tbuckley/cabot-search huggingface dataset:
Water Potentiates the Pressor Effect of Ephedra Alkaloids
Authors: Jens Jordan, John R. Shannon, André Diedrich, Bonnie Black, David Robertson, Italo Biaggioni
Journal: Circulation (2004)

The use of ephedra alkaloids in over-the-counter preparations has been associated with potentially serious cerebrovascular events. Because of its potential association with hemorrhagic strokes, phenylpropanolamine has been largely substituted for by pseudoephedrine, but it is not clear whether this is indeed a safer alternative. It would be important to understand the cardiovascular effects of ephedra alkaloids, but these are normally masked by baroreflex buffering mechanisms. We therefore investigated the effects of ephedra alkaloids in patients with autonomic impairment and explored their potential interaction with water ingestion.The cardiovascular effects of phenylpropanolamine or pseudoephedrine, alone and in combination with water, were determined in 13 subjects with impairment of baroreflex function due to autonomic failure. Phenylpropanolamine, 12.5 to 25 mg PO, increased systolic blood pressure (SBP) by 21+/-14 mm Hg after 90 minutes. However, when ingested with 16 oz of room temperature tap water, phenylpropanolamine increased SBP by 82+/-2 mm Hg. Pseudoephedrine, 30 mg PO, increased SBP on average 52+/-9 mm Hg when taken with 16 oz of water and by as much as 88 mm Hg.Ephedra alkaloids increase blood pressure significantly in individuals with impaired baroreflex function. Concomitant ingestion of ephedra alkaloids and water produced a greater increase in blood pressure. If used cautiously, this interaction can be beneficial in the treatment of orthostatic hypotension. On the other hand, it could contribute to the cardiovascular complications associated with the use of ephedra alkaloids, given that baroreflex function varies widely in normal individuals and is impaired in several medical conditions.
Analysis of the cues used by patients when making assessments of their asthma severity
Authors: E. A. Barley, P. W. Jones
Journal: European Respiratory Journal (2005)

This study measured the relative contribution of four cues: symptoms, effect on activities, emotions and social life, to patients' judgments of overall asthma severity. Judgement analysis techniques were applied to patients' assessments of overall asthma severity using asthma states described in scenarios based on these cues. Altogether, 40 patients, mean age 52 yrs, mean forced expiratory volume in one second 67% predicted, were studied. The relative importance of the cues varied widely between patients; symptoms contributed to 47% of the judgment of asthma severity (range 15–86%), activities 19% (1–73%), emotions 14% (0–43%), and social life 19% (2–57%). Some patients had difficulty with the judgment task, they tended to be older or have worse health. A total of 21 patients had consistent judgment policies. Cluster analysis identified two policy types. In one, symptoms were weighted heavily, in the other all cues were weighted similarly. Policies were not related to disease or demographic factors. Symptoms are important cues for patients when assessing asthma severity, but other cues may be more important in some patients. Patients fall into two groups: those who rely on symptoms and those who use several cues.
Drug–drug interactions in patients treated for cancer: a prospective study on clinical interventions
Authors: R.W.F. van Leeuwen, F.G.A. Jansman, P.M.L.A. van den Bemt, F. de Man, F. Piran, I. Vincenten, A. Jager, A.W. Rijneveld, J.D. Brugma, R.H.J. Mathijssen, T. van Gelder
Journal: Annals of Oncology (2015)
Protein-Bound Uremic Toxins Induce Tissue Remodeling by Targeting the EGF Receptor
Authors: Chiao-Yin Sun, Guang-Huar Young, Yu-Ting Hsieh, Yau-Hung Chen, Mai-Szu Wu, Vin-Cent Wu, Jia-Hung Lee, Chin-Chan Lee
Journal: Journal of the American Society of Nephrology (2014)

