tbuckley/cabot-search huggingface dataset:
Structure-activity relationships for xenobiotic transport substrates and inhibitory ligands of P-glycoprotein.
Authors: L J Bain, J B McLachlan, G A LeBlanc
Journal: Environmental Health Perspectives (1997)

The multixenobiotic resistance phenotype is characterized by the reduced accumulation of xenobiotics by cells or organisms due to increased efflux of the compounds by P-glycoprotein (P-gp) or related transporters. An extensive xenobiotic database, consisting primarily of pesticides, was utilized in this study to identify molecular characteristics that render a xenobiotic susceptible to transport by or inhibition of P-gp. Transport substrates were differentiated by several molecular size/shape parameters, lipophilicity, and hydrogen bonding potential. Electrostatic features differentiated inhibitory ligands from compounds not catagorized as transport substrates and that did no interact with P-gp. A two-tiered system was developed using the derived structure-activity relationships to identify P-gp transport substrates and inhibitory ligands. Prediction accuracy of the approach was 82%. We then validated the system using six additional pesticides of which tow were predicted to be P-gp inhibitors and four were predicted to be noninteractors, based upon the structure-activity analyses. Experimental determinations using cells transfected with the human MDR1 gene demonstrated that five of the six pesticides were properly catagorized by the structure-activity analyses (83% accuracy). Finally, structure-activity analyses revealed that among P-gp inhibitors, relative inhibitory potency can be predicted based upon the surface area or volume of the compound. These results demonstrate that P-gp transport substrates and inhibitory ligands can be distinguished using molecular characteristics. Molecular characteristics of transport substrates suggest that P-gp may function in the elimination of hydroxylated metabolites of xenobiotics.
An Audit and Comparative Analysis of the Kidney Transplantation Programme in Burma
Authors: N.N.K.S. Thin
Journal: International Journal of Surgery (2004)

The first renal transplant operation to be carried out by a Burmese transplant team was undertaken at the Yangon General Hospital, Burma on the 8th of May 1997. Since then 21 further kidney transplantations have been performed in hospitals in Yangon (Rangoon) and Mandalay. Burma was renamed as Myanmar in 1989. The Myanmar national renal transplant programme was introduced and performed as a special project organised by the Ministry of Health. Unfortunately little is known in other countries about the programme's development or the outcomes of the patients treated.In August 2003, the author visited Myanmar with the intention of evaluating the progress that this programme had made in the last six years.Retrospective data concerning all recipients and donors involved in the Myanmar renal transplant programme was obtained from the patient databases and through personal meetings with staff at the Urology and Nephrology units in Yangon and Mandalay.All 22 cases were blood related living donor transplants. There were 14 males and 8 female donors with a mean age of 36.5 (28-53) years and 13 male and 9 female recipients with a mean age of 38.3 (19-60) years included in the programme. There was a 100% survival rate of all 22 donors and a 95% (n = 21) recipient survival rate recorded in the programme up to September 2003. The one-year graft survival rate is 95% (n = 21) and the overall graft survival rate until September 2003 is 91% (n = 20), the mean follow-up was 2 years and 4 months.The success of this programme is extremely impressive considering the turbulent socio-economic climate in this developing country. The next steps for Myanmar are to organise a domestic registry system for transplants, the organisation of personnel to take responsibility for data collection, distribution and greater communication with other transplant units.
L-Tryptophan Ingestion Associated with Eosinophilic Fasciitis but Not Progressive Systemic Sclerosis
Authors: Bruce Freundlich
Journal: Annals of Internal Medicine (1990)

