tbuckley/cabot-search huggingface dataset:
An Adenovirus Encoding Proapoptotic Bax Induces Apoptosis and Enhances the Radiation Effect in Human Ovarian Cancer
Authors: Waleed O. Arafat, Jesús Gómez-Navarro, Jialing Xiang, Mack N. Barnes, Parameshwar Mahasreshti, Ronald D. Alvarez, Gene P. Siegal, Ahmed O. Badib, Donald Buchsbaum, David T. Curiel, Murray A. Stackhouse
Journal: Molecular Therapy (2000)

Overexpression of proapoptotic Bax favors death in cells resistant to ionizing radiation. We hypothesized that expression of Bax via adenoviral-mediated gene delivery could sensitize radiation-refractory cells to radiotherapy. An inducible Bax recombinant adenovirus (Ad/Bax) had been generated using the Cre/loxp system. Human ovarian cancer cell lines and primary, patient-derived cancer cells from ascites were irradiated and infected with the Ad/Bax and an expression-inducing vector, Ad/Cre. Cell death was evaluated by crystal violet staining, fluorescence-activated cell sorter analysis of Annexin V, and colony formation assay (cell lines only). To further characterize the mechanism of death, cell morphology was examined by nuclear staining with Hoechst 33258. Lastly, to evaluate the capacity of the combined treatment to inhibit tumor growth, mice were injected subcutaneously with ovarian cancer cells exposed to Bax, radiation therapy (RT), or both, and tumor size was measured periodically. Infection of the cancer cell lines and primary cells with both Ad/Bax and Ad/Cre significantly enhanced sensitivity to ionizing radiation, achieving high levels of cell killing in short-term assays. In addition, the combination of Bax and radiotherapy reduced the survival fraction of cell lines 2 logs in standard colony-forming assays. Investigation into the involved mechanism suggests that Bax-mediated radiosensitization occurs through both apoptosis and necrosis pathways. Further, mice subcutaneously injected with ovarian tumor cells previously treated with radiation, or with radiation and irrelevant viruses, consistently developed tumor nodules. In addition, approximately 80% of injections were followed by tumor formation after treatment with Ad/Bax and Ad/Cre alone. In contrast, tumor formation was completely inhibited after combined treatment with Ad/Bax and Ad/Cre and radiation. Augmentation of the effect of radiotherapy on human ovarian cancer cells and primary cancer cells from patients via a recombinant adenovirus encoding Bax is feasible.
Complete Inhibition of Occurrence of Spontaneous Hepatomas in Highly Susceptible (C3H × YBR)F&lt;sub&gt;1&lt;/sub&gt; Male Mice by Hypophysectomy
Authors: W. E. Heston
Journal: JNCI Journal of the National Cancer Institute (1963)

No hepatomas occurred in genetically highly susceptible AvA and Aa male (C3H × YBR)F1 hybrid mice hypophysectomized at 6 weeks of age and maintained to the advanced age of 16 months. Hepatomas were found in 100 percent of the intact control AvA male hybrids of the same age, with an average of 5.6 hepatomas per animal, and in 88 percent of the intact control Aa male hybrids of the same age, with an average of 3 hepatomas per animal. The greater occurrence of hepatomas in the AvA than in the Aa controls confirms the previous observation that the Av gene increases the occurrence of spontaneous hepatomas. The effect, on occurrence of neoplasms, of this gene and of other factors that influence normal growth is discussed.
LRRC26 Is a Functional BK Channel Auxiliary γ Subunit in Arterial Smooth Muscle Cells
Authors: Kirk W. Evanson, John P. Bannister, M. Dennis Leo, Jonathan H. Jaggar
Journal: Circulation Research (2014)

