tbuckley/cabot-search huggingface dataset:
Human growth hormone doping in sport
Authors: M Saugy, N Robinson, C Saudan, N Baume, L Avois, P Mangin
Journal: British Journal of Sports Medicine (2006)

Background and objectives: Recombinant human growth hormone (rhGH) has been on the list of forbidden substances since availability of its recombinant form improved in the early 1990s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products (androgens, erythropoietin, etc.). The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: the indirect method, which measures a combination of several factors in the biological cascade affected by administration of GH; and the direct method, which measures the difference between the circulating and the recombinant (represented by the unique 22 kD molecule) forms of GH. This article gives an overview of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated. Methods: Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. Results and conclusion: The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed. Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. hGH doping is a major challenge in the fight against doping. The effect of exercise on hGH and its short half-life are still presenting difficulties during doping analysis. To date the most promising method appears to be the direct approach utilising immunoassays.
Response to ‘In erosive hand osteoarthritis more inflammatory signs on ultrasound are found than in the rest of hand osteoarthritis’ by Kortekaas<i>et al</i>
Authors: Ai Lyn Tan, Andrew Grainger, Dennis McGonagle
Journal: Annals of the Rheumatic Diseases (2013)

We read with interest the article ‘In erosive hand osteoarthritis more inflammatory signs on ultrasound are found than in the rest of hand osteoarthritis’ by Kortekaas et al .1 The authors found that interphalangeal joints of erosive osteoarthritis (EOA) patients, with erosions being defined by conventional radiography (CR), demonstrated more sonographic inflammatory changes in adjacent non-CR-eroded joints compared with patients without EOA. This may give the impression that a joint showing erosions on hand CR points towards a more severe generalised inflammatory phenotype and we would like to clarify this.

We are unsure what the significance and robustness of these observations are, given the increasing pathophysiological understanding of hand osteoarthritis that has …
Autoradiographic Analyses of the Cytokinetic Effects of Bleomycin on the Mouse Tumor2
Authors: Jiro Fujimoto
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Autoradiographic Analyses of the Cytokinetic Effects of Bleomycin on the Mouse Tumor Get access Jiro Fujimoto Jiro Fujimoto 3Department of Surgery, Osaka University Medical School, Osaka 553, Japan. 4I thank Dr. G. Kosaki, Dr. H. Higashi, and Dr. S. Takai, Department of Surgery, Osaka University Medical School, for their kind suggestions and encouragement. The labeled bleomycin was a generous gift from Nippon Kayaku Co., Ltd., Tokyo, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Pages 769–774, https://doi.org/10.1093/jnci/63.3.769 Published: 01 September 1979 Article history Received: 24 October 1978 Accepted: 14 March 1979 Published: 01 September 1979
Cell Types, Circuits, and Receptive Fields in the Mouse Visual Cortex
Authors: Cristopher M. Niell
Journal: Annual Review of Neuroscience (2015)

Over the past decade, the mouse has emerged as an important model system for studying cortical function, owing to the advent of powerful tools that can record and manipulate neural activity in intact neural circuits. This advance has been particularly prominent in the visual cortex, where studies in the mouse have begun to bridge the gap between cortical structure and function, allowing investigators to determine the circuits that underlie specific visual computations. This review describes the advances in our understanding of the mouse visual cortex, including neural coding, the role of different cell types, and links between vision and behavior, and discusses how recent findings and new approaches can guide future studies.
Profound Prevention of Experimental Brain Metastases of Breast Cancer by Temozolomide in an MGMT-Dependent Manner
Authors: Diane Palmieri, Renata Duchnowska, Stephan Woditschka, Emily Hua, Yongzhen Qian, Wojciech Biernat, Katarzyna Sosińska-Mielcarek, Brunilde Gril, Andreas M. Stark, Stephen M. Hewitt, David J. Liewehr, Seth M. Steinberg, Jacek Jassem, Patricia S. Steeg
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. Experimental Design: Temozolomide was administered in mice following earlier injection of brain-tropic HER2–positive JIMT-1-BR3 and triple-negative 231-BR-EGFP sublines, the latter with and without expression of O6-methylguanine-DNA methyltransferase (MGMT). In addition, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically. Results: Temozolomide, when dosed at 50, 25, 10, or 5 mg/kg, 5 days per week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing JIMT-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, whereas in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis. Conclusions: Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting. Clin Cancer Res; 20(10); 2727–39. ©2014 AACR.
Disease monitoring in chronic obstructive pulmonary disease: is there a role for biomarkers?
Authors: PL Wielders, PN Dekhuijzen
Journal: European Respiratory Journal (1997)

