tbuckley/cabot-search huggingface dataset:
Polo-like Kinase 1 Is Involved in Invasion through Extracellular Matrix
Authors: Aylin Rizki, Joni D. Mott, Mina J. Bissell
Journal: Cancer Research (2007)

Abstract Polo-like kinase 1 (PLK1) has important functions in maintaining genome stability via its role in mitosis. Because PLK1 is up-regulated in many invasive carcinomas, we asked whether it may also play a role in acquisition of invasiveness, a crucial step in transition to malignancy. In a model of metaplastic basal-like breast carcinoma progression, we found that PLK1 expression is necessary but not sufficient to induce invasiveness through laminin-rich extracellular matrix. PLK1 mediates invasion via vimentin and β1 integrin, both of which are necessary. We observed that PLK1 phosphorylates vimentin on Ser82, which in turn regulates cell surface levels of β1 integrin. We found PLK1 to be also highly expressed in preinvasive in situ carcinomas of the breast. These results support a role for the involvement of PLK1 in the invasion process and point to this pathway as a potential therapeutic target for preinvasive and invasive breast carcinoma treatment. [Cancer Res 2007;67(23):11106–10]
Monitoring Chemotherapeutic Response by Hyperpolarized 13C-Fumarate MRS and Diffusion MRI
Authors: Lionel Mignion, Prasanta Dutta, Gary V. Martinez, Parastou Foroutan, Robert J. Gillies, Bénédicte F. Jordan
Journal: Cancer Research (2013)

Targeted chemotherapeutic agents often do not result in tumor shrinkage, so new biomarkers that correlate with clinical efficacy are needed. In this study, we investigated noninvasive imaging protocols to monitor responses to sorafenib, a multikinase inhibitor approved for treatment of renal cell and hepatocellular carcinoma. Healthy cells are impermeable to fumarate, so conversion of this metabolite to malate as detected by (13)C-magnetic resonance spectroscopy (MRS) has been suggested as one marker for cell death and treatment response in tumors. Diffusion MRI also has been suggested as a measure of therapy-induced cytotoxic edema because viable cells act as a diffusion barrier in tissue. For these reasons, we assessed sorafenib responses using hyperpolarized (13)C-fumarate, diffusion-weighted MRI (DW-MRI) in a xenograft model of human breast cancer in which daily administration of sorafenib was sufficient to stabilize tumor growth. We detected signals from fumarate and malate following intravenous administration of hyperpolarized fumarate with a progressive increase in the malate-to-fumarate (MA/FA) ratio at days 2 to 5 after sorafenib infusion. The apparent diffusion coefficient (ADC) measured by DW-MRI increased in the treated group consistent with cytotoxic edema. However, the MA/FA ratio was a more sensitive marker of therapeutic response than ADC, with 2.8-fold versus 1.3-fold changes, respectively, by day 5 of drug treatment. Histologic analyses confirmed cell death in the sorafenib-treated cohort. Notably, (13)C-pyruvate-to-lactate conversion was not affected by sorafenib in the breast cancer model examined. Our results illustrate how combining hyperpolarized substrates with DW-MRI can allow noninvasive monitoring of targeted therapeutic responses at relatively early times after drug administration.
Bronchial Hyperreactivity to Prostaglandin F2 and Histamine in Patients with Asthma
Authors: A. A. Mathe, P. Hedqvist, A. Holmgren, N. Svanborg
Journal: BMJ (1973)

