tbuckley/cabot-search huggingface dataset:
Production of bone-resorbing activity and colony-stimulating activity in vivo and in vitro by a human squamous cell carcinoma associated with hypercalcemia and leukocytosis.
Authors: K Sato, H Mimura, D C Han, T Kakiuchi, Y Ueyama, H Ohkawa, T Okabe, Y Kondo, N Ohsawa, T Tsushima
Journal: Journal of Clinical Investigation (1986)

A squamous cell carcinoma of 33-yr-old patient who developed marked leukocytosis and hypercalcemia was transplanted into nude mice in which more marked leukocytosis and hypercalcemia also developed. This tumor (LJC-1-JCK) produced a colony-stimulating factor (CSF) and formed a cyst in the tumor from which a CSF-producing cell line (T3M-1) was established. The CSF causes predominantly formation of granulocytic colonies in addition to macrophage colonies. Bone-resorbing activity (BRA) was detected in the cystic fluid and was eluted as two separate peaks with proteins of an apparent molecular weight of 30,000-50,000 and 10,000-20,000. Colony-stimulating activity (CSA) was eluted at an apparent 30,000 mol wt. The conditioned medium of the T3M-1 cells also contained a BRA with an apparent 14,000 mol wt, whereas CSA eluted at an apparent 30,000 mol wt. PTH, epidermal growth factor, transforming growth factor-alpha, prostaglandin Es, and vitamin D could not account for the powerful BRA. In contrast to CSA, BRA was not inactivated by trypsin and more stable at 70 degrees C. When T3M-1 cells were transplanted into nude mice, marked hypercalcemia developed in addition to granulocytosis. Our findings suggest that the tumor produces and secretes a powerful BRA in vivo and in vitro, which is different from CSA in terms of molecular weight, heat stability, and trypsin treatment. We speculate that the synergistic action of CSF that stimulates macrophage colony formation and recruits osteoclast precursors, and BRA, which stimulates mononuclear phagocytes and/or osteoclasts were responsible for a marked increase in osteoclastic bone resorption and humoral hypercalcemia in the patient.
CONDUCT DISORDERS OF CHILDREN
Authors: IRA S. WILE
Journal: JAMA (1927)

Conduct is defined as the way in which a person acts or lives; the doings or deeds of a person collectively considered. Behavior is conduct in its external relations to life. There is inherent in the term conduct the idea of personality and moral responsibility. Conduct is an energy phenomenon. It is dynamic and is the sum total of the reactions of an organism in and through living. Not all the elements of conduct are visible at any one time. It floats on the sea of life like an iceberg, with the greatest bulk and the most dangerous portions of it submerged below the surface. Thus interpreted, conduct is the resultant of numerous forces arising from the interaction of internal and external factors; it is a changeable current based on the ratio of forces inherent in the biologic constitution of man and the counter resistances of the social world in
Reply to K. Filanovsky et al
Authors: Patrice Chevallier, Jacques Delaunay, Pascal Turlure, Arnaud Pigneux, Mathilde Hunault, Richard Garand, Thierry Guillaume, Herve Avet-Loiseau, Nathalia Dmytruk, Stephane Girault, Noel Milpied, Norbert Ifrah, Mohamad Mohty, Jean-Luc Harousseau
Journal: Journal of Clinical Oncology (2010)
Virological response to interferon treatment in hepatitis C virus carriers with normal aminotransferase levels and chronic hepatitis
Authors: A Rossini, A Ravaggi, L Biasi, E Agostinelli, L Bercich, G B Gazzola, F Callea, E Radaeli, E Cariani
Journal: Hepatology (1997)