Indoxyl sulfate and p-cresol sulfate have been suggested to induce kidney tissue remodeling. This study aimed to clarify the molecular mechanisms underlying this tissue remodeling using cultured human proximal renal tubular cells and half-nephrectomized mice treated with indoxyl sulfate or p-cresol sulfate as study models. Molecular docking results suggested that indoxyl sulfate and p-cresol sulfate dock on a putative interdomain pocket of the extracellular EGF receptor. In vitro spectrophotometric analysis revealed that the presence of a synthetic EGF receptor peptide significantly decreased the spectrophotometric absorption of indoxyl sulfate and p-cresol sulfate. In cultured cells, indoxyl sulfate and p-cresol sulfate activated the EGF receptor and downstream signaling by enhancing receptor dimerization, and increased expression of matrix metalloproteinases 2 and 9 in an EGF receptor-dependent manner. Treatment of mice with indoxyl sulfate or p-cresol sulfate significantly activated the renal EGF receptor and increased the tubulointerstitial expression of matrix metalloproteinases 2 and 9. In conclusion, indoxyl sulfate and p-cresol sulfate may induce kidney tissue remodeling through direct binding and activation of the renal EGF receptor.
Sexual precocity and recurrent β-human chorionic gonadotropin upsurges preceding the diagnosis of a malignant mediastinal germ-cell tumor in a 9-year-old boy
Authors: J. Schwabe, G. Calaminus, W. Vorhoff, V. Engelbrecht, B.P. Hauffa, U. Göbel
Journal: Annals of Oncology (2002)
Randomised controlled trial of efficacy of albendazole in intra-abdominal hydatid disease
Authors: L.A. Gil-Grande, J.J. Sánchez-Ruano, F. García-Hoz, R. Bárcena, F. Rodriguez-Caabeiro, C. Brasa, N. Casado, J.G. Prieto, A.I. Alvarez, L. Aguilar, R. Dal-Ré
Journal: The Lancet (1993)
Drug transporter regulation in tumors by DNA methylation
Authors: Oliver Zolk, Martin F Fromm
Journal: Genome Medicine (2012)

Epigenetic alterations, such as aberrant DNA methylation, are a hallmark of cancer. DNA hypermethylation of the promoter region affects, for example, the expression of tumor suppressor genes and is associated with their transcriptional silencing in tumors. A recent report has provided evidence for epigenetic silencing of the multispecific organic cation transporter SLC22A1 in hepatocellular carcinoma. Given the role of this transporter in the cellular uptake of several anticancer drugs, the study provided a novel mechanism to explain the substantial variability in treatment response, and it might provide a new strategy for optimization of pharmacotherapy of hepatocellular carcinoma. See research article http://www.genomemedicine.com/content/3/12/82
Addition of Epirubicin As a Third Drug to Carboplatin-Paclitaxel in First-Line Treatment of Advanced Ovarian Cancer: A Prospectively Randomized Gynecologic Cancer Intergroup Trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens
Authors: Andreas du Bois, Beatrice Weber, Justine Rochon, Werner Meier, Alain Goupil, Sigrid Olbricht, Jean-Claude Barats, Walther Kuhn, Hubert Orfeuvre, Uwe Wagner, Barbara Richter, Hans-Joachim Lueck, Jacobus Pfisterer, Serban Costa, Willibald Schroeder, Rainer Kimmig, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2006)

Despite the progress that has been achieved, long-term survival rates in patients with advanced ovarian cancer are still disappointing. One attempt to improve results could be the addition of non-cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines were among the candidates for incorporation as a third drug into first-line regimens.We performed a prospectively randomized phase III study comparing carboplatin-paclitaxel (TC; area under the curve 5/175 mg/m2, respectively) with epirubicin 60 mg/m2 added to the same combination (TEC) in previously untreated patients with advanced epithelial ovarian cancer. All drugs were administered intravenously on day 1 of a 3-week schedule for a planned minimum of six courses.Between November 1997 and February 2000, 1,282 patients were randomly assigned to receive either TC (635 patients) or TEC (647 patients), respectively. Grade 3/4 hematologic and some nonhematologic toxicities (nausea/emesis, mucositis, and infections) occurred significantly more frequently in the TEC arm. Accordingly, quality-of-life analysis showed inferiority of TEC versus TC. Median progression-free survival time was 18.4 months for the TEC arm and 17.9 months for the TC arm (hazard ratio [HR], 0.95; 95% CI, 0.83 to 1.07; P = .3342). Median overall survival time was 45.8 months for the TEC arm and 41.0 months for the TC arm (HR, 0.93; 95% CI, 0.81 to 1.08; P = .3652). Similar nonsignificant differences were observed when strata were analyzed separately.Addition of epirubicin to TC did not improve survival or time to treatment failure in patients with advanced epithelial ovarian cancer; therefore, it cannot be recommended for clinical use in this population.
Colony-Stimulating Factor-1 Signaling Suppresses Renal Crystal Formation
Authors: Kazumi Taguchi, Atsushi Okada, Hiroshi Kitamura, Takahiro Yasui, Taku Naiki, Shuzo Hamamoto, Ryosuke Ando, Kentaro Mizuno, Noriyasu Kawai, Keiichi Tozawa, Kenichi Asano, Masato Tanaka, Ichiro Miyoshi, Kenjiro Kohri
Journal: Journal of the American Society of Nephrology (2014)