Smooth muscle cell (myocyte) large-conductance calcium (Ca)(2+)-activated potassium (BK) channels are functionally significant modulators of arterial contractility. Arterial myocytes express both pore-forming BKα and auxiliary β1 subunits, which increase channel Ca(2+) sensitivity. Recently, several leucine-rich repeat containing (LRRC) proteins have been identified as auxiliary γ subunits that elevate the voltage sensitivity of recombinant and prostate adenocarcinoma BK channels. LRRC expression and physiological functions in native cell types are unclear.Investigate the expression and physiological functions of leucine-rich repeat containing protein 26 (LRRC26) in arterial myocytes.Reverse transcription polymerase chain reaction and Western blotting detected LRRC26 mRNA and protein in cerebral artery myocytes. Biotinylation, immunofluorescence resonance energy transfer microscopy, and coimmunoprecipitation indicated that LRRC26 was located in close spatial proximity to, and associated with, plasma membrane BKα subunits. LRRC26 knockdown (RNAi) reduced total and surface LRRC26, but did not alter BKα or β1, proteins in arteries. LRRC26 knockdown did not alter Ca(2+) sparks but reduced BK channel voltage sensitivity, which decreased channel apparent Ca(2+) sensitivity and transient BK current frequency and amplitude in myocytes. LRRC26 knockdown also increased myogenic tone over a range (40-100 mm Hg) of intravascular pressures, and reduced vasoconstriction to iberiotoxin and vasodilation to NS1619, BK channel inhibitors and activators, respectively. In contrast, LRRC26 knockdown did not alter depolarization (60 mmol/L K(+))-induced vasoconstriction.LRRC26 is expressed, associates with BKα subunits, and elevates channel voltage- and apparent Ca(2+) sensitivity in arterial myocytes to induce vasodilation. This study indicates that arterial myocytes express a functional BK channel γ subunit.
CXCR3 ligands are augmented during the pathogenesis of pulmonary sarcoidosis
Authors: A. Busuttil, S. S. Weigt, M. P. Keane, Y. Y. Xue, V. Palchevskiy, M. D. Burdick, C. Huang, D. A. Zisman, M. Fishbein, J. P. Lynch, R. M. Strieter, R. M. Elashoff, J. A. Belperio
Journal: European Respiratory Journal (2009)

We and other investigators have hypothesised that the CXC chemokine receptor (CXCR)3/CXCR3 ligand biological axis is involved in the formation of sarcoid lung granulomas; however, significant discrepancies in the current literature remain. In an effort to clarify previous conflicting findings, we performed the largest observational study to date of interferon-inducible ELR - (lacking the sequence glutamic acid–leucine–arginine) CXC chemokines in sarcoid bronchoalveolar fluid (BALF). BALF chemokine levels from sarcoid patients (n = 72) and healthy controls (n = 8) were measured with the ELISA method. Immunohistochemical staining was performed for CXCR3 and its ligands. BALF CXC chemokine ligand (CXCL)10 levels from sarcoid patients were not significantly increased compared with controls. BALF CXCL11 levels from sarcoid patients demonstrated a trend towards elevation; subgroup analysis by stage showed significant BALF CXCL11 elevation in stage I sarcoid patients compared with controls. BALF CXCL9 levels were elevated from sarcoid patients compared with controls. CXC11, CXCL9 and CXCR3 were expressed from epithelioid histiocytes, multinucleated giant cells and other inflammatory cells forming sarcoid lung granulomas. Our data suggest that CXCL9 and CXCL11 are important mediators in recruiting CXCR3-expressing cells. Importantly, we have made the novel observation that both lymphocytes and cells of monocyte linage express CXCR3 and are involved in the formation of sarcoid lung granulomas.
Effect of Sucrose-Containing Snacks On Blood Glucose Control
Authors: Joyce E Wise, Kathryn S Keim, Jacqueline L Huisinga, Pamela A Willmann
Journal: Diabetes Care (1989)