Biological or biochemical markers (so-called biomarkers) are of potential interest for clinical application to monitor chronic diseases. Although biomarkers are frequently used in toxicology and oncology, their application in monitoring nonmalignant pulmonary disease has been confined to basic research. With the appearance of new noninvasive and less invasive markers it is tempting to speculate on their potential role in patients with chronic obstructive pulmonary disease (COPD).
Abstract 5118: Decursin synergistically enhances TRAIL-induced apoptosis through CHOP dependent DR5 signaling in TRAIL resistant lung cancer cells
Authors: Kim Jae Kwang
Journal: Cancer Research (2014)

Abstract Targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which has been clinically established for anticancer therapy, is the attractive strategy to specifically kill cancer cells through the death receptors. Nonetheless, its therapeutic potential is limited due to the resistance in cancer cells. Thus, in the present study, we evaluated the therapeutic potential of Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root as a TRAIL sensitizer in a variety of resistant lung cancer cells. Co-treatment of Decursin with TRAIL synergistically induced apoptosis in TRAIL resistant lung cancer cells, A545, H1299, H596 and Calu-1. This synergistic effect through the induction of DR5 in Decursin treated cells was also confirmed by immunoblotting and immunoanalysis of endogeneous and surface expression of DR5, respectively. In contrast, in DR knockdown cells, combination treatment Decursin and TRAIL did not induce apoptosis at all. Furthermore, we found that DR5 induction by Decursin was mediated by ER-stress and its byproduct CHOP. Depletion of CHOP via siRNA transfection completely blocked Decusin induced apoptosis cell death in TRAIL resistant lung cancer cells. Taken together, induction of the DR5 via upregulation of CHOP and its inducer, ER stress, by Decursin leads to synergistically increase the TRAIL mediated cell death in TRAIL resistant lung cancer cells. Our results indicate that Decursin is a useful therapeutic strategy for overcoming TRAIL resistance in lung tumor treatment. Key words: Decursin, DR-5, ER stress, CHOP, Trail resistant, Lung cancer Conflict of Interests: The authors disclose no potential conflicts of interest. Acknowledgment: This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MEST) (no. 2012-0005755). Citation Format: Kim Jae Kwang. Decursin synergistically enhances TRAIL-induced apoptosis through CHOP dependent DR5 signaling in TRAIL resistant lung cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5118. doi:10.1158/1538-7445.AM2014-5118
An Approach to Alcoholism in a University Medical Center Complex
Authors: W. Anderson Spickard
Journal: JAMA (1984)

We developed a three-part approach to the problem of alcoholism among the employees and faculty of the Vanderbilt University and Medical Center. This included identification of faculty and staff with problem drinking, guidance of those identified for rehabilitation, and an educational program for students. Forty university employees (37 staff and three faculty) with problem drinking were identified and referred for rehabilitation. The principles of employee assistance used successfully in industry were applied in this employee group. The 65% "job rehabilitation" rate is comparable with that achieved in industrial employee assistance programs. Identification and rehabilitation of faculty in the university required special approaches. The educational program for students as part of the medical school elective curriculum was attended by most of the first- and second-year medical students.
Spontaneous production of transforming growth factor-beta 2 by primary cultures of bronchial epithelial cells. Effects on cell behavior in vitro.
Authors: O Sacco, D Romberger, A Rizzino, J D Beckmann, S I Rennard, J R Spurzem
Journal: Journal of Clinical Investigation (1992)