We recently reported evidence suggesting that migrating macrophages (Mϕs) eliminate renal crystals in hyperoxaluric mice. Mϕs can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2Mϕ phenotype. M2Mϕs promote renal tissue repair and regeneration, but it is not clear whether these cells are involved in suppressing renal crystal formation. We investigated the role of M2Mϕs in renal crystal formation during hyperoxaluria using CSF-1–deficient mice, which lack M2Mϕs. Compared with wild-type mice, CSF-1–deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1–deficient and wild-type mice. Flow cytometry of sorted renal Mϕs showed that CSF-1 deficiency resulted in a smaller population of CD11b+F4/80+CD163+CD206hi cells, which represent M2-like Mϕs. Additionally, transfusion of M2Mϕs into CSF-1–deficient mice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized Mϕs than M1-polarized Mϕs or renal tubular cells. Gene array profiling showed that CSF-1 deficiency resulted in disordered M2- and stone-related gene expressions. Collectively, our results provide compelling evidence for a suppressive role of CSF-1 signaling in renal crystal formation.
Prime Time
Authors: Renee E. Sieving, Annie-Laurie McRee, Barbara J. McMorris, Kara J. Beckman, Sandra L. Pettingell, Linda H. Bearinger, Ann W. Garwick, Jennifer A. Oliphant, Shari Plowman, Michael D. Resnick, Molly Secor-Turner
Journal: JAMA Pediatrics (2013)

Preventing early pregnancy among vulnerable adolescents requires innovative and sustained approaches. Prime Time, a youth development intervention, aims to reduce pregnancy risk among adolescent girls seeking clinic services who are at high risk for pregnancy.To evaluate sexual risk behaviors and related outcomes with a 24-month postbaseline survey, 6 months after the conclusion of the Prime Time intervention.Randomized controlled trial.Community and school-based primary care clinics.Of 253 sexually active 13- to 17-year-old girls meeting specified risk criteria, 236 (93.3%) completed the 24-month follow-up survey.Offered during an 18-month period, Prime Time includes case management and youth leadership programs.Self-reported consistency of condom, hormonal, and dual-method contraceptive use with most recent male sex partner and number of male sex partners in the past 6 months.At 24-month follow-up, the intervention group reported significantly more consistent use of condoms, hormonal contraception, and dual-method contraception than the control group. Intervention participants also reported improvements in family connectedness and self-efficacy to refuse unwanted sex, and reductions in the perceived importance of having sex. No between-group differences were found in the number of recent male sex partners.This study contributes to what has been a dearth of evidence regarding youth development interventions offered through clinic settings, where access to high-risk adolescents is plentiful but few efforts have emphasized a dual approach of strengthening sexual and nonsexual protective factors while addressing risk. Findings suggest that health services grounded in a youth development framework can lead to long-term reductions in sexual risk among vulnerable youth.
Apoptotic Protease Activating Factor 1 (Apaf-1)–Independent Cell Death Suppression by Bcl-2
Authors: Misako Haraguchi, Seiji Torii, Shu-ichi Matsuzawa, Zhihua Xie, Shinichi Kitada, Stanislaw Krajewski, Hiroki Yoshida, Tak W. Mak, John C. Reed
Journal: The Journal of Experimental Medicine (2000)