To determine whether ingestion of sucrose-containing snacks would affect blood glucose (BG) control, 16 subjects with insulin-dependent diabetes mellitus participated in a 5-day double-blind study at a diabetes camp. Eight subjects in the sucrose group ate sucrose-sweetened snacks twice a day, and 8 subjects in the control group ingested snacks that were sweetened with aspartame. The percentage of total daily calories derived from added sucrose was 7% for the sucrose group and 1% for the control group. Metabolic control was assessed by daily capillary BG measurements obtained before meals and the bedtime snack and by determination of serum fructosamine (F) concentrations on arrival at camp (day 0) and after 5 days on the study protocol (day 5). No significant difference was seen between the groups on day 0 (sucrose group [mean ± SD]: BG 9.9 ± 3.6 mM, F 3.54 ± 0.38 mM; control group: BG 9.1 ± 2.8 mM, F 3.74 ± 0.71 mM) or day 5 (sucrose group: BG 8.8 ± 2.6 mM, F 2.94 ± 0.32 mM; control group: BG 7.4 ± 2.8 mM, F 2.92 ± 0.59 mM). We conclude that ingestion of sucrose, added to snacks in an amount up to 7% of total energy intake, does not adversely affect short-term BG control.
Phase I Trial of the Cyclin-Dependent Kinase Inhibitor Flavopiridol in Combination with Docetaxel in Patients with Metastatic Breast Cancer
Authors: Antoinette R. Tan, Xiaowei Yang, Arlene Berman, Suoping Zhai, Alex Sparreboom, Allyson L. Parr, Catherine Chow, Jaime S. Brahim, Seth M. Steinberg, William D. Figg, Sandra M. Swain
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this study was to determine the toxicities and characterize the pharmacokinetics of docetaxel and flavopiridol in patients with metastatic breast cancer. Experimental Design: Docetaxel was administered at an initial dose of 60 mg/m2 followed in 24 hours by a 72-hour infusion of flavopiridol at 50 mg/m2/d every 3 weeks. Because dose-limiting myelosuppression occurred, the schedule was amended to docetaxel, 50 mg/m2, followed by escalating doses of flavopiridol (starting dose, 26 mg/m2/d) as a 1-hour infusion daily for 3 days. Pharmacokinetic studies were performed. Ki67, p53, and phosphorylated retinoblastoma protein (phospho-Rb) in paired tumor and buccal mucosa biopsies (obtained pre- and posttreatment) were examined by immunohistochemistry. Results: Eleven patients were enrolled. Five patients received docetaxel and 72-hour flavopiridol. Dose-limiting toxicity was grade 4 neutropenia. Six patients received docetaxel and 1-hour flavopiridol, and the dose-limiting toxicity was grade 3 hypotension. Pharmacokinetics of flavopiridol and docetaxel were consistent with historical data. Nuclear staining with p53 increased and phospho-Rb decreased in 10 pairs of buccal mucosa biopsies posttreatment (P = 0.002 and P = 0.04, respectively). No significant changes in Ki67, p53, or phospho-Rb were detected in six paired tumors. Two patients sustained stable disease for &amp;gt;3 months (72-hour flavopiridol), and one partial response was observed (1-hour flavopiridol). Conclusions: Docetaxel combined with 72-hour flavopiridol was not feasible because of dose-limiting neutropenia. Dose escalation of a 1-hour infusion of flavopiridol with docetaxel was also not possible. The changes in p53 and phospho-Rb in buccal mucosa suggest that a biological effect with flavopiridol was achieved.
The Lumleian Lectures on the Tongue as an Indication of Disease
Authors: W. H. Dickinson
Journal: BMJ (1888)

LECTURB III.Dryness.I sow come to the consideration of dryness of the tongue and its causes.A glance at the annexed table will suffice to show Iow largely this depends on constitutional and how little on local circumstances.Concomitant of Dryness of the Tongue.Cae Tongue dry, irrespective of other qualities... 113 Pyrexia (temperature 102°o r over) ... ... 37 Temperature not above normal ... ... ... 39 Discharge by simple diarrhea or dysentery ... 6 Discharge, diarrhceal or other, connected with larda- ceous disease ... ...
Average length of a flaccid and erect penis is published to help counsellors
Authors: J. Wise
Journal: BMJ (2015)

A systematic review that included more than 15 000 men has found that the average length of a flaccid penis is 9.16 cm and an erect penis 13.12 cm.