Hepatitis C virus (HCV) carriers with normal aminotransferase levels often show histological chronic hepatitis. This study was undertaken to determine the effect of interferon (IFN) in such patients. Nineteen HCV carriers with normal aminotransferase activities and chronic hepatitis were randomized to receive IFN-alpha2b (3 million units 3 times weekly for 12 months) or no treatment. Therapy was monitored by qualitative and quantitative determination of viral RNA. Patients who did not clear HCV RNA after 6 months discontinued therapy. In all, 9 patients constituted the control group, while 10 patients were treated. Five of these patients, still viremic after 6 months, stopped IFN. The remaining 5 patients, who cleared the viral RNA within 6 months, completed the 12-month course. Three of these patients relapsed off treatment, and 2 were still free of viremia 12 months after stopping therapy. A transient flare-up of aminotransferase activities was detected in 2 patients during treatment and in 3 patients after. None of the 9 control patients cleared the viral RNA during follow-up. A variable degree of sequence heterogeneity was detected in the hypervariable region before therapy, and IFN treatment decreased sequence diversity in all patients. These results indicate that IFN therapy can be effective in chronic HCV carriers with normal aminotransferase activities, inducing short-term virological response in 3 of 10 patients and sustained response in 2. The effects of treatment on viral load and quasispecies complexity were similar to those reported previously in patients with increased aminotransferase activities.
Contribution of Glycogen to Aerobic Myocardial Glucose Utilization
Authors: Sarah L. Henning, Richard B. Wambolt, Brett O. Schönekess, Gary D. Lopaschuk, Michael F. Allard
Journal: Circulation (1996)

We determined glycogen turnover and the contribution of glycogen as a source of glucose for aerobic myocardial glycolysis and glucose oxidation in parallel series of isolated, working rat hearts subjected to pulse-chase perfusions.Myocardial glycogen of isolated, working rat hearts was radiolabeled, after 30 minutes of substrate-free glycogen depletion, by perfusion for 60 minutes with buffer designed to stimulate resynthesis of glycogen (1.2 mmol/L palmitate, 11 mmol/L [U-14C]- or [5-3H]glucose, 0.5 mmol/L lactate, and 100 microU/mL insulin). Rates of glucose oxidation (14 CO2 production) and glycolysis (3H20 production) were then measured by perfusing the hearts for 40 minutes with buffer designed to simulate physiological conditions (0.4 mmol/L palmitate, 0.5 mmol/L lactate, 11 mmol/L [5-3H]- or [U-14C]- glucose, 100 microU/mL insulin) containing radiolabeled glucose different from that used during resynthesis. During the chase perfusion, rates of glycolysis and glucose oxidation from exogenous glucose were significantly greater than those from endogenous glycogen. Nevertheless, glycogen contributed significantly to myocardial energy production (41% of the overall ATP produced from glucose), and a significantly greater fraction of the glucose from glycogen that passed through glycolysis was oxidized (>50%) compared with the fraction oxidized from exogenous glucose (<20%, P<.05). Myocardial glycogen was simultaneously synthesized and degraded (ie, glycogen turnover) during the chase perfusion, despite net glycogenolysis. Furthermore, enrichment of labeled glucose in glycogen at the end of the chase perfusion, when corrected for newly synthesized glycogen, did not differ from that at the end of the labeling period.Thus, glycogen contributes significantly to aerobic myocardial glucose use under these experimental conditions, and the glucose derived from glycogen is oxidized preferentially compared with exogenous glucose. Additionally, substantial myocardial glycogen turnover occurs, and the manner in which glycogen is degraded does not fit the ordered hypothesis of "last glucose on, first glucose off."
Derivation and Validation of Multimarker Prognostication for Normotensive Patients with Acute Symptomatic Pulmonary Embolism
Authors: David Jiménez, Dita Kopecna, Victor Tapson, Beau Briese, Donald Schreiber, José Luis Lobo, Manuel Monreal, Drahomir Aujesky, Olivier Sanchez, Guy Meyer, Stavros Konstantinides, Roger D. Yusen, None on behalf of the PROTECT Investigators