Reportedly, antiapoptotic Bcl-2 family proteins suppress apoptosis by binding to and inhibiting members of the CED-4 family of caspase activators. To explore this question, we used embryonic stem (ES) cells in which one (−/+) or both (−/−) copies of the gene encoding apoptotic protease activating factor 1 (Apaf-1), a CED-4 homologue, were disrupted by homologous recombination. Stable clones of heterozygous (−/+) and homozygous (−/−) Apaf-1 knockout ES cells that overexpressed Bcl-2 were generated. Withdrawal of serum growth factors or stimulation of heterozygous ES cells with staurosporine (STS), ultraviolet (UV)B irradiation, etoposide (VP16), or cisplatin induced apoptosis followed by cell death (determined by failure to exclude propidium iodide dye). These cell death stimuli also induced activation of several types of caspases and loss of mitochondrial membrane potential (ΔΨ) in heterozygous (+/−) Apaf-1 knockout ES cells. In addition, overexpression of Bcl-2 protected against these events in Apaf-1–expressing ES cells. In contrast, STS, UVB, and VP16 induced little or no caspase activation and apoptosis in homozygous (−/−) Apaf-1 knockout ES cells. Nevertheless, Apaf-1–deficient ES cells subjected to these cell death stimuli or deprived of growth factors did eventually die through a nonapoptotic mechanism associated with loss of ΔΨ. Moreover, Bcl-2 overprotection preserved ΔΨ, reduced the percentage of Apaf-1−/− ES cells undergoing cell death, and increased clonigenic survival. The extent of Bcl-2–mediated cytoprotection was not significantly different for heterozygous (−/+) versus homozygous (−/−) Apaf-1 knockout cells. Furthermore, although Bcl-2 could be readily coimmunoprecipitated with Bax, associations with Apaf-1 were undetectable under conditions where Apaf-1 interactions with procaspase-9 were observed. We conclude that Bcl-2 has cytoprotective functions independent of Apaf-1, preserving mitochondrial function through a caspase-independent mechanism.
Estrogen directly activates AID transcription and function
Authors: Siim Pauklin, Isora V. Sernández, Gudrun Bachmann, Almudena R. Ramiro, Svend K. Petersen-Mahrt
Journal: The Journal of Experimental Medicine (2009)

The immunological targets of estrogen at the molecular, humoral, and cellular level have been well documented, as has estrogen's role in establishing a gender bias in autoimmunity and cancer. During a healthy immune response, activation-induced deaminase (AID) deaminates cytosines at immunoglobulin (Ig) loci, initiating somatic hypermutation (SHM) and class switch recombination (CSR). Protein levels of nuclear AID are tightly controlled, as unregulated expression can lead to alterations in the immune response. Furthermore, hyperactivation of AID outside the immune system leads to oncogenesis. Here, we demonstrate that the estrogen–estrogen receptor complex binds to the AID promoter, enhancing AID messenger RNA expression, leading to a direct increase in AID protein production and alterations in SHM and CSR at the Ig locus. Enhanced translocations of the c-myc oncogene showed that the genotoxicity of estrogen via AID production was not limited to the Ig locus. Outside of the immune system (e.g., breast and ovaries), estrogen induced AID expression by &amp;gt;20-fold. The estrogen response was also partially conserved within the DNA deaminase family (APOBEC3B, -3F, and -3G), and could be inhibited by tamoxifen, an estrogen antagonist. We therefore suggest that estrogen-induced autoimmunity and oncogenesis may be derived through AID-dependent DNA instability.
CD19 has a potential CD77 (globotriaosyl ceramide)-binding site with sequence similarity to verotoxin B-subunits: implications of molecular mimicry for B cell adhesion and enterohemorrhagic Escherichia coli pathogenesis.
Authors: M D Maloney, C A Lingwood
Journal: The Journal of Experimental Medicine (1994)

The glycosphingolipid globotriaosyl ceramide (CD77) and other globo-series glycolipids containing terminal galactose (Gal)alpha 1-4Gal residues function as receptors for the verotoxin (Shiga-like toxin) family of Escherichia coli-elaborated toxins. CD77 is also a marker for germinal center B lymphocytes and Burkitt's lymphoma cells. The pan B cell marker CD19 is a 95-kD membrane protein that appears early in B cell differentiation and is only lost upon terminal differentiation to plasma cells. CD19 is involved in signal transduction and has a regulatory role in B cell proliferation and differentiation in response to activation in vitro. However, an endogenous ligand for CD19 has not yet been identified. We report herein that the extracellular domain of CD19 has a potential CD77-binding site with extensive sequence similarity to the verotoxin B-subunits. These B-subunit-like sequences on CD19 are in close proximity following the organization of intervening amino acids into disulfide-linked domains. Cocapping of CD19 and CD77 on Burkitt's lymphoma-derived Daudi cells with anti-CD19 antibodies indicates that CD19 and CD77 are associated on the B cell surface. Cell surface binding of anti-CD19 antibodies is decreased on CD77-deficient mutant Daudi cells, suggesting that CD77 expression influences the surface expression of CD19. Wild-type Daudi cells, but not the CD19/CD77-deficient mutants, bind to matrices expressing the carbohydrate moiety of CD77 or other Gal alpha 1-4Gal containing glycolipids. This binding can be inhibited by anti-CD77 antibodies, the CD77-binding verotoxin B-subunit or anti-CD19 antibodies. Daudi cells exhibit a degree of spontaneous homotypic adhesion in culture while the CD77/CD19-deficient Daudi mutants grow as single cells. The stronger homotypic adhesion that occurs in B cells after antibody ligation of CD19 and that involves, to some extent, the integrin system, is also dramatically lower in the mutant cells relative to the parent cell line. However, reconstitution of mutant cells with CD77 restores the anti-CD19 mAb-induced adhesion to wild-type Daudi cell levels. These studies represent the first time that CD19-mediated signaling has been reconstituted in a low-responder B cell line. These convergent observations provide compelling evidence that CD19/CD77 interactions function in adhesion and signal transduction at a specific stage in B cell development and suggest that such interactions have a role in B lymphocyte homing and germinal center formation in vivo. By targeting CD77+ B cells, verotoxins may suppress the humoral arm of the immune response during infection.(ABSTRACT TRUNCATED AT 400 WORDS)
Standardisation of lung function testing: helpful guidance from the ATS/ERS Task Force
Authors: G Laszlo
Journal: Thorax (2006)

