tbuckley/cabot-search huggingface dataset:
A Kinetic Threshold between Negative and Positive Selection Based on the Longevity of the T Cell Receptor–Ligand Complex
Authors: Calvin B. Williams, Deborah L. Engle, Gilbert J. Kersh, J. Michael White, Paul M. Allen
Journal: The Journal of Experimental Medicine (1999)

We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II– restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64–76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR–ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR–ligand complexes.
An unusual zoonosis
Authors: Janet Menage
Journal: BMJ (2005)

As a general practitioner and pet owner, I treated my scratching Abyssinian guinea pigs' nits with subcutaneous ivermectin. A few days later, I experienced intense pruritus of the forearms with raised papules surrounded by a histamine-like response. Assuming that the lesions were mosquito bites from warm, humid evening dog walks, I attempted to suppress the irritation with mometasone, but with only partial success. As the days progressed, excoriations developed, without a history of injury, that did …
Reversible Contraception for the 1980s
Authors: David A. Grimes
Journal: JAMA (1986)

EACH DAY, tens of millions of Americans swallow a pill, slide in a diaphragm, or slip on a condom to prevent unwanted pregnancies. These strategies are working, although not as well as they could. While rates of unwanted pregnancies have declined dramatically in recent years,<sup>1</sup>nonuse or inconsistent use of contraception, especially among sexually active teenagers,<sup>2</sup>persists. In general, fear of complications, not the complications themselves, is the most powerful deterrent to contraception.<sup>3</sup>Much of this fear is unwarranted, fueled in part by inaccurate or incomplete media coverage.<sup>4</sup>Although no new contraceptive chemical has been introduced in the United States since 1968,<sup>5</sup>the safety and acceptability of existing contraceptive methods have improved greatly. In this review, I will provide a brief clinical update on reversible contraception, including current use of contraception, the efficacy of various methods, the safety of these methods, and a brief overview
Abstract 4230: Anthocyanins from the fruit of Vitis coignetiae Pulliat exhibits anticancer effects on Hep 3B human hepatocelluar carcinoma cells xenografts in nude mice
Authors: Jing Nan Lu, Min Jeong Kim, Won Sup Lee, Jeong Won Yun, Dong Chul Kim, Yun Koung Lee, Jae-Hoon Jeong, Yung Hyun Choi, GonSup Kim, Chung Ho Ryu, Ock Jin Park, Sung Chul Shin
Journal: Cancer Research (2011)

Abstract Vitis coignetiae Pulliat (Meoru in Korea) has been used as a folk remedy for inflammatory diseases and cancers. Our previous in vitro study suggested that anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) should have anti-cancer activities through suppression of NF-κB. Before in vivo study, we also confirmed with Hep3B human hepatocellular carcinoma cells that AIMs suppressed NF-κB-regulated gene products. Here, we investigated their effects on NF-κB-regulated gene products and cellular responses in Hep3B cell-originated tumors in athymic nude mice. Hep3B cells (1 × 106 cells/0.1 mL) were subcutaneously injected into the left flank of twelve athymic (nu/nu) male nude mice, and then the nude mice were randomly divided into two groups with six animals each. The first group of animals received intraperitoneal injection of 100 AL of 1:10 ratio of DMSO and normal saline, whereas animals of the second group received intraperitoneal injection of AIMs (5 μg/g of animal in 100 AL of 1:10 ratio of DMSO and normal saline) daily. The AIMs suppressed the tumor growth compared to control. AIMs suppressed Ki67 expression and intratumoral vessel density on immunohistochemical staining. In addition, Western blot and immunohistochemical staining revealed AIMs suppressed the NF-KB activation and NF-KB-regulated protein levels such as COX-2, XIAP, MMP-9, VEGF and ICAM which are related to cancer cell proliferation, survival, invasion and angiogenesis in Hep3B cell-originated tumors in athymic nude mice. However, the expressions of some NF-KB-regulated proteins were not significantly suppressed. Taken together, this study indicates that the AIMs have anti-cancer effects on Hep3B cell xenografts at least in part through the inhibition of NF-κB activation and downstream proteins. This study provides evidence that AIMs might have anticancer effects on human hepatocellular carcinoma. [This study was supported by a grant from the National R&amp;D Program for Cancer Control, Ministry for Health, Welfare &amp; Family Affairs, Republic of Korea. (0820050).] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4230. doi:10.1158/1538-7445.AM2011-4230
Lymphangioleiomyomatosis: Cause of a Malignant Chylous Pleural Effusion
Authors: Izabela Malinowska-Kolodziej, Geraldine Finlay, Gregory Campbell, Maria L. Garcia-Moliner, Barbara Weinstein, Cheryl A. Doughty, Wei Qin, Catherine Butterfield, Sarah Short, Kuniaki Seyama, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2009)
Employees with epilepsy in the National Health Service.
Authors: J R Lisle, H A Waldron
Journal: BMJ (1986)