The research, published in the journal BJU International ,1 includes graphical diagrams, or nomograms, to show the range of male penis size measurements across all ages and races. The study authors said that the findings may be helpful when counselling men …
Inhaler technique – A time to re-educate patients?
Authors: Markos Bakalis, Emily Morris, Laura Ballance, Dilip Nazareth, Duncan Gordon Fullerton
Journal: European Respiratory Journal (2014)

Background:  The benefit of inhaled therapy depends on adequate airway drug deposition, and it is essential that patients are educated in inhaler use, and technique assessed at least once every 15 months 1 .   Aim:  This study aims to evaluate inhaler technique in patients, with a view to implementing change if needed.   Methods  :  Inpatients with no significant cognitive impairment, who had been prescribed inhalers for any respiratory condition, were randomly selected. Inhaler technique was assessed by a chest physician, using the patients9 own inhalers. A scoring system 2  evaluating each domain (1 point for each) – preparation, expiration, inspiration and breath holding was used.   Results  :  81 (42% male) patients (mean age 73 ± 13 years) using 121 devices were evaluated. 75% had previously been shown how to use the device (family physician 51%, nurse 26%, pharmacist 8%, hospital doctor 5%). Table 1 summarises the main results. MDI9s (x 2 :8.5; p=0.03) and MDI9s plus spacer (x 2 :12.17; p=0.02) were most likely to be used adequately or well.   Conclusions  :  Many patients have inadequate inhaler technique. There is a need to review drug delivery devices at every given opportunity to ensure the patient is using the correct drug and device effectively.   References:   1.The NHS Information Centre for health and social care.  National Quality and Outcomes Framework Achievement Data 2008/09 , September 2009  2. Hilton S. Br J Gen Pract. 1990 Dec;40(341):505-6.
P83 Relations of Different Quality of Life Tools to Subsequent Mortality and Readmission of Patients Surviving Hospitalisation For Acute Exacerbations of COPD: Abstract P83 Table 1
Authors: J Steer, GJ Gibson, SC Bourke
Journal: Thorax (2012)

<h3>Background</h3> In patients hospitalised with acute exacerbations of COPD (AECOPD), quality of life (QoL) scores have been associated with subsequent mortality and readmission. We have investigated which of several QoL indices are most closely related to subsequent outcome. <h3>Methods</h3> 183 patients with AECOPD surviving to hospital discharge were identified prospectively. Baseline clinical information and subsequent mortality and readmission over 12 months were recorded. QoL was assessed at discharge using: the St. George’s Respiratory Questionnaire (SGRQ); the Chronic Respiratory Questionnaire (CRQ); the Hospital Anxiety and Depression Scale (HADS); and the Nottingham Extended Activities of Daily Living Scale (NEADL) and relationships between QoL and each outcome were analysed. <h3>Results</h3> Mean (SD) age was 69.0 (9.0) years and most patients: were female (58.5%); had severe airflow obstruction (mean (SD) FEV1 40.2 (17.3) % predicted); and were of normal weight (mean (SD) BMI 26.2 (7.0) kgm2). 130 (71%) patients were readmitted during the year following discharge, with a median number of readmissions of 1 (IQR 0 to 3; range 0 to 15). The mortality rates at 3, 6 and 12 months following discharge were 6.6%, 10.4% and 18.0% respectively. Self-reported measures of activity (SGRQ Activity and NEADL) were the only QoL indices significantly associated with both mortality and readmission. The relations of SGRQ Impacts and HADS Depression to mortality showed nonsignificant trends, but no other QoL domains were associated with readmission (table 1). <h3>Conclusion</h3> Measures of self-reported activity at discharge were the most closely associated with both subsequent mortality and readmission and are likely to be the most useful of the QoL indices studied for predicting clinical outcome.
An inversion involving the mouse Shh locus results in brachydactyly through dysregulation of Shh expression
Authors: Michael Niedermaier, Georg C. Schwabe, Stephan Fees, Anne Helmrich, Norbert Brieske, Petra Seemann, Jochen Hecht, Volkhard Seitz, Sigmar Stricker, Gundula Leschik, Evelin Schrock, Paul B. Selby, Stefan Mundlos
Journal: Journal of Clinical Investigation (2005)