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Not all patients with acute pulmonary embolism (PE) have a high risk of an adverse short-term outcome.Objectives: This prospective cohort study aimed to develop a multimarker prognostic model that accurately classifies normotensive patients with PE into low and high categories of risk of adverse medical outcomes.Methods: The study enrolled 848 outpatients from the PROTECT (PROgnosTic valuE of Computed Tomography) study (derivation cohort) and 529 patients from the Prognostic Factors for Pulmonary Embolism (PREP) study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, hemodynamic collapse, and/or adjudicated recurrent PE.Measurements and Main Results: A complicated course occurred in 63 (7.4%) of the 848 normotensive patients with acute symptomatic PE in the derivation cohort and in 24 patients (4.5%) in the validation cohort. The final model included the simplified Pulmonary Embolism Severity Index, cardiac troponin I, brain natriuretic peptide, and lower limb ultrasound testing. The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the simplified Pulmonary Embolism Severity Index and brain natriuretic peptide testing showed a negative predictive value for a complicated course of 99.1 and 100% in the derivation and validation cohorts, respectively. The combination of all modalities had a positive predictive value for the prediction of a complicated course of 25.8% in the derivation cohort and 21.2% in the validation cohort.Conclusions: For normotensive patients who have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, hemodynamic collapse, and/or recurrent PE within the following 30 days.
Distinct Roles of the Phosphatidylinositol 3-Kinase and STAT5 Pathways in IL-7-Mediated Development of Human Thymocyte Precursors
Authors: Caroline Pallard, Alexander P.A Stegmann, Titia van Kleffens, Fiona Smart, Ashok Venkitaraman, Hergen Spits
Journal: Immunity (1999)
Meta-analysis suggests that intensive non-biological combination therapy with step-down prednisolone (COBRA strategy) may also ‘disconnect’ disease activity and damage in rheumatoid arthritis
Authors: Maarten Boers, Lilian van Tuyl, Marianne van den Broek, Piet J Kostense, Cornelia F Allaart
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background/objective</h3> Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF) antagonists changes the relationship between disease activity and progression of radiological joint damage ('disconnect'): patients who have little or no response of disease activity still show reductions in damage progression. In early RA, the COBRA strategy (combination of methotrexate and sulfasalazine with step-down prednisolone) has been shown to be equivalent to high-dose methotrexate and infliximab in suppressing damage progression (BeSt trial). We investigated whether COBRA treatment can also 'disconnect' disease activity and damage. <h3>Design</h3> A meta-analysis combined data from the COBRA trial (COBRA vs sulfasalazine monotherapy) with that of two arms of the BeSt trial (COBRA vs sequential monotherapy). Linear regression related 1-year progression of damage (Sharp van der Heijde score) as a dependent variable with disease activity (time-averaged Disease Activity Score in 44 joints (DAS44) or C-reactive protein (CRP)), treatment strategy (COBRA or control) and their interaction (indicator of a disconnect) as independent variables. The main outcome was the pooled interaction term. <h3>Results</h3> Complete data from 60–100% of patients were available. Before pooling, disease activity was the only (strongly) significant independent factor related to damage progression. The pooled interaction term was (weakly) significant: time-averaged DAS44×treatment interaction, one-sided p=0.027; time-averaged CRP×treatment interaction, one-sided p=0.044. <h3>Conclusions</h3> Changes in the relationship between disease activity and damage progression may not be limited to anti-TNF treatment, but a property of early, rapid and deep suppression of joint inflammation, also induced by conventional strategies that include glucocorticoids.
The debate over mass mammography in Britain. The case against.
Authors: P. Skrabanek
Journal: BMJ (1988)

