tbuckley/cabot-search huggingface dataset:
A Possible Cardiovascular Effect of Lithium
Authors: Robert H. Belmaker, Rachel Lehrer, Richard P. Ebstein, Haya Lettik, Sol Kugelmass
Journal: American Journal of Psychiatry (1979)

Heart rate rises associated with performance of mental arithmetic tasks were compared in 22 euthymic manic-depressive patients receiving lithium carbonate and 17 drug-free normal controls. The lithium-treated subjects showed a markedly lower heart rate response to the mental arithmetic stimulus. No effect was observed on basal heart rate. The results are consistent with lithium's reported inhibition of noradrenaline-induced rises in adenylate cyclase activity but lack of inhibition of basal adenylate cyclase activity. The biochemical and psychophysiological findings may parallel lithium's unique ability to calm excited behavior without sedating normal behavior.
A study of low-dose amitriptyline overdoses
Authors: J P O'Brien
Journal: American Journal of Psychiatry (1977)

Although a 1-week supply of tricyclic antidepressants is generally considered safe, the author shows that this amount can be severely toxic. Six of 12 instances of low-dose (500-1000 mg) amitriptyline overdoses were life threatening. The author suggests that prescription guidelines for tricyclic antidepressants be tightened and that physicians prescribe less than a 1-week supply to potentially suicidal patients.
UFMylation: A Unique &amp; Fashionable Modification for Life
Authors: Ying Wei, Xingzhi Xu
Journal: Genomics Proteomics & Bioinformatics (2016)

Ubiquitin-fold modifier 1 (UFM1) is one of the newly-identified ubiquitin-like proteins. Similar to ubiquitin, UFM1 is conjugated to its target proteins by a three-step enzymatic reaction. The UFM1-activating enzyme, ubiquitin-like modifier-activating enzyme 5 (UBA5), serves as the E1 to activate UFM1; UFM1-conjugating enzyme 1 (UFC1) acts as the E2 to transfer the activated UFM1 to the active site of the E2; and the UFM1-specific ligase 1 (UFL1) acts as the E3 to recognize its substrate, transfer, and ligate the UFM1 from E2 to the substrate. This process is called ufmylation. UFM1 chains can be cleaved from its target proteins by UFM1-specific proteases (UfSPs), suggesting that the ufmylation modification is reversible. UFM1 cascade is conserved among nearly all of the eukaryotic organisms, but not in yeast, and associated with several cellular activities including the endoplasmic reticulum stress response and hematopoiesis. Furthermore, the UFM1 cascade is closely related to a series of human diseases. In this review, we summarize the molecular details of this reversible modification process, the recent progress of its functional studies, as well as its implication in tumorigenesis and potential therapeutic targets for cancer.
Abstract A43: Long noncoding RNAs as targets of mammary tumor cell proliferation and migration
Authors: Sarah D. Diermeier, Kung-Chi Chang, Susan M. Freier, Frank Rigo, C. Frank Bennett, David L. Spector
Journal: Cancer Research (2016)

