tbuckley/cabot-search huggingface dataset:
SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression
Authors: Justine M Kent
Journal: The Lancet (2000)

A major goal of antidepressant development is to improve on preceding drug classes with agents with greater specificity (and therefore fewer unwanted side-effects) and with more rapid onset of antidepressant action. To this end, four antidepressants with significantly distinct pharmacological characteristics have been recently introduced: venlafaxine, nefazodone, mirtazapine, and reboxetine. Venlafaxine is the first antidepressant in a new drug class referred to as the serotonin noradrenergic reuptake inhibitors (SNaRIs). Nefazodone is a weaker serotonin and norepinephrine reuptake inhibitor, but a potent serotonin 5-HT2 receptor antagonist. Mirtazapine is a potent antagonist of central 2α-adrenergic autoreceptors, and heteroreceptors and is an antagonist of serotonin 5-HT2 and 5-HT3 receptors. The result of these actions is to increase both noradrenergic and specific (5-HT1) serotonergic transmission, and mirtazapine has therefore been termed a noradrenergic and specific serotonergic antidepressant (NaSSA). Reboxetine is the first selective noradrenaline reuptake inhibitor (NaRI) to be introduced since the tricyclics, and lacks immediate serotonergic effects. A major goal of antidepressant development is to improve on preceding drug classes with agents with greater specificity (and therefore fewer unwanted side-effects) and with more rapid onset of antidepressant action. To this end, four antidepressants with significantly distinct pharmacological characteristics have been recently introduced: venlafaxine, nefazodone, mirtazapine, and reboxetine. Venlafaxine is the first antidepressant in a new drug class referred to as the serotonin noradrenergic reuptake inhibitors (SNaRIs). Nefazodone is a weaker serotonin and norepinephrine reuptake inhibitor, but a potent serotonin 5-HT2 receptor antagonist. Mirtazapine is a potent antagonist of central 2α-adrenergic autoreceptors, and heteroreceptors and is an antagonist of serotonin 5-HT2 and 5-HT3 receptors. The result of these actions is to increase both noradrenergic and specific (5-HT1) serotonergic transmission, and mirtazapine has therefore been termed a noradrenergic and specific serotonergic antidepressant (NaSSA). Reboxetine is the first selective noradrenaline reuptake inhibitor (NaRI) to be introduced since the tricyclics, and lacks immediate serotonergic effects. DEPARTMENT OF ERRORSNaRls, NaSSAs, and NaRls: new agents for the treatment of depression—In this Review by J Kent (March 11, p 911), the dose range for reboxetine in panel 3 on page 913 should have been 8–10 mg per day. Full-Text PDF
Abstract 1675: Lung cancer chemotherapy: genetic variations in the transforming growth factor beta pathway as predictors of survival
Authors: Moubin Lin, Michelle Hildebrandt, David Stewart, Scott M. Lippman, Charles Lu, Margaret R. Spitz, Xifeng Wu
Journal: Cancer Research (2010)

Abstract Treatments based on molecular determinants are likely to maximize therapeutic index for chemotherapy in non-small-cell lung cancer (NSCLC). The purpose of this study is to take a pathway-based approach to systematically evaluate the pharmacogenetic effects of transforming growth factor (TGF-β) pathway on lung cancer and identify potential genetic predictors of platinum-based chemotherapy. We genotyped 227 SNPS in 23 TGF-β pathways genes to evaluate their associations with overall survival in 598 late stage NSCLC patients receiving first-line platinum-based chemotherapy with or without radiotherapy. In individual analysis, 22 SNPs were significantly associated with overall survival, of which the strongest associations were found for BMP2:rs235756 (HR=1.45; 95%CI, 1.11-1.90; P=0.006) and SMAD3:rs4776342 (HR=1.25; 95%CI, 1.06-1.47; P=0.009). Cumulative effect analysis showed that individuals with multiple risk genotypes had a significant dose-dependent adverse affect on overall survival (Ptrend=2.44×10−15). Analysis stratified by treatment modality showed that SMAD3 haplotypes exhibited significant associations with outcomes of chemotherapy. Survival tree analysis categorized subgroups of patients with dramatically different survival pattern. The low-risk genetic profile group identified from patients treated with chemoradiation had a median survival time (MST) of 30.4 months. In comparison, the high-risk genetic profile group had a more than four-fold increased risk of death with MST of 6.8 months. The low-risk genetic profile group identified from patients treated with primary chemotherapy without definitive radiotherapy had a MST of 18.03 months, while the high-risk genetic profile group had a MST of 5.9 months and a four-fold increased risk of death. These results suggest that genetic variations in TGF-β pathway are potential predictors for clinical outcome in advanced NSCLC treated with platinum-based chemotherapy. We also found that genetic variations within the TGF-β signaling pathway may be able to identify potential subgroups of patients who will most benefit from platinum-based chemotherapy with or without radiotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1675.
Curcumin Inhibits Lung Cancer Cell Invasion and Metastasis through the Tumor Suppressor HLJ1
Authors: Huei-Wen Chen, Jen-Yi Lee, Ji-Ying Huang, Chi-Chung Wang, Wan-Jiun Chen, Sheng-Fang Su, Chia-Wen Huang, Chao-Chi Ho, Jeremy J.W. Chen, Meng-Feng Tsai, Sung-Liang Yu, Pan-Chyr Yang
Journal: Cancer Research (2008)