Objective: To assess the use of L-tryptophan by patients with eosinophilic fasciitis and compare this with its use by patients with progressive systemic sclerosis (scleroderma). Design: Retrospective and prospective analysis. Six patients with eosinophilic fasciitis were identified retrospectively and two prospectively. Retrospective identification of patients was done by questioning hospital-affiliated rheumatologists and dermatologists and by searching the hospital dermatopathology database. The patients with scleroderma or morphea were prospectively identified by questioning consecutive office patients with these established diagnoses. Setting: University of Pennsylvania rheumatology and dermatology practices. Patients: Eight patients with eosinophilic fasciitis; 40 consecutive patients with scleroderma (27 with diffuse cutaneous and 13, limited cutaneous disease); 3 patients with morphea. Results of Data Analysis: All eight patients with eosinophilic fasciitis had taken L-tryptophan before the onset of their disease. All had myalgias and high peripheral eosinophil counts (most > 5000 cells/mm3). Only 1 of 40 patients with scleroderma (no patients with morphea) had used L-Tryptophan preceding illness (P < 0.001 compared with eosinophilic fasciitis). Six patients with eosinophilic fasciitis had taken L-tryptophan for less than 8 months. One patient had taken it for 9 years before developing skin induration. Two patients were newly identified as having hypothyroidism; two developed neuropathy; and two had severe flexion contractures (several occurring in areas without skin induration). Five patients had low-titer antinuclear antibodies, indicating a possible autoimmune process. Most patients had only a partial response to systemic corticosteroid therapy. One patient has had important disease regression in response to isotretenoin therapy that was evident even while she continued to take L-tryptophan. Conclusions: L-Tryptophan use can lead to eosinophilic fasciitis whereas it does not appear to cause classic scleroderma. The disease process does not automatically remit after discontinuation of L-tryptophan-containing products.
THE HEMATOCRIT OF THE LESSER CIRCULATION IN MAN 12
Authors: Lawrence S. Lilienfield, Renato D. Kovach, Paul A. Marks, Lee M. Hershenson, Gerald P. Rodnan, Franklin G. Ebaugh, Edward D. Freis
Journal: Journal of Clinical Investigation (1956)

A discrepancy appears to exist between total blood volume as calculated from albumin space and large vessel hematocrit, and total blood volume as calculated from red cell volume and this hematocrit (1, 2).The hematocrit as measured on arterial or venous blood indicates a ratio of red cell volume to plasma volume that is higher than the total body red cell volume to total body plasma volume ratio.Fahraeus (1) in 1921 performed experiments with blood flowing through fine glass capillaries in which he demonstrated a lower hematocrit in the fine capillaries than in the larger entrance or exit vessels.It was postulated that this phenomenon was due to laminar flow with axial streaming of red cells and consequent excess of plasma.Hence, the concept of a "small vessel or capillary hematocrit" was conceived.Freis, Stanton and Emerson (3), using T-1824 dye and differential agglutination of red cells (Ashby technique), studied the transit times of plasma and red cells through the human forearm and found a more rapid circulation for red cells than for plasma.Lawson, Overbey, Moore and Shadle (4) studied the pulmonary circulation in dogs with T-1824 dye and p82 tagged red cells.These authors concluded that the hematocrit of the pulmonary capillaries was much lower than '
Does evidence from ethology support bicoded cognitive maps?
Authors: Shane Zappettini, Colin Allen
Journal: Behavioral and Brain Sciences (2013)

Abstract The presumption that navigation requires a cognitive map leads to its conception as an abstract computational problem. Instead of loading the question in favor of an inquiry into the metric structure and evolutionary origin of cognitive maps, the task should first be to establish that a map-like representation actually is operative in real animals navigating real environments.
Autoantibodies, autoimmune disease, and the birth of immune diagnostics
Authors: Eng M. Tan
Journal: Journal of Clinical Investigation (2012)

The appearance of autoantibody to DNA followed sequentially by the disappearance of anti-DNA and appearance of DNA antigen in a patient with systemic lupus erythematosus demonstrated that autoantibodies participate in immune complex–mediated pathogenesis. Continuing studies showed that autoantibodies are also useful biomarkers in clinical diagnosis and important reagents for elucidating the structure and function of intracellular proteins in cell biology. Recently, autoantibodies to tumor-associated antigens have been identified in cancer, and these findings have expanded the field of cancer immunodiagnostics.
Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children
Authors: G. L. Piacentini, D. G. Peroni, A. Bodini, E. Bonafiglia, E. Rigotti, E. Baraldi, A. H. Liu, A. L. Boner
Journal: Allergy (2009)

