon Campos-Olivas, Osvaldo Graña, Catarina R. Viera, Mariia Yuneva, Bruno Sainz, Christopher Heeschen
Journal: Cell Metabolism (2015)
Less Can Be More for Gene Dose and Drug Sensitivity
Authors: Susanne A. Gatz, Janet M. Shipley
Journal: Clinical Cancer Research (2015)

Abstract CDK4 is preclinically validated as a therapeutic target in PAX3–FOXO1 fusion gene-positive rhabdomyosarcomas. Pharmacologic targeting showed sensitivity but, contrary to expectation, CDK4 genomic amplification and overexpression associated with 25% of cases that exhibited the lowest sensitivities. This emphasizes the importance of tumor-specific preclinical studies to define and understand drug sensitivity. Clin Cancer Res; 21(21); 4750–2. ©2015 AACR. See related article by Olanich et al., p. 4947
Sleep related respiratory disorders (SRD) in patients with usual interstitial pneumonia (UIP)
Authors: Massimiliano Desideri, Laura Maria Tavanti, Letizia Marconi, Elena Mariancini, Stefania Giannessi, Lucia Lupetti, Antonio Palla
Journal: European Respiratory Journal (2013)

Aim: Aim of our study was to analyze SRD in an outpatient population with UIP without diurnal respiratory failure.  Materials and methods: Patients with UIP and without respiratory failure, assessed with awake arterial blood gas (ABG) analysis, who had been followed up in our Pulmonary Unit were asked to participate. All patients performed full clinical and functional lung evaluation and completed an Epworth Sleepiness Scale (ESS) questionnaire before undergoing nocturnal cardio-respiratory monitoring (nCRM).  Results: Fifteen patients were recruited (73% males, mean age 70.9±6.8 years). Thirteen out of 15 (86.7%) had Obstructive Sleep Apnea Syndrome (OSAS). Seven patients (46.7%) had mild OSAS (AHI, 5 to 15 events per hour), and 6 subjects (40%) had moderate to severe OSAS (AHI > 15 events per hour). Only 2 subjects(13.3%) had a normal AHI. Most of sleep disordered breathing events in patients with OSAS were hypopneas. One third of subjects had a HbO2   Conclusion: OSAS is very frequent in patients with UIP. Hypopneas were more commonly observed than apneas. ESS score is not a good predictor for OSAS in such population. Therefore, a nCRM should be reccommanded in patient with UIP.
Moral Concerns of Different Types of Patients in Clinical <i>BRCA1/2</i> Gene Mutation Testing
Authors: Guido Goelen, Adelheid Rigo, Maryse Bonduelle, Jacques De Grève
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Implementing predictive genetic testing for a severe and common chronic disease such as breast cancer may raise unique ethical problems. Here we report on moral concerns experienced by patients in the setting of genetic counseling based on BRCA1/2 gene testing. PATIENTS AND METHODS: Patients were members of breast or breast/ovarian cancer families in a consecutive series of 100 families who received counseling at a familial cancer clinic. The patients' moral concerns were identified using the grounded theory approach in the qualitative analysis of verbal transcripts of 45 counseling sessions. Included were sessions with patients who had breast and ovarian cancer, as well as their male and female relatives, before and after the specific BRCA1/2 gene mutation was identified in the family, and before and after those who opted for mutation analysis were informed of their carrier status. RESULTS: There is an association of BRCA1/2 gene mutation carrier status and specific topics of moral concern. The moral preoccupations of patients with breast and ovarian cancer (probable carriers) related to their being instrumental in the detection of the specific mutation segregating in the family. The preoccupations of possible carriers concerned their own offspring. Individuals who tested positive (proven carriers) were concerned with issues of confidentiality. Patients who tested negative (proven noncarriers) were concerned with helping siblings and other relatives. CONCLUSION: Knowledge of the moral concerns of subjects in the study sample may help health care providers be aware of the moral concerns of their own patients. This report may also contribute to the debate on predictive testing for familial adult-onset diseases from the patient's perspective.
Paediatric Posters
Authors: W.G. MacKay, A.J. Shepherd, C.P. Doherty, M. Hossack, C.L. Williams, L.T. Weaver
Journal: Gut (2001)

Background/aim: The vast majority of West African adults are colonised with H. pylori and most children acquire the infection in early life. There is an inverse relationship between the prevalence of H. pylori and socioeconomic development throughout the world. In Greater Glasgow 50% of postcodes belong to Deprivation Categories 5–7 (poorest socioeconomic status). Our aim was to study intrafamilial patterns of H. pylori infection in Glasgow and to identify possible modes of spread.

Methods: The families of 32 children, who presented at the RHSC Glasgow with suspected H. pylori -related disease, were studied. H. pylori status was determined by faecal antigen testing, a method that we have validated against the urea breath test in children.

Results: The families consisted of 57 parents, 47 siblings and 32 index children. Of these 136 subjects 93% provided stool samples. The prevalence of H. pylori in this sample was 35% (41% of parents and 30% of children). Those index children who were of Dep Cats 5–7 were 7 times more likely to be infected with H. pylori than those of Dep Cats 1–4 (p=0.03 Fisher's exact test). Index children whose siblings were H. pylori +ve were 9 times more likely to be H. pylori +ve themselves (p=0.06). Both the H. pylori status of parents (p=0.3, OR=2) and family size (p=0.6, OR=1) were not significantly related to the H. pylori status of the index child.

Conclusions: Poor socioeconomic status and having an H. pylori infected sibling are significant risk factors for …
Multiplexed cytokine and chemokine profiling in patients with latent tuberculosis infection: Treatment effect
Authors: Patricio Escalante, Tobias Peikert, Virginia P. Van Keulen, Courtney L. Erskine, Marshall D. Behrens, Louis A. Schenck, Andrew H. Limper
Journal: European Respiratory Journal (2014)

Rationale:   Available tests for latent tuberculosis infection (LTBI) suboptimally predict the risk of tuberculosis (TB) reactivation. While LTBI treatment greatly reduces TB reactivation risk, biomarkers to identify these high-risk patients are lacking. Cytokine-chemokine profiles of  ex vivo  antigen-challenged peripheral blood mononuclear cells (PBMCs) reflect antigen-specific T-cell activation and we hypothesize that these cytokine-chemokine signatures can be utilized to assess the reactivation potential of LTBI patients.    Objective:   To compare cytokine-chemokine signatures of antigen-specific activate PBMCs to Interferon-g release assays in patients with untreated and treated LTBI.    Methods:   Multiplexed analysis of 17 cytokines and chemokines in the cell culture supernatants of  ex vivo  antigen-stimulated PMBC samples. PBMCs were stimulated with either CFP-10/ESAT-6 peptides, PPD, or controls. Multiplexed immune profiles were analyzed for each group and adjusted for age and BCG vaccination status using mixed factorial approach.    Results:  After adjustment for age and BCG vaccination status, analysis showed statistical significantly higher levels of TNF-α, IL-2, IL-23, MIP-1α and MIP-1β (pg/mL) in untreated (N=13) compared to treated LTBI patients (N=6), ( P      Conclusion:   These findings suggest that this novel multiplexed cytokine-chemokine profiling might be valuable for TB reactivation assessment. Longitudinal studies would be needed to elucidate the predictive value of this novel immunodiagnostic approach.