On the day that the Forrest report was published Norman Fowler announced that the government was going to implement its recommendations.Those who were invited to give evidence to the working party were bound to secrecy about the matters discussed, and as a result dissent was, at least in the short term, effectively silenced.The Forrest report is a consensus document that does not mention the arguments of the dissenting minority.Its recommendations are based on selective evidence, which ignores data that might undermine its unrealistic estimates.
Rehashing endocannabinoid antagonists: can we selectively target the periphery to safely treat obesity and type 2 diabetes?
Authors: Mary-Elizabeth Patti
Journal: Journal of Clinical Investigation (2010)

A growing body of evidence supports an important role for the endocannabinoid system as a regulator of appetite, body weight, and systemic metabolism, which is overactive in obesity and type 2 diabetes. While initial attempts to target this system using the cannabinoid receptor inverse agonist rimonabant were successful in producing modest weight loss and improving obesity-related metabolic complications in humans, adverse central nervous system side effects precluded introduction of this drug into clinical practice. However, new data, presented by Tam and colleagues in this issue of the JCI, demonstrate that selective blockade of peripheral cannabinoid receptors may be a novel successful therapeutic approach.
Small-Pox and Scarlet Fever Disinfectants
Authors: C. Roberts
Journal: BMJ (1871)

Mr. C., wherein the daily use of the Turkish Bath has been equally as efficacious.This would weary you, and is, however, unnecessary, as my object is to bring before you the fact, obtained from some consi- derable experience, of the utility of the Turkish bath in diminishing dropsical accumulations-more especially those caused by Bright's dis- ease of the kidney-and with the hope of inducing some of you at least to try so valuable an agent.
Dying Patients in the Intensive Care Unit
Authors: Stephen Workman
Journal: Annals of Internal Medicine (2001)

Letters18 December 2001Dying Patients in the Intensive Care UnitStephen Workman, MD, MSc, FRCPStephen Workman, MD, MSc, FRCPDalhousie University; Halifax, Nova Scotia B3H 2S9, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-12-200112180-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In the article by Faber-Langendoen and Lanken on dying patients in the intensive care unit (ICU), part of the case report states, “The ICU physician tells Mrs. McGee that her husband's chance of surviving is less than 10% and that even if he does survive, he will need long-term ventilator support and dialysis. Although Mr. McGee has no written advance directive, his family is certain that he would not want ICU care continued given the prospects” (1).Although the article itself was very helpful, the conversational template was less so. How is it known that the chance ...Reference1. Faber-Langendoen K, Lanken PN. Dying patients in the intensive care unit: forgoing treatment, maintaining care. Ann Intern Med. 2000;133:886-93. [PMID: 11103059] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Dalhousie University; Halifax, Nova Scotia B3H 2S9, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDying Patients in the Intensive Care Unit: Forgoing Treatment, Maintaining Care Kathy Faber-Langendoen and Paul N. Lanken Dying Patients in the Intensive Care Unit Kathy Faber-Langendoen and Paul N. Lanken Metrics 18 December 2001Volume 135, Issue 12Page: 1091-1092KeywordsIntensive care unitsMedical dialysisVentilators ePublished: 18 December 2001 Issue Published: 18 December 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hsp90 Inhibition Overcomes HGF-Triggering Resistance to EGFR-TKIs in EGFR-Mutant Lung Cancer by Decreasing Client Protein Expression and Angiogenesis
Authors: Hitomi Koizumi, Tadaaki Yamada, Shinji Takeuchi, Takayuki Nakagawa, Kenji Kita, Takahiro Nakamura, Kunio Matsumoto, Kenichi Suda, Tetsuya Mitsudomi, Seiji Yano
Journal: Journal of Thoracic Oncology (2012)
Neuropsychopharmacology and the Affective Disorders
Authors: Joseph J. Schildkraut
Journal: New England Journal of Medicine (1969)

DRUGS that are clinically effective in the treatment of the affective disorders — depressions and manias — have also been found to be important tools for research in psychiatry during the past decade.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Since these disorders, particularly the depressions, represent a heterogeneous collection of entities, their differential diagnosis and classification have occasioned a long standing controversy.18 , 19 A discussion of the diagnosis and classifications of the affective disorders is necessary, however, if the action of the agents developed to treat them is to be understood.Diagnosis and Classifications of the Affective DisordersThe term "depression" as it is commonly used in . . .
Carcinoid Tumors of the Rectum
Authors: James K. McGregor
Journal: JAMA (1962)

CARCINOID TUMORS of the rectum are uncommon, slow-growing, malignant submucosal lesions having full potentialities for local invasion and widespread metastatic dissemination. They were first described by Lubarsch in 1888 and named by Oberndorfer in 1907. Since that time they have been reported occurring in almost any tissue derived from primitive ectoderm as well as in teratomas. They are, however, most frequently encountered in the appendix. Occurrence within the rectum was first recorded by Saltykow in 1912. With the acceptance of proctosigmoidoscopy as an established procedure in the routine physical examination, the occurrence of this lesion in the rectum has been mentioned with increasing frequency.  These tumors are derived from the Kulschitzky (or argentaffin) cells located deep in the crypts of Lieberkuhn. Initially these lesions, like simple adenomata, have no characteristic signs or symptoms. But upon examination, they are found to be small, rubbery, firm, discrete, freely movable, nonencapsulated, nodular thickenings
Abstract 5176: Implications of clonality relationship and CD133 expression between cancer synchronous/preceding adenomas and their colorectal adenocarcinoma pairs
Authors: Chih-Yung Yang, Ju-Yu Tseng, Chi-Hung Lin
Journal: Cancer Research (2014)