Les reponses a des questionnaires envoyes a 45 services de sante publique montrent que 0,2 a 5 employes/1000 sont atteints d'epilepsie. Certains emplois ne peuvent pas convenir a des malades epileptiques meme bien controles. Moyens d'ameliorer la situation en modifiant les emplois
Is prolonged lack of sleep associated with obesity?
Authors: F. P. Cappuccio, M. A. Miller
Journal: BMJ (2011)

Possibly, and it could have other effects on long term ill health

In the linked longitudinal study (doi:10.1136/bmj.d2712), Carter and colleagues assess the association between reduced sleep and differences in body composition and the risk of becoming overweight in young children.1

We spend about a third of our life asleep. We spend more time asleep as babies and children and then generally settle into a pattern of seven to eight hours a night. Sufficient sleep is necessary for optimal daytime performance and wellbeing, yet the amount of sleep that people get varies greatly.2 

The quantity and quality of sleep have shown secular trends alongside changes in modern society that require longer hours of work, more shift work, and “24/7” availability of commodities. These changes have reduced the average duration of sleep across westernised populations, with increased reporting of fatigue, tiredness, and excessive daytime sleepiness.2 This sleep curtailment has been attributed mainly to lifestyle changes.2 Too little sleep is associated with adverse health outcomes, including total mortality,3 stroke and coronary heart disease,4 type 2 diabetes,5 hypertension,6 respiratory disorders, poor self rated health,2 and obesity in adults and children.7

Obesity in childhood has now reached epidemic proportions and is a cause of psychosocial problems including low self esteem. It often continues into adulthood, where it causes major morbidity, disability, and premature death. Several studies have reported associations between short duration of sleep …
Drug companies monitor web chat for adverse reaction reports
Authors: Michael Cross
Journal: BMJ (2005)

Drug companies are harvesting comments posted on the internet about drug side effects using new computer technology. NetRank, a UK based internet consultancy, said this week that at least one “well known drug company” is using a product called i-reputation, which monitors the internet for postings about specific products.

Critics of the pharmaceutical industry expressed concern about the way the information might be used. The technology is based on a computer program developed for the mobile phone maker Motorola to track comments about its products in internet chat …
The Right Test: A Physician's Guide to Laboratory Medicine
Authors: David A. Horowitz
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes20 April 1999The Right Test: A Physician's Guide to Laboratory MedicineDavid A. Horowitz, MDDavid A. Horowitz, MDHospital of the University of Pennsylvania, Philadelphia, Pennsylvania. (Horowitz)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-8-199904200-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 3rd edition. Speicher CE. 350 pages. Philadelphia: WB Saunders; 1998. $29.95. ISBN 0721651232. Order phone 800-545-2522.Field of medicine: Laboratory medicine and primary care.Format: Softcover book.Audience: Health care providers and trainees who order laboratory and radiologic tests to assist in clinical decision making.Purpose: To guide the clinician in the appropriate use of available tests.Content: The introduction addresses the issue of limited resources for medical care and testing and contrasts this fiscal reality with the expanding array of available tests. It also discusses the use of evidence-based medicine as a launching point for ordering confirmatory and diagnostic ... Author, Article, and Disclosure InformationAffiliations: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. (Horowitz) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 April 1999Volume 130, Issue 8Page: 703KeywordsClinical laboratoriesDecision makingEvidence based medicineHealth care providersLaboratory testsResearch laboratoriesSoftware toolsSub-specialty care ePublished: 15 August 2000 Issue Published: 20 April 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Chloroform: An EPA test case.
Authors: C W Schmidt
Journal: Environmental Health Perspectives (1999)

In March 1998, the U.S. Environmental Protection Agency (EPA) published a proposal to raise the drinking water maximum contaminant level goal (MCLG) for chloroform, a suspected human carcinogen, from zero to 300 parts per billion. The proposal marked a departure from the agency's traditional reliance on linear dose-response models in performing risk assessment, and reflected the new thinking contained in the 1996 draft update to the agency's cancer risk assessment guidelines. The updated guidelines emphasize mechanisms of action and descriptions of the conditions under which carcinogenic hazards are likely to be expressed.
Sensitization of IFN-γ Jak-STAT signaling during macrophage activation
Authors: Xiaoyu Hu, Carmen Herrero, Wai-Ping Li, Taras T. Antoniv, Erik Falck-Pedersen, Alisa E. Koch, James M. Woods, G. Kenneth Haines, Lionel B. Ivashkiv
Journal: Nature Immunology (2002)
Histone Deacetylase Inhibitors and 15-Deoxy-Δ12,14-Prostaglandin J2 Synergistically Induce Apoptosis
Authors: Makoto Koyama, Yasuyuki Izutani, Ahmed E. Goda, Taka-aki Matsui, Mano Horinaka, Mitsuhiro Tomosugi, Jun Fujiwara, Yoshitaka Nakamura, Miki Wakada, Shingo Yogosawa, Yoshihiro Sowa, Toshiyuki Sakai
Journal: Clinical Cancer Research (2010)