Abstract Objective: Recent genome-wide studies revealed that as much as 80% of the human genome can be transcribed whereas only 2% of this RNA is translated into proteins. Non-coding transcripts can be subdivided into several groups, with long non-coding RNAs (lncRNAs) representing the largest and most diverse class. With breast cancer being the most frequent malignancy in women worldwide, we set out to investigate the potential of lncRNAs as novel therapeutic targets. Methods: We focused on the luminal B and the HER2/neu-positive subtypes of breast cancer, as both are associated with high prevalence and bad prognosis. By performing RNA-Seq on tumor sections and mammary organoids from MMTV-PyMT and MMTV-Neu-NDL mice, modeling the luminal B and HER2/neu-amplified subtypes of human breast cancer respectively, we generated a comprehensive catalog of differentially expressed lncRNAs. We functionally validated the role of a subset of these lncRNAs by antisense oligonucleotide (ASO) mediated knockdown in primary mammary tumor cells and 3D ex vivo organoids. Results: We identified several hundred potentially oncogenic lncRNAs that were over-expressed in a subtype-specific manner as well as numerous lncRNAs up-regulated in both MMTV-PyMT and MMTV-Neu-NDL tumors. To narrow down the candidate list of lncRNAs with the highest therapeutic potential, we sorted the data computationally and defined a subset of previously uncharacterized lncRNAs as Mammary Tumor Associated RNAs (MaTARs). Upon independent knockdown of several MaTARs, we observed significantly reduced cell proliferation, invasion and/or collective cell migration in a cancer-specific context. Conclusion: MaTARs are likely important drivers of mammary tumor progression and/or metastasis and represent promising new therapeutic targets. Future studies will focus on the molecular characterization of these lncRNAs and elucidation of their potential role(s) in mammary tumor progression and metastasis. Citation Format: Sarah D. Diermeier, Kung-Chi Chang, Susan M. Freier, Frank Rigo, C. Frank Bennett, David L. Spector. Long noncoding RNAs as targets of mammary tumor cell proliferation and migration. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A43.
Abstract IA01: The origins of ovarian cancer.
Authors: Kathleen R. Cho
Journal: Clinical Cancer Research (2016)

Abstract Ovarian cancer is a generic term that can be used for any malignant ovarian tumor. The majority of ovarian cancers are carcinomas, i.e., malignancies with epithelial differentiation. Ovarian carcinomas represent a heterogeneous group of tumors that can be divided into five major types based largely on their light microscopic appearance. Notably, the origins of these different tumor types (high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma) remain incompletely understood. Indeed, many ovarian cancers may not actually originate in the ovaries, but instead involve the ovaries secondarily. Even those that develop in the ovaries may arise from cell types, for example endometrial- or fallopian tube-type epithelium, that are not considered intrinsic to normal ovaries. Potential origins and putative precursors of the five major types of ovarian carcinoma will be reviewed and experimental data from mouse models supporting a role for the ovarian surface epithelium and/or fallopian tube epithelium will be presented. A more complete understanding of the origin(s) of each type of ovarian carcinoma is needed to inform the development of effective ovarian cancer prevention, early detection and treatment strategies. Citation Format: Kathleen R. Cho. The origins of ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA01.
Ernest Gruening
Authors: James Howard Means
Journal: New England Journal of Medicine (1954)

A DOCTOR far afield from the medical point of view, but very far from afield in the career he finally elected to follow, is the Honorable Ernest Gruening, M.D., LL.D., journalist, public servant and statesman.Gruening was a member of the Harvard College Class of 1907 and of the Harvard Medical School Class of 1911. Actually, he left the Medical School in the middle of his fourth year to take a job as cub reporter for the Boston American. Then and there he switched careers from medicine to journalism, or as he put it himself, he "decided to give . . .
Results of a Phase II Study of Lenalidomide in Combination with Rituximab for the Treatment of Indolent Non Follicular Non Hodgkin Lymphoma (NHL)
Authors: Stefano Sacchi, Samantha Pozzi, Marina Cesaretti, Luigi Marcheselli, Eliana Valentina Liardo, Gabriele Buda, Antonio Lazzaro, Luca Baldini, Francesco Di Raimondo, Pellegrino Musto, Alfonso Zaccaria, Giorgina Specchia, Umberto Vitolo, Massimo Magagnoli, Franco Silvestris, Pier Paolo Fattori, Patrizia Tosi, Angelo Michele Carella
Journal: Blood (2012)
Developing the Community reporting system for foodborne outbreaks
Authors: A Gervelmeyer, M Hempen, U Nebel, C Weber, S Bronzwaer, A Ammon, P Makela
Journal: Eurosurveillance (2008)