Background: The Childhood Asthma Control Test (C‐ACT) has been proposed as a tool in assessing the level of disease control in asthmatic children. To evaluate the position of C‐ACT in the clinical management of asthmatic children, in relationship to the level of airway inflammation as assessed by fractional exhaled nitric oxide (FeNO) and with lung function. Methods: A total of 200 asthmatic children were included in the study: 47 children with newly diagnosed asthma (‘New’) and without any regular controller therapy; and 153 children with previously diagnosed asthma, treated according to GINA guidelines, and evaluated during a scheduled follow‐up visit (‘Follow‐up’). Childhood Asthma Control Test, FeNO and lung function [forced expiratory volume 1 (FEV1) and forced vital capacity (FVC)] were evaluated. Results: In New vs Follow‐up participants, C‐ACT score ( P &lt; 0.001), FVC ( P &lt; 0.005) and FEV1 ( P &lt; 0.05) were significantly lower, and FeNO ( P = 0.011) were significantly higher. In New, but not in Follow‐up participants, significant correlations were observed between C‐ACT score and FeNO ( r = −0.51; P &lt; 0.001), FEV1 ( r = 0.34; P = 0.022) and FEV1/FVC ( r = 0.32; P = 0.03). This lack of correlation in Follow‐up visits seemed attributable to dissociation between inadequately controlled asthma by C‐ACT ratings with normalization of other measures such as FeNO levels. Conclusions: This study confirms and expands the concept that C‐ACT is complementary to, but not a substitute for, other markers of disease control in asthmatic children, especially in the context of follow‐up visits.
The Dirty War Index: A Public Health and Human Rights Tool for Examining and Monitoring Armed Conflict Outcomes
Authors: Madelyn Hsiao-Rei Hicks, Michael Spagat
Journal: PLoS Medicine (2008)

Madelyn Hsiao-Rei Hicks and Michael Spagat introduce the "Dirty War Index," a public health tool that identifies rates of undesirable or prohibited war outcomes inflicted on populations during armed conflict.
The mass uptake of cholesterol ester from low density lipoproteins by cultured smooth muscle and adventitial cells of human aortas.
Authors: S S Alam, K A Solen, D L Layman, M C Riddle, W E Connor
Journal: Circulation Research (1980)

Cultured human smooth muscle and adventitial cells were incubated with human serum and low density lipoprotein (LDL) to study the uptake and accumulation of cholesterol ester from exogenous LDL. The cellular total cholesterol varied with the amount of LDL cholesterol in the medium. The cholesterol ester content increased 4-fold after 2 hours of incubation. A 6-fold rise occurred by 24 hours and continued to 72 hours. The cholesterol ester of the adventitial cells was markedly depleted by incubation with abetalipoproteinemic serum or with a lipid-depleted plasma fraction. By the use of 14C-labeled LDL free cholesterol in the incubation medium, we calculated that some 70-80% of the total accumulated cholesterol ester after 24 hours of incubation was derived from LDL cholesterol ester, and only 20-30% was synthesized by the cells. These studies demonstrated conclusively that human cells greatly increase their cholesterol ester mass after incubation with LDL.
Effect of Work-to-Contract on Accident and Emergency Departments
Authors: J. K. Gosnold
Journal: BMJ (1975)

Change of Heart?SIR,-I would be grateful if I might make a small but important point.Your leading article (3 May, p. 240) suggests that the C.C.H.M.S. negotiators sensed that "Mrs.Castle seemed to have had a change of heart."I doubt very much that this is true and I think it would be more accurate to say that the negotiators observed a definite change in the Secretary of State's negotiating position and attitude.I apologize if I appear to be pedantic, but there lies herein an important distinc- ,tion which I feel must be made and re- corded.It was undoubtedly the significant changes in her negotiating posittion which led us to support the lifting of sanctions raither than some vague hope that there had been a sudden fundamental "change of heart."-Iam, etc.,
The Western Medical Tradition: 1800 to 2000
Authors: Russell C. Maulitz
Journal: Annals of Internal Medicine (2007)