The influence on airway conductance of inhaled aerosols of prostaglandin F<sub>2</sub>α (PGF<sub>2</sub>α), histamine, and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) was studied in 10 patients with spirometrically reversible bronchial asthma and in 10 healthy subjects with no history of lung disorder. Both groups responded with bronchoconstriction after inhalation of PGF<sub>2</sub>α but the asthmatic patients were about 8,000 times more sensitive to the compound than were the healthy controls. In the patients, but not in the controls, PGF<sub>2</sub>α often caused a long-standing decrease in airway conductance with symptoms resembling allergen-provoked asthmatic attacks. On the other hand, the patients showed less than a 10-fold increase in sensitivity to histamine, and the ratio of histamine: PGF<sub>2</sub>α doses causing a 50% decrease of airway conductance was 2·6:1 and 2,400:1 in controls and patients respectively. Inhalation of PGE<sub>2</sub> while moderately but consistently increasing airway conductance in controls, had a variable—occasionally slight bronchoconstrictive—effect in patients. The decrease in airway conductance by a given dose of PGF<sub>2</sub>α was little modified by the simultaneous inhalation of a 100-times higher PGE<sub>2</sub> dose. It is suggested that endogenous, locally formed PGF<sub>2</sub>α may play an important part in the pathogenesis of bronchial asthma.
Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG.
Authors: D Watkins, D S Rosenblatt
Journal: Journal of Clinical Investigation (1988)

A number of patients with megaloblastic anemia and homocystinuria associated with low levels of methylcobalamin synthesis in cultured cells have been recognized. Methionine biosynthesis by intact cells, as determined by incorporation of label from 5-[14C]methyl-tetrahydrofolate into acid-precipitable material, was deficient in cultured skin fibroblasts that were derived from all of these patients. In one group of patients, activity of the methylcobalamin-dependent enzyme, methionine synthase, in cell extracts was within the normal range when the enzyme was assayed under standard conditions. In a second group of patients, methionine synthase activity was decreased under the same assay conditions. Genetic complementation analysis demonstrated the existence of two complementation classes that corresponded to these two groups of patients. The designation cblE has previously been proposed for normal methionine synthase activity. We propose the designation cblG for the mutation in those patients with methylcobalamin deficiency and decreased synthase activity. The results of these studies suggest that the products of at least two loci are required for cobalamin-dependent methionine biosynthesis in mammalian cells.
FORMATION AND FUNCTIONAL SIGNIFICANCE OF A MOLECULAR COMPLEX DERIVED FROM THE SECOND AND THE FOURTH COMPONENT OF HUMAN COMPLEMENT
Authors: Hans J. Müller-Eberhard, Margaret J. Polley, Mary Ann Calcott
Journal: The Journal of Experimental Medicine (1967)

A functional unit of the human complement system has been delineated. It is composed of two subunits which are derived from the second (C'2) and from the fourth (C'4) component of complement. Purified C'2 and C'4 were found to interact in free solution and to form a reversible protein-protein complex. When acted upon by C'1 esterase in the presence of Mg ions, the reversible complex acquires stability and the ability to act enzymatically on the third component of complement. The trivial name C'3 convertase has been selected to denote the enzyme. Molecular weight determinations suggest that the entire C'4 molecule, but probably only a fragment of the C'2 molecule, are incorporated into C'3 convertase. Prior treatment of C'2 with iodine led to enhanced stability and activity of the enzyme. It was shown that the cell-bound form of C'3 convertase is cytolytically active and that the free enzyme is able to induce lysis from the fluid phase of erythrocytes from patients with paroxysmal nocturnal hemoglobinuria. Evidence was presented that action of C'3 convertase on C'3 results in fragmentation of the molecule.
The Diploma in Public Health
Authors: K. I. E. Macleod
Journal: BMJ (1953)