The ability of airway epithelial cells to produce transforming growth factor-beta (TGF-beta) may be an important mechanism for the control of growth, differentiation, and repair of the airway epithelium. To determine whether airway epithelial cells are capable of producing TGF-beta, we examined primary cultures of bovine bronchial epithelial cells. Using a bioassay, TGF-beta activity was detected readily in media conditioned by bovine bronchial epithelial cells. Neutralizing antisera to TGF-beta 1 and TGF-beta 2 were used to demonstrate that the majority of the activity was of the TGF-beta 2 isoform. Interestingly, some of the TGF-beta activity was present in the conditioned media as "active" TGF-beta, not requiring acid activation. The production of TGF-beta was variable, depending on cell density and the presence of retinoic acid. The presence of endogenously produced active TGF-beta in the culture media was shown to modulate the behavior of the cell cultures as evidenced by the effects of TGF-beta-neutralizing antisera on cell size and fibronectin production. Our results suggest that active TGF-beta produced by airway epithelial cells may function in an autocrine or paracrine manner to modulate epithelial cell behavior.
Siah Proteins: Novel Drug Targets in the Ras and Hypoxia Pathways
Authors: Colin M. House, Andreas Möller, David D.L. Bowtell
Journal: Cancer Research (2009)

Abstract The Siah (seven in absentia homolog) family of RING-domain proteins are components of ubiquitin ligase complexes, targeting proteins for proteasomal degradation. Siah family members have been reported to function in Ras, estrogen, DNA-damage, and hypoxia response pathways. Although earlier reports implicated Siah proteins as tumor suppressors, recent studies in mouse models have shown that Siah inhibition impairs tumor growth and metastasis. Given their central role in oncogenic and angiogenic pathways, Siah proteins are attractive novel therapeutic targets in cancer. [Cancer Res 2009;69(23):8835–8]
Crohn's disease and myasthenia gravis: a possible role for thymectomy.
Authors: I A Finnie, R Shields, R Sutton, R Donnelly, A I Morris
Journal: Gut (1994)

A female patient with a three year history of Crohn's disease of the colon developed myasthenia gravis. Despite diversion of the faecal stream by an ileostomy, and total colectomy, the patient had continuing problems with perineal and perianal abscesses and fistulas. Her myasthenia gravis became unresponsive to anti-cholinergics so a thymectomy was performed. The perineal and perianal disease improved subsequently. This case supports the theory that functional disturbances of the thymus may have a role in the pathogenesis of inflammatory bowel disease.
The predominance of hepatitis delta virus genotype I among chronically infected Italian patients
Authors: G A Niro, A Smedile, A Andriulli, M Rizzetto, J L Gerin, J L Casey
Journal: Hepatology (1997)

The sera of 46 Italian patients with chronic hepatitis delta virus (HDV) infection were analyzed for HDV RNA by polymerase chain reaction (PCR) amplification. Genetic analysis of sequences amplified from two regions of the HDV genome indicated that all HDV RNA-positive patients (98%) were infected with HDV genotype I. In Italy, infection with this genotype appeared to be associated with a broad spectrum of chronic disease. No subtypes of HDV genotype I were identified, nor were genetic variations clearly associated with different disease patterns; however, clustering of some sequences suggested correlations with geography and transmission route. Italian HDV genotype I sequences were more diverse than those from east Asia and North America, suggesting that HDV genotype I was likely introduced to Italy earlier and/or from multiple sources as compared to those areas. All sequences analyzed were predicted to fold into the unbranched rod structure typical of HDV RNA. Within this structure, three conserved features were identified, including sequences around the RNA editing site and the polyadenylation signal site. We conclude that in Italy, where HDV infection has been endemic, the overwhelmingly predominant genotype of HDV is genotype I.
The Activity of Trabectedin As a Single Agent or in Combination with Everolimus for Clear Cell Carcinoma of the Ovary
Authors: Seiji Mabuchi, Takeshi Hisamatsu, Chiaki Kawase, Masami Hayashi, Kenjiro Sawada, Kazuya Mimura, Kazuhiro Takahashi, Toshifumi Takahashi, Hirohisa Kurachi, Tadashi Kimura
Journal: Clinical Cancer Research (2011)