The clinically relevant histone deacetylase inhibitors (HDI) valproic acid (VPA) and suberoylanilide hydroxamic acid exert variable antitumor activities but increase therapeutic efficacy when combined with other agents. The natural endogenous ligand of peroxisome proliferator-activated receptor gamma 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a potent antineoplastic agent. Therefore, we investigated whether these HDIs in combination with 15d-PGJ(2) could show synergistic antitumor activity in colon cancer DLD-1 cells.Cell viability was determined using a Cell Counting Kit-8 assay. Apoptosis and reactive oxygen species (ROS) generation were determined using flow cytometry analysis. Western blotting and real-time reverse transcription-PCR analysis were carried out to investigate the expression of apoptosis-related molecules. Mice bearing DLD-1 xenograft were divided into four groups (n = 5) and injected everyday (i.p.) with diluent, VPA (100 mg/kg), 15d-PGJ(2) (5 mg/kg), or a combination for 25 days.HDI/15d-PGJ(2) cotreatments synergistically induced cell death through caspase-dependent apoptosis in DLD-1 cells. Moreover, HDIs/15d-PGJ(2) caused histone deacetylase inhibition, leading to subsequent ROS generation and endoplasmic reticulum stress to decrease the expression of antiapoptotic molecules Bcl-X(L) and XIAP and to increase that of proapoptotic molecules CAAT/enhancer binding protein homologous protein and death receptor 5. Additionally, VPA/15d-PGJ(2) cotreatment induced ROS-dependent apoptosis in other malignant tumor cells and was more effective than a VPA or 15d-PGJ(2) monotherapy in vivo.Cotreatments with the clinically relevant HDIs and the endogenous peroxisome proliferator-activated receptor gamma ligand 15d-PGJ(2) are promising for the treatment of a broad spectrum of malignant tumors.
Group B streptococcal sepsis in the piglet: effects of fluid therapy on venous return, organ edema, and organ blood flow.
Authors: M A Bressack, N S Morton, J Hortop
Journal: Circulation Research (1987)

We investigated the physiologic effects of normal saline versus 5% albuminated saline fluid resuscitation on 10-12-day-old piglets infected with group B streptococci for four hours. After intravenously receiving 1 X 10(10) bacteria/kg over 45 minutes, one group was untreated while the two fluid-treated groups received enough intravenous fluid to maintain the baseline cardiac output. An increase in the resistance to venous blood return was the major limitation to cardiac output. The resistance nearly quadrupled in the untreated piglets as shown by a 50% decrease in cardiac output with a nearly doubling of the driving pressure for venous return (mean circulatory pressure was normal and atrial pressures decreased by 70%). In both fluid-treated groups, resistance doubled as shown by an unchanged cardiac output with a doubling of the driving pressure (mean circulatory pressure increased by 50%) and atrial pressures remained at baseline). Blood volume was 9% below control in the untreated group and 13% above control in both fluid-treated groups. Much more crystalloid (155 ml/kg) than colloid (58 ml/kg) was necessary to maintain baseline cardiac output; this resulted in a 36% decrease in the plasma protein oncotic pressure of the former group and a 15% increase in the oncotic pressure of the latter group. Organ edema formation (ileum, pancreas, kidney, adrenal gland, lung) occurred only in the saline-treated animals. We conclude that increased resistance to venous return was the primary cause of shock in our model and that this can be effectively treated by giving enough intravenous fluid to elevate the mean circulatory pressure. However, if the plasma protein oncotic pressure is also lowered (saline group), organ edema results.
Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis
Authors: Azra Raza, Suneel Mundle, Amna Iftikhar, Stephanie Gregory, Bridget Marcus, Zaineb Khan, Sairah Alvi, Vilasini Shetty, Sherry Dameron, Vonda Wright, Solomon Adler, Jerome M. Loew, Susan Shott, Syed Nadir Ali, Harvey Preisler
Journal: American Journal of Hematology (1995)