<h3>Objectives:</h3> Growing evidence shows that high levels of justice are beneficial for employee health, although biological mechanisms underlying this association are yet to be clarified. We aim to test whether high justice at work protects against metabolic syndrome. <h3>Methods:</h3> A prospective cohort study of 20 civil service departments in London (the Whitehall II study) including 6123 male and female British civil servants aged 35 to 55 years without prevalent CHD at baseline (1985-1990). Perceived justice at work was determined by means of questionnaire on two occasions between 1985 and 1990. Follow-up for metabolic syndrome and its components occurring from 1990 through 2004 was based on clinical assessments on three occasions over more than 18 years. <h3>Results:</h3> Cox proportional hazard models adjusted for age, ethnicity and employment grade showed that men who experienced a high level of justice at work had a lower risk of incident metabolic syndrome than employees with a low level of justice (hazard ratio 0.75; 95% confidence interval: 0.63-0.89). There was little evidence of an association between organizational justice and metabolic syndrome or its components in women (hazard ratio 0.88; 95%CI: 0.67-1.17). <h3>Conclusions:</h3> Our prospective findings provide evidence of an association between high levels of justice at work and the development of metabolic syndrome in men.
Severe Hyperpyrexia Due to Tranylcypromine-Amphetamine Toxicity
Authors: ISTVÁN KRISKÓ
Journal: Annals of Internal Medicine (1969)

Within hours after the ingestion of 10 mg tranylcypromine plus a capsule containing dextroamphetamine and amobarbital, a 41-year-old woman developed progressive agitation, hyperkinesis, fever (temperature to 109.4 F), coma, opisthotonus, and convulsions. The temperature, which was above 109 F for 30 min, was rapidly lowered by total immersion in an ice bath. With additional supportive measures the patient was responsive in 24 hr, and in 36 hr she was completely oriented. She was discharged without significant residua 20 days later. "Drug fever" of this magnitude resulting from the simultaneous ingestion of the monoamine oxidase inhibitor, tranylcypromine, and dextroamphetamine has not been reported previously.
Response to: 'The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region’ by Rinaudo-Gaujous<i>et al</i>
Authors: K A van Schie, M H Hart, E R de Groot, S Kruithof, L A Aarden, G J Wolbink, T Rispens
Journal: Annals of the Rheumatic Diseases (2015)

Response to: 'The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region' by Rinaudo-Gaujous et al Assessment of clinically relevant immunogenicity is a muchdebated topic.With respect to the neutralising capacity of antidrug antibodies (ADAs) to tumour necrosis factor (TNF) blockers, we recently demonstrated that the vast majority of antibodies in fact compete with TNF binding. 1 Therefore, we are pleased to find this notion further supported by the letter of Rinaudo-Gaujous et al. 2 The aim of our study was to quantify to which extent ADAs were neutralising.Using the TNF competition assay, we concluded that >90% (90.2-99.3%,n=34) of all ADAs could neutralise the drug.A strong correlation between ADA titres determined with the antigen binding test (which measures all ADA) and ADA titres determined with the WEHI bioassay (which measures neutralising antibodies) confirmed this conclusion.This neutralising effect of ADA was nicely reproduced by Rinaudo-Gaujous et al using an ADA ELISA and the reporter HEK-Dual TNF cell line, although only a qualitative correlation was shown.Furthermore, many studies over the last 10 years have demonstrated a link between antibodies to infliximab and loss of response in various patient groups, including Baert et al, 3 Bendtzen et al, 4 Pascual-Salcedo et al, 5 Wolbink et al 6 and Bito et al. 7Together with our conclusion that most ADAs bind infliximab on or close to the TNF binding site and thereby compete with TNF, these results imply that to measure the ADA titre the bioassays that are only sensitive to neutralising ADA will give virtually the same results as the assays that measure binding ADA.Our study found this high neutralising capacity not only for antibodies to infliximab but also for antibodies to adalimumab, certolizumab and golimumab.These results suggest an immunodominant role for the TNF binding site of anti-TNF therapeutic antibodies.As Rinaudo-Gaujous et al pointed out, the neutralising ADA level is an important measurement for drug activity.We would like to stress that by measuring the level of free or active drug also the direct impact of neutralising ADA will be measured since drug bound by neutralising ADA will remain undetected.][10] Monitoring primarily the level of infliximab would therefore be sufficient to determine whether the therapy is still effective or not.In case the drug levels are low or non-existent, additionally the ADA titre can be measured to ascertain if this is due to immunogenicity.
Altered permeability of the peritoneal membrane after using hypertonic peritoneal dialysis fluid
Authors: Lee W. Henderson, Karl D. Nolph
Journal: Journal of Clinical Investigation (1969)