The objective of this study was to evaluate the antitumor efficacy of trabectedin in clear cell carcinoma (CCC) of the ovary, which is regarded as an aggressive, chemoresistant, histologic subtype.Using 6 human ovarian cancer cell lines (3 CCC and 3 serous adenocarcinomas), the antitumor effects of trabectedin were examined in vitro, and we compared its activity according to histology. We next examined the antitumor activity of trabectedin in both cisplatin-resistant and paclitaxel-resistant CCC cells in vitro. Then, the in vivo effects of trabectedin were evaluated using mice inoculated with CCC cell lines. Using 2 pairs of trabectedin-sensitive parental and trabectedin-resistant CCC sublines, we investigated the role of mTOR in the mechanism of acquired resistance to trabectedin. Finally, we determined the effect of mTOR inhibition by everolimus on the antitumor efficacy of trabectedin in vitro and in vivo.Trabectedin showed significant antitumor activity toward chemosensitive and chemoresistant CCC cells in vitro. Mouse xenografts of CCC cells revealed that trabectedin significantly inhibits tumor growth. Greater activation of mTOR was observed in trabectedin-resistant CCC cells than in their respective parental cells. The continuous inhibition of mTOR significantly enhanced the therapeutic efficacy of trabectedin and prevented CCC cells from acquiring resistance to trabectedin.Trabectedin is a promising agent for CCC as a first-line chemotherapy and as a second-line treatment of recurrent CCC that had previously been treated with cisplatin or paclitaxel. Moreover, trabectedin combined with everolimus may be more efficacious for the management of CCC.
Prostate Cancer Associated with <i>p53</i> and <i>Rb</i> Deficiency Arises from the Stem/Progenitor Cell–Enriched Proximal Region of Prostatic Ducts
Authors: Zongxiang Zhou, Andrea Flesken-Nikitin, Alexander Yu. Nikitin
Journal: Cancer Research (2007)

Recently, we have shown that prostate epithelium-specific deficiency for p53 and Rb tumor suppressors leads to metastatic cancer, exhibiting features of both luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of carcinogenesis in this model, we report that all malignant neoplasms arise from the proximal region of the prostatic ducts, the compartment highly enriched for prostatic stem/progenitor cells. In close similarity to reported properties of prostatic stem cells, the cells of the earliest neoplastic lesions express stem cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal. Like a subset of normal cells located in the proximal region of prostatic ducts, the early neoplastic cells coexpress luminal epithelium markers cytokeratin 8, androgen receptor, and neuroendocrine markers synaptophysin and chromogranin A. Inactivation of p53 and Rb also takes place in the lineage-committed transit-amplifying and/or differentiated cells of the distal region of the prostatic ducts. However, the resulting prostatic intraepithelial neoplasms never progress to carcinoma by the time of mouse death. Interestingly, in an ectopic transplantation assay, early mutant cells derived from either region of the prostatic ducts are capable of forming neoplasms within 3 months. These findings indicate that p53 and Rb are critically important for the regulation of the prostatic stem cell compartment, the transformation in which may lead to particularly aggressive cancers in the context of microenvironment.
Cediranib for Metastatic Alveolar Soft Part Sarcoma
Authors: Shivaani Kummar, Deborah Allen, Anne Monks, Eric C. Polley, Curtis D. Hose, S. Percy Ivy, Ismail B. Turkbey, Scott Lawrence, Robert J. Kinders, Peter Choyke, Richard Simon, Seth M. Steinberg, James H. Doroshow, Lee Helman
Journal: Journal of Clinical Oncology (2013)

Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs).
Cardiac Arrest in Hypothermia
Authors: J. Douglas White
Journal: JAMA (1980)

<h3>To the Editor.—</h3> While I applaud the admonitions of Southwick and Daglish (243:1250, 1980) to pursue resuscitation in profoundly hypothermic patients with asystole, I cannot agree with their suggestion that ventricular fibrillation is somehow a consequence or complication of the resuscitation process. Moreover, the authors imply that bradyarrhythmias are benign and associated with a favorable prognosis, and our experience is not compatible with this belief. We have recently completed a prospective study on the subject of hypothermia at the Bellevue Hospital Medical Center. Among 102 patients seen over a calendar year with core temperatures less than 35 °C, we discerned a group of patients (those with core temperatures less than 26 °C) with a considerably worse prognosis, primarily as the result of refractory ventricular arrhythmias and spontaneous cardiac arrest. Eleven patients had such profound hypothermia, and in four of these, refractory ventricular fibrillation occurred. These patients had no underlying medical disease
Nested N-Terminal Megalin Fragments Induce High-Titer Autoantibody and Attenuated Heymann Nephritis
Authors: Alfonso Tramontano, Thomas Knight, Domenica Vizzuso, Sudesh P. Makker
Journal: Journal of the American Society of Nephrology (2006)

It was shown previously that an N-terminal fragment (nM60) that encompasses amino acid residues 1 to 563 of megalin could induce active Heymann nephritis (AHN) as efficiently as the native protein. For delineation of a minimal structure within this fragment that is sufficient to induce AHN, smaller protein fragments that encompass residues 1 to 236 (L6), 1 to 195 (L5), 1 to 156 (L4), and 1 to 120 (L3), representing successive C-terminal truncations within ligand-binding repeats of nM60, were cloned and produced in a baculovirus insect cell expression system. Protein fragments L4, L5, and L6 clearly were glycosylated. All four fragments stimulated proliferation of megalin-sensitized lymph node cells and induced high-titer anti-megalin autoantibodies in Lewis rats. A full-blown disease, as assessed by severity of proteinuria, was observed in rats that were immunized with L6 and L5, whereas animals that were immunized with L4 and L3 developed only mild disease. The proteinuria levels correlated with staining for complement (C3, C5b-9) and IgG1 isotype in glomerular immune deposits. The results suggest that one or more molecular determinants on the region that comprises amino acid residues 157 to 236 contribute to the induction of a full-blown form of AHN. Study of the structure, conformation, and posttranslational modifications of these determinants could provide greater insight into the molecular correlates of immunopathogenesis in this disease model.
Acetylcholine may be an autocrine growth factor for lung cancer
Authors: A De-Soyza
Journal: Thorax (2003)

▴ Song P, Sekhon HS, Proskocil B, et al . Synthesis of acetylcholine by lung cancer. Life Sci2003;72:2159–68 [OpenUrl][1][CrossRef][2][PubMed][3] Researchers have recently shown that small cell lung cancer (SCLC) cell lines secrete acetylcholine (ACh) into tissue culture medium. Treatment of the cell lines in vitro with either muscarinic (atropine) or … [1]: {openurl}?query=rft.jtitle%253DLife%2Bsciences%26rft.stitle%253DLife%2BSci%26rft.aulast%253DSong%26rft.auinit1%253DP.%26rft.volume%253D72%26rft.issue%253D18-19%26rft.spage%253D2159%26rft.epage%253D2168%26rft.atitle%253DSynthesis%2Bof%2Bacetylcholine%2Bby%2Blung%2Bcancer.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0024-3205%252803%252900078-X%26rft_id%253Dinfo%253Apmid%252F12628474%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0024-3205(03)00078-X&link_type=DOI [3]: /lookup/external-ref?access_num=12628474&link_type=MED&atom=%2Fthoraxjnl%2F58%2F7%2F597.atom