A critical overview of the new ATS/ERS guidelines

The American Thoracic Society and the European Respiratory Society have jointly issued a new revision of their guidelines for the performance of spirometry, lung volumes, and carbon monoxide transfer factor. These have been published as a series of documents in the European Respiratory Journal .1–5 They contain much wisdom, some compromises, and a few new recommendations. Blood gases, sleep, exercise, and challenge testing have not yet been readdressed. This brief review highlights a few of the more important recommendations dealing with the performance and interpretation of the several tests.

This first chapter is essential reading for laboratory staff and sets standards for hygiene, calibration, quality control, and housekeeping. Observance of these standards will reassure research workers as well as clinicians.

Peak flow is the topic of current research and the task force plans to introduce more stringent standards for home recording. It may be derived from the flow-volume plot or from a separate blow, ideally using a flow measuring device. The guideline emphasises the importance of rehearsal and the need to blow immediately after a full inspiration.

Relaxed expired and inspired vital capacity (EVC and IVC) have been rehabilitated, in spite of the fact that the various COPD guidelines—such as GOLD and others—chose to dispense with them for simplicity. When performing spirometry, the suggested method for EVC is to take the best of three measurements made before the forced expiratory tests, instructing the patient to speed the expiration only at the beginning and end of the blow. There is still no validated standard patter for this test; one suggestion might be “take a full breath in; breathe out gently but firmly”, going on to further encouragement after 2–3 seconds until flow is less than 0.25 l/s.

For forced vital capacity …
Initial myocardial adjustments to brief periods of ischemia and reperfusion in the conscious dog.
Authors: M Pagani, S F Vatner, H Baig, E Braunwald
Journal: Circulation Research (1978)

The changes in left ventricular (LV) dynamics induced by brief periods of ischemia (100 seconds) and subsequent reperfusion were analyzed in conscious dogs. Global LV ischemia, induced by partially occluding the left main coronary artery, reduced LV flow homogeneously and impaired LV function as reflected by decreases in LV stroke "work" (89 +/- 4% M +/- SE), systolic shortening (72 +/- 4%), velocity of shortening (56 +/- 6%), LV systolic pressure (34 +/- 5%), and dP/dt (59 +/- 6%). Regional LV ischemia, induced by occluding either the left circumflex or anterior descending coronary artery completely, reduced flow to the ischemic segment (82 +/- 3%) while decreasing segment work (96 +/- 5%), shortening (82 +/- 3%), and velocity of shortening (70 +/- 5%), with minimal depression of overall LV function. In both groups the extent of shortening was reduced more rapidly and greater (P less than 0.01) than shortening velocity. Moreover, with localized ischemia, segment work was reduced more (P less than 0.01) than shortening. With reperfusion, a transient overshoot in function above preischemic control levels was observed in both groups (global work increased by 60 +/- 12% and regional work by 28 +/- 4% above control). This overshoot was not dependent on adrenergic mechanisms, but was prevented by inhibiting reactive hyperemia. Thus myocardial ischemia induces a dissociation between extent and rate of myocardial shortening. A further dissociation between shortening and work is apparent with regional ischemia. After reperfusion there is a transient overshoot in function which appears to be dependent upon the associated reactive hyperemia.