Previous work has shown that use of hypertonic peritoneal dialysis fluid (7% glucose) results in ultrafiltration and enhanced urea transfer across the peritoneal membrane. Simultaneous creatinine studies showed a similar enhancement with hypertonic fluid which persisted in lesser degree during subsequent isotonic exchanges. The mechanism of solvent drag has been shown to contribute significantly to the increased urea removal with ultrafiltration. In the present study, the role of altered diffusive permeability of the peritoneal membrane as suggested by the creatinine data was evaluated as a possible additional mechanism. Hypertonic exchanges were bracketed by isotonic (1.5% glucose) exchanges during 11 studies in four patients. During six other studies in four patients, isotonic exchanges only were performed. A mathematical model for peritoneal solute transport by diffusion was developed and a method to distinguish alterations in peritoneal membrane permeability from changes in membrane area proposed. The method incorporates the determination and comparison of transport characteristics for two test solutes of widely different molecular weights. Alterations in inulin and urea transperitoneal transport characteristics in the above studies indicate a significant increase in membrane permeability after exposure to hypertonic solutions that persists during subsequent isotonic exchanges. Varying patterns of membrane area and permeability changes occurred during repeated exposure to only isotonic exchanges. The findings are discussed in regard to recent concepts of passive transcapillary transport.
The Future U.S. Healthcare System: Who Will Care for the Poor and Uninsured?
Authors: Arlene S. Bierman
Journal: Annals of Internal Medicine (1998)

Medical Writings15 May 1998The Future U.S. Healthcare System: Who Will Care for the Poor and Uninsured?Arlene S. Bierman, MD, MSArlene S. Bierman, MD, MSAgency for Health Care Policy and Research, Rockville, MarylandSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-10-199805150-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Altman SH, Reinhardt UW, Shields AE; eds. 426 pages. Chicago: Health Administration Pr; 1998. $44.00. ISBN 1567930670. Order phone 708-450-9952.Field of medicine: Health policy and health services research.Format: Softcover book.Audience: Physicians, health policy professionals, and health care administrators.Purpose: To provide background on the problem of caring for poor and uninsured persons in the United States and to provide policy recommendations.Content: The 22 chapters are divided into five sections. The first three sections give overviews of the literature on the uninsured, the growing challenges to the traditional safety net, and the effect of for-profit hospital conversions. ... Author, Article, and Disclosure InformationAffiliations: Agency for Health Care Policy and Research, Rockville, MarylandDisclaimer: The views given here are those of the author. No official endorsement from the Agency for Health Care Policy and Research or the Department of Health and Human Services is intended or should be inferred. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 1998Volume 128, Issue 10Page: 879-880KeywordsChildrenForecastingHealth careHealth care policyHealth insuranceHealth services researchPrevention, policy, and public healthRiversSafety ePublished: 15 August 2000 Issue Published: 15 May 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
THE RELATION OF THE PANCREAS TO DIABETES
Authors: JOSEPH H. PRATT
Journal: JAMA (1910)

Over two hundred years ago Conrad Brunner<sup>1</sup>showed by experiments on dogs that a large portion of the pancreas could be removed without affecting the health of the animals. Progress in the physiology of the pancreas was slow and as late as 1888 the conclusions reached by Martinotti<sup>2</sup>in his experimental studies published that year were those generally accepted. Martinotti asserted that after the complete extirpation of the pancreas no disturbance resulted either in the general condition or in the digestive functions. The dogs in fact gained in weight. Claude Bernard<sup>3</sup>had asserted that shutting off the pancreatic juice by injecting oil into the ducts under considerable pressure, caused a serious disturbance in the absorption of fat, but subsequent investigators were unable to confirm his observations. The idea that there was some relation between diabetes and disease of the pancreas was entertained by a number of clinicians,
Management of Life-threatening Asthmatic Attacks.
Authors: Carl E. Arbesman
Journal: Annals of Internal Medicine (1967)