Investigating and reporting of foodborne outbreaks became mandatory with Directive 2003/99/EC. In 2006 and 2007 the Community reporting system for foodborne outbreaks was further developed in an interdisciplinary approach, which is described in this paper. This involved experts on investigating and reporting foodborne outbreaks as well as experts on communicable diseases in addition to the European Food Safety Authority (EFSA) Task Force for Zoonoses Data Collection, the European Centre for Disease Prevention and Control (ECDC) Advisory Forum and representatives of ECDC, the World Health Organization (WHO), the World Organization for Animal Health (OIE) and the European Commission. European Union Member States participated in a survey regarding their national reporting systems and the needs for information on foodborne outbreaks at the Community level. The acceptability, the functionality and the data quality of the current reporting system were evaluated. The results were used to propose new variables on which data should be reported. Pick-lists were developed to facilitate reporting and better integration of the Community system with Member States' reporting systems. The new system is expected to yield better quality data on foodborne outbreaks relevant for risk assessment and risk management while reducing the work load for Member States.
Survival differences in colorectal cancer (CRC) on the basis of race: University of Pittsburgh Medical Center (UPMC) experience
Authors: R. Sehgal, W. McHayleh, B. C. Lembersky, J. J. Schlesselman, S. Evans, Y. Shuai, S. Winters, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2008)

4041 Background: CRC has higher 5-yr survival in whites (W) (65%) as compared to African Americans (AA) (55%). Our study was aimed to detect factors that might affect survival in these two groups at UPMC. Methods: Of 2,494 patients (pts) diagnosed with CRC at UPMC from 1994–2005, complete data (age, sex, disease status, tumor characteristics, treatment & overall survival) were available for 1,800 pts (181 AA & 1619 W). Results: Average age was 68 yrs in AA vs 69 in W. Pts with stage I, II, III, & IV in AA vs W were 22% vs 18%, 27% vs 34%, 32% vs 29% & 19% vs19%, respectively. Tumor grade differentiation in AA vs W was well (WD) in 2% vs 3%, moderate (MD) in 83% vs 76 %, poor (PD) in 14%vs 20% and undifferentiated (UD) in 1% vs 1% of pts, respectively. Median (M) time from diagnosis to starting treatment was 8 days in AA vs 11 in W. M number (no.) of lymph nodes (LN) examined were 12 in AA vs 14 in W. Overall M survival time (MST) was 49 months (m) in AA vs 67 m in W (p=0.09). MST for stage II+III pts was 49 vs 81 m (p<0.02) in AA and W respectively. On univariate analysis of stage II+III pts, factors affecting MST, in addition to race, were age (p<0.0001,HR 9.5 per 10-year increase), stage III vs II (p<0.003,HR 1.3), tumor grade PD,UD vs WD,MD (p=0.0004,HR 1.4),no. of involved LN (p<0.0001,HR1.1 per involved LN) & chemotherapy not received (p<0.0001,HR1.8). None of these factors individually or combined accounts for shorter MST in AA pts: multivariate adjusted HR 1.34 (AA vs W), p<0.04. Conclusions: AA pts with resected stage II/III CRC have significantly worse survival compared to W pts.This poorer survival cannot be explained by differences in age, disease stage, tumor grade, use of chemotherapy or inferior retrieval of LN. Co-morbidity or molecular factors, yet to be determined, must underlie the difference. No significant financial relationships to disclose.
Hospital use of antipsychotic agents in 1989 and 1993: stable dosing with decreased length of stay
Authors: R J Baldessarini, J C Kando, F Centorrino
Journal: American Journal of Psychiatry (1995)

This study evaluated recent and current use of antipsychotics by psychiatric inpatients.Computer-based hospital pharmacy records identified prescriptions for antipsychotics in 1993. Medical records were reviewed to verify prescription and clinical data, and these were compared with similar data from 1989.In 1993, antipsychotics were prescribed for 299 (42%) of 709 hospitalized patients. Treatment usually started within 24 hours of admissions averaging 18 days. High-potency agents were used 2.4 times more frequently than low-potency drugs; 13% received clozapine. The mean chlorpromazine-equivalent daily dose, corrected for as-needed supplements, was 305 mg; peak doses were 32% higher. Doses of the most potent agents (fluphenazine and haloperidol) were only 22%-33% above the overall mean. Rarely were two neuroleptics given simultaneously, but cotreatment with an anticonvulsant (84% of patients, 92% of whom received valproate), a potent benzodiazepine (81%), lithium (70%), one CNS depressant (84%), or more (45%) was common. Doses averaged 20% higher for men, 42% lower at age > 50 years versus 20-30 years, and 53% greater for schizophrenia or schizoaffective disorder versus other conditions. Comparison with 1989 admissions (N = 50) averaging 73 days indicated few differences in use of neuroleptics or benzodiazepines but less frequent use of anticonvulsants and lithium.High-potency antipsychotic agents and clozapine were used most often in 1993; doses of high-potency agents were only slightly higher than doses of low-potency agents, but combinations with mood stabilizers were more common in 1993, when length of stay was one-fourth that in 1989.
Immunisations among school leavers: is there a place for measles-mumps-rubella vaccine?
Authors: H P Lashkari, H El Bashir
Journal: Eurosurveillance (2010)