Abstract Curcumin (diferuloylmethane) is an active component of the spice turmeric and has a diversity of antitumor activities. In this study, we found that curcumin can inhibit cancer cell invasion and metastasis through activation of the tumor suppressor DnaJ-like heat shock protein 40 (HLJ1). Human lung adenocarcinoma cells (CL1-5) treated with curcumin (1–20 μmol/L) showed a concentration-dependent reduction in cell migration, invasion, and metastatic ability, and this was associated with increased HLJ1 expression. Knockdown of HLJ1 expression by siRNA was able to reverse the curcumin-induced anti-invasive and antimetastasis effects in vitro and in vivo. The HLJ1 promoter and enhancer in a luciferase reporter assay revealed that curcumin transcriptionally up-regulates HLJ1 expression through an activator protein (AP-1) site within the HLJ1 enhancer. JunD, one of the AP-1 components, was significantly up-regulated by curcumin (1–20 μmol/L) in a concentration- and time-dependent manner. Knockdown of JunD expression could partially reduce the curcumin-induced HLJ1 activation and diminish the anti-invasive effect of curcumin, indicating that JunD would seem to be involved in curcumin-induced HLJ1 expression. Curcumin was able to induce c-Jun NH2-kinase (JNK) phosphorylation, whereas the JNK inhibitor (SP-600125) could attenuate curcumin-induced JunD and HLJ1 expression. Activation of HLJ1 by curcumin further leads to up-regulation of E-cadherin and a suppression of cancer cell invasion. Our results show that curcumin induces HLJ1, through activation of the JNK/JunD pathway, and inhibits lung cancer cell invasion and metastasis by modulating E-cadherin expression. This is a novel mechanism and supports the application of curcumin in anti–cancer metastasis therapy. [Cancer Res 2008;68(18):7428–38]
Abstract 553: Host cell OGR1 plays an important role in TRAMP cell tumorigenesis
Authors: Libo Yan, Gang Wei, Hui Li, Zhenwen Zhao, Lisam Shanjukumar Singh, Yan Xu
Journal: Cancer Research (2010)

Abstract Ovarian cancer G protein coupled receptor 1 (OGR1) was previously cloned from an ovarian cancer cell line HEY. We have recently shown that OGR1 is a new tumor metastasis suppressor gene in prostate cancer. To further understand the physiological role of OGR1, we have generated OGR1 knockout (KO) mice. These mice are viable and grossly normal under regular physiological conditions. To exam the role of host cell OGR1 in prostate cancer development, TRAMP-C2 cells (a mouse prostate cancer cell line) were subcutaneously (s.c.) injected into OGR1 KO mice, significantly reduced tumorigenesis were observed when compared to that in wild type (WT) mice. 100% (20 of 20) of wild type mice developed tumors, while only 12.5% (4 of 32) of OGR1 deficient mice developed small tumors. To test whether OGR1 deficiency in host cells inhibits tumorigenesis of other mouse prostate tumor cells, RM-9 cells (an aggressive and poorly immunogenic mouse prostate tumor cells) were subcutaneously injected into OGR1 KO and WT mice (2 mice/group). All 4 mice developed big tumors at 10 days post tumor cell injection. No significant difference was observed between WT and OGR1 KO mice. Thus, host OGR1 deficiency differentially affected tumorigenesis of TRAMP and RM-9 cells, suggesting a tumor cell type specific effect. OGR1 are highly expressed in immune cells. We are currently testing whether these cells are functionally involved in host OGR1's effects. In addition, fibroblasts have a prominent role in the progression, growth and spread of cancers. The infiltration of fibroblasts in TRAMP-C2 tumors from WT and OGR1 KO mice were tested. Decreased fibroblast infiltration was observed in tumors from the KO vs. WT mice. The expression of OGR1 in mouse fibroblasts were confirmed by RT-PCR. Our results suggest that fibroblasts may be involved in OGR1's effect on tumorigenesis. Our new findings may lead to novel therapeutic strategies for prostate and/or other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 553.
EXPERIMENTS ON THE TRANSMISSION OF SCARLET FEVER TO THE LOWER MONKEYS
Authors: George Draper, John M. Hanford
Journal: The Journal of Experimental Medicine (1913)