Medical Writings: Book Notes15 May 2007The Western Medical Tradition: 1800 to 2000Russell C. Maulitz, MD, PhDRussell C. Maulitz, MD, PhDFrom CHI Systems Inc. and Drexel University College of Medicine, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-146-10-200705150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Bynum WF, Hardy A, Jacyna S, Lawrence C, Tansey EM, eds. 628 pages. New York: Cambridge Univ Pr; 2006. $29.99. ISBN 0521475651. Order at www.cambridge.org/us.Field of medicine: History of medicine.Format: Softcover book.Audience: Historians of science and medicine and physicians and general readers interested in Western medicine over the past 200 years.Purpose: To provide a new account of Western medicine over the past 200 years, written by leading experts who not only describe the most important people, events, and transformations but also give explanations for why medicine developed as it did.Content: No one has produced a ... Author, Article, and Disclosure InformationAffiliations: From CHI Systems Inc. and Drexel University College of Medicine, Philadelphia, Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 2007Volume 146, Issue 10Page: 760KeywordsGraduate medical educationHealth careHistory of medicineMedical ethics, humanities, and educationResearch laboratoriesSoftware toolsUndergraduates ePublished: 15 May 2007 Issue Published: 15 May 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Short-term variability of pulse rate and blood pressure in cardiac surgery patients
Authors: D. E. M. TAYLOR, J. S. WHAMOND, D. J. HITCHINGS, M. HULLINGER, D. BEGG
Journal: Cardiovascular Research (1975)

The magnitude and mathematical nature of short-term variations of pulse rate and mean arterial blood pressure has been studied in 27 post-operative cardiac surgical patients over a continuous period of 200 min in each case. Similar variability was observed in all patients. Short-term variations were composed predominantly of a series of rhythmic changes ranging from one synchronous with respiration to others between 2 and 5 min in cycle length. There was consistent variance of the beat-by-beat values for both variables about a continuously updating 5 min mean. The average standard deviation was 3.75 beats/min for pulse rate and 0.48 kPa (3.64 mm Hg) for mean arterial blood pressure. For both variables the distribution about the 5-min mean did not differ significantly from a normal distribution in 50 out of the 54 records. These findings have implications for the reproducibility of current methods of estimating mean pulse rate and blood pressure, and the change necessary before two estimates may be regarded as significantly different. The results are applicable both to the interpretation of Ward Charts by medical staff and to automated monitoring systems.
Air Force School Celebrates "Supporting the Flier"
Authors: Phil Gunby
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 4016: Rapamycin-resistant HIF-1α expression in hepatocellular carcinoma (HCC) cells and high sensitivity of endothelial cells within HCC tissues to rapamycin.
Authors: Hiroki Tanaka, Masahiro Yamamoto, Masaaki Miyakoshi, Katsuhiro Ogawa
Journal: Cancer Research (2013)