To ascertain measles-mumps-rubella (MMR) immunisation coverage among school leavers in an inner city London borough following a local MMR catch-up initiative, a questionnaire was sent to parents and guardians of adolescents who attended the 12 secondary schools in Haringey and were due for the school leavers' vaccination. The questionnaire enquired about previous history of MMR vaccination and a history of adverse events or contraindications to the vaccine. The electronic immunisation records of 400 children (30-35 students from each school) included in the catch up initiative were randomly selected. The childrens' school health records were manually compared with the electronic records. The mean age of the children was 14.7 years, and 224 (56%) were male. Of the 373 records examined prior to the local MMR catch-up initiative, 98 children (26%) had never received MMR, 173 (46.5%) had only had one dose, 100 (27%) had two doses, and two children had three doses of the vaccine. During the school leavers' MMR immunisation, 171 (43%) received a dose of MMR and the number of children immunised with two doses increased to 206 (55.3% versus 27% P<0.001), doubling the coverage. Offering MMR vaccination as part of the school leavers immunisation is logistically convenient and it may limit the extent of outbreaks.
Case 8-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Joseph L. Andrews, Eugene J. Mark
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 39-year-old woman was admitted to the hospital because of bilateral chest pain and pulmonary infiltrates.She was well until three months earlier, when pleuritic left precordial pain developed, accompanied by pain in the left humerus. A physician prescribed anxiolytic medication. She did not improve; the chest pain became more severe, and she returned to her physician. X-ray films of the chest (Fig. 1) showed nodular pulmonary densities, 3 to 7 mm, in both upper and mid-lung zones. The patient was told that she had pneumonia; an oral antibiotic medication was prescribed, again without improvement, and she . . .
Rho GTPase Transcriptome Analysis Reveals Oncogenic Roles for Rho GTPase-Activating Proteins in Basal-like Breast Cancers
Authors: Campbell D. Lawson, Cheng Fan, Natalia Mitin, Nicole M. Baker, Samuel D. George, David M. Graham, Charles M. Perou, Keith Burridge, Channing J. Der, Kent L. Rossman
Journal: Cancer Research (2016)

The basal-like breast cancer (BLBC) subtype accounts for a disproportionately high percentage of overall breast cancer mortality. The current therapeutic options for BLBC need improvement; hence, elucidating signaling pathways that drive BLBC growth may identify novel targets for the development of effective therapies. Rho GTPases have previously been implicated in promoting tumor cell proliferation and metastasis. These proteins are inactivated by Rho-selective GTPase-activating proteins (RhoGAP), which have generally been presumed to act as tumor suppressors. Surprisingly, RNA-Seq analysis of the Rho GTPase signaling transcriptome revealed high expression of several RhoGAP genes in BLBC tumors, raising the possibility that these genes may be oncogenic. To evaluate this, we examined the roles of two of these RhoGAPs, ArhGAP11A (also known as MP-GAP) and RacGAP1 (also known as MgcRacGAP), in promoting BLBC. Both proteins were highly expressed in human BLBC cell lines, and knockdown of either gene resulted in significant defects in the proliferation of these cells. Knockdown of ArhGAP11A caused CDKN1B/p27-mediated arrest in the G1 phase of the cell cycle, whereas depletion of RacGAP1 inhibited growth through the combined effects of cytokinesis failure, CDKN1A/p21-mediated RB1 inhibition, and the onset of senescence. Random migration was suppressed or enhanced by the knockdown of ArhGAP11A or RacGAP1, respectively. Cell spreading and levels of GTP-bound RhoA were increased upon depletion of either RhoGAP. We have established that, via the suppression of RhoA, ArhGAP11A and RacGAP1 are both critical drivers of BLBC growth, and propose that RhoGAPs can act as oncogenes in cancer. Cancer Res; 76(13); 3826-37. ©2016 AACR.
Pulsus Paradoxus
Authors: Maurice McGregor
Journal: New England Journal of Medicine (1979)