1. The reported successful transfer of scarlet fever to both higher and lower monkeys is not definitely established. 2. In the course of the experiments here reported, the infectious agent can be assumed to have been carried over to the monkeys. The failure to cause infection probably proceeds from the insusceptibility of the monkeys employed, or to the manner of introducing the agent. 3. The temperature curve and leucocyte count of monkeys are unsatisfactory criteria for the diagnosis of disease in those animals. 4. Monkeys frequently have transient blotchy, erythematous eruptions on the face and neck, and almost always a bran-like desquamation. 5. Monkeys are highly resistant to infection with microorganisms from human beings.
OILY INJECTIONS OF SALVARSAN—A WARNING
Authors: H. H. HAZEN
Journal: JAMA (1913)

three hundred children of the institution, but as an illustration give a table showing the reactions of some children (those whose names begin with the letters A and B) in order to show the constancy of the tests from year to year (Table 2).It will he seen that negative reactions do not become positive in the insti¬ tution.There has been no instance in which we have met two negative reactions followed by a positive reac¬ tion, such as we sec throughout the tahle showing the ward infection (Table 1).We must conclude, therefore, Ihal these children were all infected by this attendant during a period of exposure of six weeks.It should be mentioned, however, that a
Vitamin D Receptor Attenuates Renal Fibrosis by Suppressing the Renin-Angiotensin System
Authors: Yan Zhang, Juan Kong, Dilip K. Deb, Anthony Chang, Yan Chun Li
Journal: Journal of the American Society of Nephrology (2010)

Analogs of vitamin D attenuate renal injury in several models of kidney disease, but the mechanism underlying this renoprotective effect is unknown. To address the role of the vitamin D receptor (VDR) in renal fibrogenesis, we subjected VDR-null mice to unilateral ureteral obstruction for 7 days. Compared with wild-type mice, VDR-null mice developed more severe renal damage in the obstructed kidney, with marked tubular atrophy and interstitial fibrosis. Significant induction of extracellular matrix proteins (fibronectin and collagen I), profibrogenic and proinflammatory factors (TGF-beta, connective tissue growth factor, and monocyte chemoattractant protein 1), and epithelial-to-mesenchymal transition accompanied this histologic damage. Because VDR ablation activates the renin-angiotensin system and leads to accumulation of angiotensin II (AngII) in the kidney, we assessed whether elevated AngII in the VDR-null kidney promotes injury. Treatment with the angiotensin type 1 antagonist losartan eliminated the difference in obstruction-induced interstitial fibrosis between wild-type and VDR-null mice, suggesting that AngII contributes to the enhanced renal fibrosis observed in obstructed VDR-null kidneys. Taken together, these results suggest that the VDR attenuates obstructive renal injury at least in part by suppressing the renin-angiotensin system.
510 PREVENTION OF LIVER ISCHEMIA/REPERFUSION INJURY BY MODULATING INTESTINAL FLORA: AN ATTRACTIVE APPROACH
Authors: A. Cannesson, S. Dharancy, E. Gantier, D. Berrebi, A. Louvet, C. Neut, P. Mathurin, L. Dubuquoy
Journal: Journal of Hepatology (2011)
MY EXPERIENCE WITH SOLANUM CAROLINENSE IN THE TREATMENT OF EPILEPSY.
Authors: C. F. BARBER
Journal: JAMA (1895)

In February 1893, my attention was called to the use of<i>solanum carolinense</i>in epilepsy; accordingly, I made an effort to learn something of its efficacy, also of its source before utilizing it in my practice. I found<i>solanum carolinense</i>, or, as it is more commonly called, horse nettle, bull nettle or sand brier, was not official. It is not recognized by the U. S. Pharmacopœia, but a description, short, it is true, is found in the Dispensatory of 1894. It is a native of Florida and Carolina but is found as far north as Connecticut; grows from one to two feet in height, branching, and is covered with shaggy hairs which are armed with stout, straight, yellowish prickles. The leaves have the same armor for defense as do the stem and branches. The berries which are the fruit of the shrub are utilized in preparing the preparations used in
Improved transfection of spleen-derived antigen-presenting cells in culture using TATp-liposomes
Authors: Juan Sebastián Pappalardo, Valeria Quattrocchi, Cecilia Langellotti, Sebastián Di Giacomo, Victoria Gnazzo, Valeria Olivera, Gabriela Calamante, Patricia I. Zamorano, Tatyana S. Levchenko, Vladimir P. Torchilin
Journal: Journal of Controlled Release (2008)
To expunge politically sensitive topics from medical journals is “folly”
Authors: David Spurgeon
Journal: BMJ (2006)