Abstract Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end‐labeling of DNA directly from BM biopsies, which were simultaneously double‐labeled for proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S‐phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function. ©1995 Wiley‐Liss, Inc.
Foreign Bodies Removed from Abdomen.
Authors: William A. Gott
Journal: JAMA (1898)

Viroqua, Wis., April 19, 1898. <h3>Dr. M. R. Gage, Phoenix, Ariz., Dear Doctor:</h3> —Aware of the interest you have hitherto taken in the case of Miss Clara Condit (the late Capt. Condit's daughter), now an inmate of our County Asylum, I have thought best to put you in possession of some facts of late development regarding the unfortunate woman which, I think, will prove of interest to you. Saturday morning last I was requested by Dr. Morley of this place, physician in charge at the asylum, to see with him the patient referred to. The nurse in charge informed us that early that morning the patient called her attention to a small swelling in her right upper groin which was painful and interfered with her movements more or less, and also reiterated the statement made a month or six weeks before that she had swallowed two teaspoons, a table knife,
New bill will regulate the retention of tissue
Authors: C. Dyer
Journal: BMJ (2003)

The Human Tissue Bill will make consent “the fundamental principle underpinning the lawful removal, retention and use of human bodies, body parts, organs and tissue.”

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Candles at church service representing the children whose organs were retained by Alder Hey Children's

Credit: PHIL NOBLE/PA

The bill comes after the discovery—during the inquiry into high mortality among babies undergoing heart surgery at Bristol Royal …

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Abstract 2298: ck2-Dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B-isoform-specific target gene expression in breast cancer cells
Authors: Christy R. Hagan, Tarah Regan, Gwen Dressing, Carol Lange
Journal: Cancer Research (2011)

Abstract Progesterone receptors (PR) are critical mediators of mammary gland development and contribute to breast cancer progression. Progestin-induced rapid activation of cytoplasmic protein kinases leads to selective regulation of growth-promoting genes by phospho-PR species. Herein, we show that phosphorylation of PR Ser81 is ck2-dependent and progestin-regulated in intact cells, but also occurs in the absence of PR ligands, when cells enter the G1/S phase of the cell cycle. T47D breast cancer cells stably expressing a PR-B mutant that cannot be phosphorylated at Ser81 (S81A) formed fewer soft agar colonies. Regulation of selected genes by PR-B, but not PR-A, also required Ser81 phosphorylation for basal and/or progestin-regulated (BIRC3, HSD11β2, and HbEGF) expression. Additionally, wt PR-B, but not S81A mutant PR, was robustly recruited to a PRE-containing transcriptional enhancer region of BIRC3; abundant ck2 also associated with this region in cells expressing wt but not S81A PR. We conclude that phospho-Ser81 PR provides a platform for ck2 recruitment and regulation of selected PR-B target genes. Understanding how PR functions in the context of high kinase activities characteristic of breast cancer is critical to understanding the basis of tumor-specific changes in gene expression and will speed the development of highly selective treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2298. doi:10.1158/1538-7445.AM2011-2298
Hospital doctor's responsibility for prescribing.
Authors: J S Wright, R J Bibby, P J Hayes, M S Hendy, P E Isaacs, F I Lee, J D MacKay, J F O'Reilly
Journal: BMJ (1987)

<b>Introduction:</b> The Region of North Denmark has a high incidence of malignant mesothelioma (MM) of 6.2/100.000 for men and 1/100.000 for women mainly due to large-scale use of chrysotile asbestos. <b>Aims:</b> The aim of the study is to investigate gender differences in asbestos exposure and disease location for MM. <b>Methods:</b> Histopathological samples of 236 men and 91 women with MM were retrieved from the Institute of Pathology, Aalborg University Hospital. Asbestos exposure information was harvested from medical records and Danish registries. Asbestos exposure type was categorized as <i>primary</i>, for asbestos workers; <i>domestic</i>, referring to patients living with an asbestos worker; <i>environmental</i>, defined as living or working within 10.000 meters from asbestos emitting location; <i>unknown</i>, where no source of asbestos exposure could be identified. MM location was classified as pleural (MPM) or peritoneal (MAM) disease. Paired T-tests were used to compare the groups (men versus women). <b>Results:</b> Primary asbestos exposure was observed in 88% of men and 9% of women. Significantly more women than men had secondary (domestic, environmental or both) asbestos exposure (P&lt; 0.00001). MAM presented in 18% of the female and 4% of the male patients (P=0.0009) (Figure 1a&amp;b). <b>Conclusions:</b> The main cause of MM in men seems to be primary, in women secondary asbestos exposure. MAM was significantly more frequent in women. Both findings need further study.