Short digits (Dsh) is a radiation-induced mouse mutant. Homozygous mice are characterized by multiple defects strongly resembling those resulting from Sonic hedgehog (Shh) inactivation. Heterozygous mice show a limb reduction phenotype with fusion and shortening of the proximal and middle phalanges in all digits, similar to human brachydactyly type A1, a condition caused by mutations in Indian hedgehog (IHH). We mapped Dsh to chromosome 5 in a region containing Shh and were able to demonstrate an inversion comprising 11.7 Mb. The distal breakpoint is 13.298 kb upstream of Shh, separating the coding sequence from several putative regulatory elements identified by interspecies comparison. The inversion results in almost complete downregulation of Shh expression during E9.5–E12.5, explaining the homozygous phenotype. At E13.5 and E14.5, however, Shh is upregulated in the phalangeal anlagen of Dsh/+ mice, at a time point and in a region where WT Shh is never expressed. The dysregulation of Shh expression causes the local upregulation of hedgehog target genes such as Gli1-3, patched, and Pthlh, as well as the downregulation of Ihh and Gdf5. This results in shortening of the digits through an arrest of chondrocyte differentiation and the disruption of joint development.
Classification of human natural killer cells based on migration behavior and cytotoxic response
Authors: Bruno Vanherberghen, Per E. Olofsson, Elin Forslund, Michal Sternberg-Simon, Mohammad Ali Khorshidi, Simon Pacouret, Karolin Guldevall, Monika Enqvist, Karl-Johan Malmberg, Ramit Mehr, Björn Önfelt
Journal: Blood (2013)
CS-10 * FGFR4 IS EXPRESSED IN HUMAN GLIOMAS OF DIFFERENT GRADES AND HISTOLOGIES
Authors: C. H. Gjerde, E. Mutlu, L. Leiss, P. O. Enger
Journal: Neuro-Oncology (2014)

INTRODUCTION: Fibroblast growth factor receptor (FGFR) 4 is a high-affinity transmembrane receptor for several members of the fibroblast growth factor (FGF) family. FGFR4 is reportedly expressed in several cancer types, including human astrocytomas. However, the expression of FGFR4 across gliomas of different grades and histologies has not been extensively investigated. MATERIALS AND METHODS: We performed immunohistochemistry (IHC) of 170 grade II-IV human gliomas from our tumor bank, including 117 GBMs and 53 lower grade gliomas of astrocytic and oligodendroglial lineage. From the same biopsies we have snap-frozen tissue for qPCR and western blot currently under analysis. RESULTS: So far, IHC has showed that FGFR4 is almost uniformly expressed in human gliomas, although at a varying degree. Microscopy revealed that most tumors stained both in the nuclei as well as in the cytoplasm. We observed both a homogenous and a granular staining pattern of the cytoplasm. In particular transition zone biopsies contained both staining patterns, suggesting involvement of different cell types, possibly from the tumor and stromal cell compartments. Ongoing studies aim at further characterizing the expression of FGFR4 in human gliomas with western blot analysis and real-time quantitative PCR, and will be presented at the conference.
Safety, Pharmacokinetics, and Efficacy of CPX-1 Liposome Injection in Patients with Advanced Solid Tumors
Authors: Gerald Batist, Karen A. Gelmon, Kim N. Chi, Wilson H. Miller, Stephen K.L. Chia, Lawrence D. Mayer, Christine E. Swenson, Andrew S. Janoff, Arthur C. Louie
Journal: Clinical Cancer Research (2009)