John Hoey, until recently editor in chief of CMAJ , the journal of the Canadian Medical Association, last week broke his silence and spoke out about his firing and the firing of his deputy from their posts ( New England Journal of Medicine 2006;354:1982-3).

The association has never admitted to firing the two editors, but Dr Hoey writes that, on 20 February, after almost 10 years as editor in chief, “I was fired without cause,” along with Anne Marie Todkill, senior deputy editor and 12 year veteran. Until now, both he and Dr Todkill have declined to comment on their dismissals because of a confidentiality agreement with the CMA.

Dr Hoey said that the CMA gave no reasons “for the firings other than, initially, to ‘freshen’ the CMAJ and, later, for ‘irreconcilable differences’ (so far unspecified) between me and the CMA.” The most striking of these differences was …
E-cigarettes are to be regulated as medicines from 2016
Authors: I. Torjesen
Journal: BMJ (2013)

Electronic cigarettes and other electronic products containing nicotine are to be regulated as medicines in the United Kingdom from 2016, to ensure their quality and safety. Their use has grown dramatically in the UK since bans on smoking in enclosed public places came into being.

The move comes after an investigation into the products by the Medicines and Healthcare Products Regulatory Agency (MHRA). This investigation included a public consultation; a review of existing studies and the MHRA’s own commissioned research into the quality, safety, marketing, and use of the products; and an impact analysis on the consequences of regulation.1

The investigation confirmed that there were concerns about the safety and quality of e-cigarettes: levels of nicotine varied from what was listed on the label and from batch to batch, meaning that users don’t receive a consistent delivery of nicotine to deal with cravings; and they were often poorly manufactured, containing contaminants and with leaks of nicotine from …
Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project
Authors: Dennis D. Weisenburger, Kerry J. Savage, Nancy Lee Harris, Randy D. Gascoyne, Elaine S. Jaffe, Kenneth A. MacLennan, Thomas Rüdiger, Stefano Pileri, Shigeo Nakamura, Bharat Nathwani, Elias Campo, Francoise Berger, Bertrand Coiffier, Won-Seog Kim, Harald Holte, Massimo Federico, Wing Y. Au, Kensei Tobinai, James O. Armitage, Julie M. Vose
Journal: Blood (2011)
Complement induces a transient increase in membrane permeability in unlysed erythrocytes.
Authors: J A Halperin, A Nicholson-Weller, C Brugnara, D C Tosteson
Journal: Journal of Clinical Investigation (1988)

The effects of low concentrations of human serum on antibody-sensitized sheep erythrocytes (EA) were studied. We report that exposure to low concentrations of serum induced a large but transient increase in the membrane permeability of those EA that do not lyse. This change in the permeability of the erythrocyte membrane resulted in net uptake of Na+ and decrease in cell K+, without affecting the total internal cation content. Although exposure to serum also allowed for net uptake of larger molecules like L-glucose, it did not lead to cell swelling. Experiments with sera genetically deficient in one of the terminal complement components showed that C8, but not C9, was required to produce the observed change in membrane permeability. Therefore, we propose that the C5b-8 complex can mediate the transient increase in permeability observed in unlysed erythrocytes during complement activation by whole serum.
Bitten by a mouse
Authors: H V Wyatt
Journal: BMJ (2007)

Immunology is not an easy subject—it is complicated, and students soon lose interest. Lecturers can see the enthusiasm fading away and seek to enliven their lectures. I was intrigued by a well known US bacteriologist of the 1930s who had apparently solved the difficulty of keeping his students' attention when talking about complement—a complicated topic of little interest to them. He would enter …
TEMPORAL TRENDS IN REVASCULARIZATION AND OUTCOMES OF ST-ELEVATION MYOCARDIAL INFARCTION IN YOUNGER ADULTS IN THE UNITED STATES
Authors: Sahil Khera, Dhaval Kolte, Kathir Subramanian, Neel Khanna, Marjan Mujib, Wilbert Aronow, Chul Ahn, Chandrasekar Palaniswamy, Robert Timmermans, Howard Cooper, Gregg Fonarow, William Frishman, Julio Panza, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2015)
Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and neutrophils.
Authors: N Borregaard, K Kragballe
Journal: Journal of Clinical Investigation (1980)