Abstract HIF-1 plays a pivotal role in cancer development via cellular growth,proliferation, survival, metabolism and angiogenesis. High expression of HIF-1α, a regulatory component of HIF-1, in cancer cells is due to increased synthesis of HIF-1α via the increased translation of HIF-1α mRNA under the influence of activated mTORC1 signaling as well as decreased HIF-1α degradation that is either on oxygen-dependent or independent mechanism. In mouse hepatocarcinogenesis, our previous data demonstrated that HIF-1α is overexpressed depending on the PI3K-Akt pathway from earliest stage and that HIF-1α knockdown by using siRNA resulted in marked growth retardation and cell death in HCC cells. We here demonstrated that Akt, 4E binding protein 1 (4EBP1) and p70 ribosomal protein S6 kinase (S6K) were hyperphosphorylated in mouse hepatic tumors and HCC cells, indicating that the PI3K-Akt-mTORC1 pathway was activated. However, although rapamycin, an inhibitor of mTORC1, effectively suppressed phosphorylation of 4EBP1 and S6K in HCC cells, HCC cells were resistant to rapamycin where HIF-1α continued to be expressed during rapamycin treatment. This HIF-1α expression was due to de novo synthesis of HIF-1α during rapamycin treatment as well as HIF-1α stabilization due to binding of HIF-1α to HSP90 that was constitutively over-expressed in the HCC cells. On the other hand, rapamycin induced extensive hemorrhagic necrosis in HCC tissues in vivo but not in normal liver or adenomas (benign lesions). Phosphorylated ribosome protein subunit 6 (rps6), the downstream phosphorylation target of mTORC1-S6K pathway, was specifically detected in the endothelial cells within HCCs but not those in normal liver or adenomas. Furthermore, rapamycin decreased proliferation of endothelial cells in vitro, reducing HIF-1α expression together with the decreased 4EBP and S6K phosphorylation, indicating that the endothelial cells within HCCs were especially sensitive to rapamycin. Dual treatment with inhibitors for mTOR and HSP90, therefore, could target both HCC cells and endothelial cells within HCCs, which might be an effective therapy for HCCs. Citation Format: Hiroki Tanaka, Masahiro Yamamoto, Masaaki Miyakoshi, Katsuhiro Ogawa. Rapamycin-resistant HIF-1α expression in hepatocellular carcinoma (HCC) cells and high sensitivity of endothelial cells within HCC tissues to rapamycin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4016. doi:10.1158/1538-7445.AM2013-4016
Hypereosinophilia associated with cardiac rhabdomyosarcoma
Authors: Vincent Lo Re, Kevin R. Fox, Victor A. Ferrari, Craig H. Scott, Plamen M. Kossev, Jay R. Kostman
Journal: American Journal of Hematology (2003)

Hypereosinophilia, defined as an absolute eosinophil count exceeding 1,500/mm(3), is caused by a limited number of disorders. Its association with malignancy is a rare occurrence that typically denotes extensive metastasis and a poor prognosis. Several theories have been proposed to explain the hypereosinophilia associated with malignancy, focusing on the production of eosinophilopoietic cytokines by tumors. We describe a patient with hypereosinophilia associated with a cardiac rhabdomyosarcoma, review the etiologies of hypereosinophilia, and discuss the possible mechanisms.
Emergency contraception approved in the US
Authors: T. Rutter
Journal: BMJ (1998)

The Food and Drug Administration has approved a special kit for emergency contraception in a move that campaigners hope will cut the number of unwanted pregnancies in the United States.

Although certain oral contraceptives can currently be used “off label” for postcoital prevention of pregnancy, this is the first time a specific combination of ethinyl oestradiol and levo-norgestrel has been approved for postcoital …
Echocardiographic Findings in Autosomal Dominant Polycystic Kidney Disease
Authors: K F Hossack, C L Leddy, A M Johnson, R W Schrier, P A Gabow
Journal: New England Journal of Medicine (1988)

Echocardiography, including Doppler analysis, was performed to assess the prevalence of cardiac abnormalities in 163 patients with autosomal dominant polycystic kidney disease, 130 unaffected family members, and 100 control subjects. In these three groups, the prevalence of mitral-valve prolapse was 26, 14, and 2 percent, respectively (P less than 0.0005). A higher prevalence of mitral incompetence (31, 14, and 9 percent, respectively; P less than 0.005), aortic incompetence (8, 3, and 1 percent, respectively; P less than 0.05), tricuspid incompetence (15, 7, and 4 percent, respectively; P less than 0.02), and tricuspid-valve prolapse (6, 2, and 0 percent, respectively; P less than 0.02) was also found in the patients with polycystic kidney disease. These findings reflect the systemic nature of polycystic kidney disease and support the hypothesis that the disorder involves a defect in the extracellular matrix and the cardiac abnormalities are an expression of that defect.
THE NUMERICAL LAWS GOVERNING THE RATE OF EXCRETION OF UREA AND CHLORIDES IN MAN
Authors: Franklin C. McLean
Journal: The Journal of Experimental Medicine (1915)

A method of measuring the rate of excretion of urea, in terms of the normal, as presented in a preceding paper, has been applied to the study of diseased conditions and of the action of drugs. Simultaneous observations on chloride excretion have been made by comparing the concentration of chlorides actually found in the plasma with the theoretical amount, calculated from the rate of excretion. Observations made in this way have been found applicable to the study of various diseased conditions.