IT is well known that arterial pressure may fluctuate with the respiratory cycle, falling with inspiration and rising with expiration. This fluctuation occurs to a slight degree during normal breathing and may be more marked with forced respiratory effort, heart failure or pericardial tamponade.Ever since the phenomenon was first observed, suggested explanations have abounded. However, with the slow accumulation of knowledge on the relation between cardiac function and pleural pressure, it has now become possible to propose unifying concepts that account for the phenomenon both in normal and pathologic situations.Only two mechanisms seem to be involved. The first . . .
Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation
Authors: RJ D'Andrea, SC Barry, PA Moretti, K Jones, S Ellis, MA Vadas, GJ Goodall
Journal: Blood (1996)
Indocyanine Green-Loaded Polydopamine-Reduced Graphene Oxide Nanocomposites with Amplifying Photoacoustic and Photothermal Effects for Cancer Theranostics
Authors: Dehong Hu, Jingnan Zhang, Guanhui Gao, Zonghai Sheng, Haodong Cui, Lintao Cai
Journal: Theranostics (2016)

Photoacoustic (PA) imaging and photothermal therapy (PTT) as light-induced theranostic platforms have been attracted much attention in recent years. However, the development of highly efficient and integrated phototheranostic nanoagents for amplifying PA imaging and PTT treatments poses great challenges. Here, we report a novel phototheranostic nanoagent using indocyanine green-loaded polydopamine-reduced graphene oxide nanocomposites (ICG-PDA-rGO) with amplifying PA and PTT effects for cancer theranostics. The results demonstrate that the PDA layer coating on the surface of rGO could effectively absorb a large number of ICG molecules, quench ICG's fluorescence, and enhance the PDA-rGO's optical absorption at 780 nm. The obtained ICG-PDA-rGO exhibits stronger PTT effect and higher PA contrast than that of pure GO and PDA-rGO. After PA imaging-guided PTT treatments, the tumors in 4T1 breast subcutaneous and orthotopic mice models are suppressed completely and no treatment-induced toxicity being observed. It illustrates that the ICG-PDA-rGO nanocomposites constitute a new class of theranostic nanomedicine for amplifying PA imaging and PTT treatments.
Salt Poisoning
Authors: M. E. Calvin, R. Knepper, William O. Robertson
Journal: New England Journal of Medicine (1964)

THE recent Binghamton disaster, as summarized by Finberg et al.,¶ illustrated the toxic potential of "salt" in infancy. There, the inadvertent substitution of salt for sugar in the preparation of the newborn-nursery formula resulted in a "hyper-electrolyte formula" — and subsequently hypernatremic infants; 6 died. Other isolated reports of salt poisoning consequent to faulty formula preparation have been reported.We have recently seen a set of fourteen-month-old twins with salt poisoning who acquired their illness more directly. They simply ate salt!Case ReportAt 1:50 p.m. on April 19, 1963, 14-month-old twin Negro girls were admitted to the Columbus Children's . . .
Drug-induced liver injury caused by iodine-131
Authors: Chei Won Kim, Ji Sun Park, Se Hwan Oh, Jae-Hyung Park, Hyun-Ik Shim, Jae Woong Yoon, Jin Seok Park, Seong Bin Hong, Jun Mi Kim, Trong Binh Le, Jin Woo Lee
Journal: Clinical and Molecular Hepatology (2016)

Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well. Keywords: Iodine-131; Drug-induced liver injury (DILI); Corticosteroid