The antibody-dependent cell-mediated cytoxicity (ADCC) by human monocytes and neutrophils was investigated by measuring the release of 51chromate from prelabeled erythrocytes coated with immunoglobulin G. ADCC was found to be positively correlated to phagocytosis of 51Cr-labeled erythrocytes and to the postphagocytic events of the effector cells, activation of the hexose monophosphate shunt, and degranulation. Exclusion of oxygen from the incubation media halved the ADCC by both cell types without affectijg phagocytosis or degranulation. Likewise, ADCC by cells from patients suffering from chronic granulomatous disease (CGD) was only half the intensity of ADCC by cells from normals. Inhibitors of mitochondrial respiration were without depressing effect of ADCC. Azide, which in addition to its blocking action on oxydative phosphorylation also inhibits catalase and myeloperoxidase, resulted in a approximately equal to 40% stimulation of ADCC by cells from normals but was without effect of ADCC by cells from CGD patients. The hydroxyl radical scavenger, mannitol, significantly depressed ADCC by cells from normals (P < 0.01) but was without effect on cells from CGD patients. Azide and mannitol also were without effect on ADCC by normal cells when oxygen was excluded. In a xanthine-xanthine oxidase system, erythrocytes were effectively lysed. This lysis was inhibited by catalase, superoxide dismutase, and mannitol. When comparable concentrations of glucose oxidase were used no lysis was observed. H2O2 either alone or in combination with azide did not lyse erythrocytes. It is suggested that ADCC by both monocytes and neutrophils is partly dependent on the generation of hydroxyl radicals by the effector cells.
DNA-protein cross-links as a biomarker of Cr(VI) exposure.
Authors: D J Paustenbach, B L Finley
Journal: Environmental Health Perspectives (1999)

Comment on A. Zhitkovich et al. :Utilization of DNA-protein cross-links as a biomarker of chromium exposure. Environ Health Perspect 106(suppl 4):969-974 (1998).
ULTRASONIC TEXTURAL CHANGES OF CAROTID INTIMA-MEDIA COMPLEX IN PATIENTS AFTER KAWASAKI DISEASE: COMPARISON WITH FINDINGS IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA AND CONTROL SUBJECTS AND VALIDATION IN A RAT MODEL
Authors: Nobutaka Noto, Michio Miyashita, Hiroshi Kanamaru, Kensuke Karasawa, Mamoru Ayusawa, Naokata Sumitomo, Tomoo Okada
Journal: Journal of the American College of Cardiology (2011)
Cocaine Abuse: New Directions in Treatment and Research
Authors: Wanda A. Taylor
Journal: JAMA (1989)

By now, everyone knows that cocaine use and addiction have become epidemic and treatment is multifactorial and very difficult. The cocaine epidemic began in the early-to-mid 1970s, but the books about it have been written in the late 1980s. In this book, edited by Spitz and Rosecan, studies and theories are presented by ten  University authors to enhance the readers' understanding of this complex addiction. This Columbia book is divided into four sections, the first of which is a historical overview of cocaine use through the ages. It contains interesting details ranging from the ritual use by the Incas in the 15th century to the self-experiments and wonder treatments proposed by Sigmund Freud.  The neurobiochemical aspects as well as the cognitive and behavioral aspects are addressed in the second section. It is here that clinical research studies are offered to support what these treating physicians have experienced clinically. The
Current state of total joint replacement.
Authors: M A Freeman
Journal: BMJ (1976)

In 1974 we sent questionnaires on attachment and employment of nurses to 9214 general practices in England.There were 7863 replies (850 ), of which 551 were excluded from the study.A total of 2654 nurses were directly employed by 240o (1774) of the practices, and 68% (4972) had attached nurses.Practices in health centres were larger and had greater nursing resources than those in other premises.We suggest that practices may employ nurses to compensate for ineffective nursing attachments, and we conclude that general-practiceemployed nurses are becoming "professionalised."
Validation of a New Risk Assessment Model for Predicting Adverse Events in Children With Fever and Chemotherapy-Induced Neutropenia
Authors: Karin G.E. Miedema, Eveline S.J.M. de Bont, Claudi S.M. Oude Nijhuis, Danique van Vliet, Willem A. Kamps, Wim J.E. Tissing
Journal: Journal of Clinical Oncology (2011)