Abstract Purpose: CPX-1 is a novel, liposome-encapsulated formulation of irinotecan and floxuridine designed to prolong in vitro optimized synergistic molar ratios of both drugs postinfusion. This open-label, single-arm, dose-escalating phase I study was designed to determine the maximum tolerated dose and pharmacokinetics of CPX-1 in patients with advanced solid tumors. Experimental Design: Patients received CPX-1 at 30, 60, 100, 150, 210, or 270 units/m2 (1 unit = 1 mg irinotecan + 0.36 mg floxuridine) infused over 90 minutes every 14 days in 28-day cycles. Pharmacokinetic samples were collected on days 1 and 15 of cycle 1. Results: Thirty-three patients were enrolled, treated, and evaluated for safety; 30 patients were evaluated for response. A 1:1 plasma irinotecan to floxuridine molar ratio was maintained for 8 to 12 hours. Grade 3/4 toxicities included diarrhea (24.2%), neutropenia (12.1%), and hypokalemia (12.1%); 1 patient (270 units/m2) died of persistent diarrhea, which led to dehydration and renal failure (grade 5). Partial response occurred in 3 (12%) of the 25 subjects evaluated through Response Evaluation Criteria in Solid Tumors. Progression-free survival lasting &amp;gt;6 months occurred in 9 patients, 6 with colorectal cancer. Among 15 colorectal cancer patients (10 with prior irinotecan), the calculated median progression-free survival was 5.4 months; 11 patients (72.7%) achieved disease control and 2 patients (13%) had partial response. Conclusions: Outpatient CPX-1 was well tolerated and antitumor activity was shown in patients with advanced solid tumors. The recommended dose for future studies is 210 units/m2. This is the first clinical evaluation of fixed drug ratio dosing designed to maintain synergistic molar ratios for enhanced therapeutic benefit.
Human hepatic stellate cells show features of antigen-presenting cells and stimulate lymphocyte proliferation
Authors: O Viñas
Journal: Hepatology (2003)

Following cell activation, hepatic stellate cells (HSCs) acquire proinflammatory and profibrogenic properties. We investigated whether activated HSCs also display immune properties. Here we show that cultured human HSCs express membrane proteins involved in antigen presentation, including members of the HLA family (HLA-I and HLA-II), lipid-presenting molecules (CD1b and CD1c), and factors involved in T-cell activation (CD40 and CD80). Exposure of HSCs to proinflammatory cytokines markedly up-regulates these molecules. Importantly, cells freshly isolated from human cirrhotic livers (in vivo activated HSCs) highly express HLA-II and CD40, suggesting that HSCs can act as antigen-presenting cells (APCs) in human fibrogenesis. We also explored whether human HSCs can efficiently process exogenous antigens. Activated HSCs internalize low- and high-molecular-weight dextran and transferrin, indicating that they can perform fluid-phase and receptor-mediated endocytosis. Moreover, HSCs can perform phagocytosis of macromolecules because they internalize latex particles as well as bacteria. Interestingly, both culture-activated and in vivo activated HSCs express high levels of CD68, a protein involved in antigen trafficking. Finally, we studied whether HSCs modulate T-lymphocyte proliferation. In basal conditions, coculture of irradiated HSCs barely induces allogeneic T-lymphocyte proliferation. However, cytokine-stimulated HSCs stimulate the allogeneic T-lymphocyte response in an HLA-II-dependent manner. In conclusion, human activated HSCs express molecules for antigen presentation, internalize macromolecules, and modulate T-lymphocyte proliferation. These results suggest that HSCs may play a role in the immune function of the liver.