Abstract Background: It is thought that each cell only generates a unifocal lineage that is independent from one another in colorectal adenoma-carcinoma progression. This study compared the genome-wide copy number aberration profiles of adenoma and primary colorectal carcinomas (CRCs) derived from the same patient to trace their clonality relationship. The CD133 positive cells, putative colorectal cancer stem cells, are capable of tumor initiation and metastasis. Therefore, we also investigated the use of CD133 expression as a potential marker for prediction of subsequent risk of colorectal cancer. Methods: Microarray-based comparative genomic hybridization (aCGH) experiments were performed on 18 cancer-synchronous polyps (CSP) and 9 cancer-preceding polyps (CPP), together with their corresponding cancers, and 16 cases of incidental polyps (IP). Genome-wide copy number imbalances revealed by aCGH were analyzed to determine the clonal relationship between the paired adenomas and carcinomas. CD133 expression in cancerous tissue was evaluated by immunohistochemistry (IHC) staining. Results: There were more CGH lesions in CRC than CSP/CPP, and least in IP. Clonal relationship determined by tissues' aCGH profiles showed that 50 percent of CSP and 67 percent of CPP were clonally related to the concurrent or subsequent cancers, respectively. The expression level of stem cell marker CD133 was significantly higher in CSP/CPP than in IP (P&amp;lt;0.0001), and even higher CD133 staining were observed in CSP/CPP that were clonally related to the corresponding carcinomas than CSP/CPP that were unrelated (P&amp;lt;0.05). Conclusions: In the present study more than half of the polyp-carcinoma pairs share highly similar pattern of numerical chromosomal aberrations implying that the pairs might descent from the same monoclonal cell origin. The high expression of stem cell marker CD133 in colorectal adenomas is predictive of high cancer risk for polyp-bearing patients. Citation Format: Chih-Yung Yang, Ju-Yu Tseng, Chi-Hung Lin. Implications of clonality relationship and CD133 expression between cancer synchronous/preceding adenomas and their colorectal adenocarcinoma pairs. [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 5176. doi:10.1158/1538-7445.AM2014-5176
NI-41 * PROGNOSTIC SIGNIFICANCE OF DYNAMIC ANALYSIS OF 18FET-PET IN NEWLY DIAGNOSED HIGH GRADE GLIOMA
Authors: N. L. Jansen, B. Suchorska, V. Wenter, C. Schmid-Tannwald, M. Niyazi, P. Bartenstein, F.-W. Kreth, C. L. Fougere, J.-C. Tonn
Journal: Neuro-Oncology (2014)

PURPOSE: Despite advances in diagnosis and use of different therapeutic regimen in high grade gliomas (HGG), the prognosis for patients remains grim. Additional pre-therapeutic information is needed to tailor the management. In order to gain additional prognostic information at primary diagnosis we investigated the value of dynamic [18F]fluoroethyltyrosine (FET)-PET in patients with newly diagnosed HGG. METHODS: 131 patients with histologically verified HGG (61 WHO III°; 70 WHO IV°) and dynamic FET-PET prior to histopathological assessment were retrospectively evaluated. FET-PET analysis comprised the assessment of maximal tumor uptake (SUVmax/BG) and biological tumor volume (BTV), as well as kinetic evaluation including time-to-peak (TTP). The prognostic influence of PET parameters and clinical parameters on progression free and overall survival (PFS and OS) was evaluated using uni- and multivariate Cox-regression and Kaplan-Meier survival estimates. RESULTS: Median PFS and OS were 19.2 and 46.2 months in gliomas WHO III° and 10.3/14.2 months in IV° respectively. SUVmax/BG and BTV were significantly higher in WHO IV° compared to WHO III° gliomas. Median TTP was 12.5 minutes in both groups. The OS of WHO III° glioma patients with TTP > 12.5 minutes was significantly longer compared to TTP ≤ 12.5 minutes. In multivariate analysis, TTP was a significant prognostic factor for both OS and PFS besides WHO°, MGMT, and age. WHO and TTP reached a similar fit for the prognostic evaluation. CONCLUSIONS: Early TTP is associated with worse outcome in patients with newly diagnosed HGG. In the preoperative setting, TTP can be a valuable non-invasive prognostic marker with comparable significance to WHO grade. Additionally, TTP can help identify highly aggressive tumors among WHO III° glioma and might help adjusting standard treatment towards an individualised, risk-adapted therapy regime.