s1 May 1967Management of Life-threatening Asthmatic Attacks.Carl E. Arbesman, M.D., F.A.C.P.Carl E. Arbesman, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1026_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe therapy of status asthmaticus is elaborated in some detail including the use of adequate hydration, bronchodilators, antibiotics, and corticosteroids. This is dealt with only briefly in introducing the rest of the discussion.When the patient in status asthmaticus does not respond to the above-mentioned therapy, the proper diagnosis and management become critical. Careful monitoring of the arterial blood gases, establishing an adequate airway, and the use of different types of mechanical ventilators are discussed in detail.Descriptions of the types of airways to be produced, the types of mechanical aids, nursing, and team care are emphasized in detail.It... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Buffalo, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1026-1026KeywordsAntibioticsBloodBronchodilatorsCorticosteroid therapyVentilators Issue Published: 1 May 1967 PDF DownloadLoading ...
Physiological and clinical assessment of the effect of the musculotropic agent mebeverine on the human colon.
Authors: A. M. Connell
Journal: BMJ (1965)

Folic-acid Deficiency-Read et al.BMEDICARNISHRNAI and all except 5 patients gained weight.The patients showed greater frequency of folic-acid deficiency than a group of aged control subjects, and their diets contained, prior to admission to the home, less folic acid, iron, protein, and total calories.The implications of these studies are discussed.We are indebted to Professor R. C. Wofinden and Dr. J. F. Skone, of the Department of Public Health, for their help in arranging this investigation, and
TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model
Authors: Yoko Yoshio, Masanobu Miyazaki, Katsushige Abe, Tomoya Nishino, Akira Furusu, Yohei Mizuta, Takashi Harada, Yoshiyuki Ozono, Takehiko Koji, Shigeru Kohno
Journal: Kidney International (2004)
Changed guidance on payment for study participants puts them at higher risk of harm, group says
Authors: M. McCarthy
Journal: BMJ (2013)

A change in a guidance document concerning payment for participating in research undermines protection for human participants, a US consumer advocacy group has said.1

At issue is how much study participants can be paid without causing them to accept risks that they wouldn’t otherwise have accepted.

Under current US policy, payment is allowed to remunerate participants for their time, inconvenience, and discomfort, for example, but should not be so large that it induces them to accept risks they wouldn’t accept if it were not for the money. The concern is that such payments could be used to exploit poor people who might agree to participate in high risk studies because of their need for money.

The changes that sparked the controversy appear in a document of frequently asked questions about informed consent, issued by the US Office for Human Research Protections (OHRP). …
siRNA and pharmacological inhibition of endocytic pathways to characterize the differential role of macropinocytosis and the actin cytoskeleton on cellular uptake of dextran and cationic cell penetrating peptides octaarginine (R8) and HIV-Tat
Authors: M. Al Soraj, L. He, K. Peynshaert, J. Cousaert, D. Vercauteren, K. Braeckmans, S.C. De Smedt, A.T. Jones
Journal: Journal of Controlled Release (2012)
Application of near infrared spectroscopy to the analysis and fast quality assessment of traditional Chinese medicinal products
Authors: Chao Zhang, Jinghua Su
Journal: Acta Pharmaceutica Sinica B (2014)

Near infrared spectroscopy (NIRS) has been widely applied in both qualitative and quantitative analysis. There is growing interest in its application to traditional Chinese medicine (TCM) and a review of recent developments in the field is timely. To present an overview of recent applications of NIRS to the identification, classification and analysis of TCM products, studies describing the application of NIRS to TCM products are classified into those involving qualitative and quantitative analysis. In addition, the application of NIRS to the detection of illegal additives and the rapid assessment of quality of TCMs by fast inspection are also described. This review covers over 100 studies emphasizing the application of NIRS in different fields. Furthermore, basic analytical principles and specific examples are used to illustrate the feasibility and effectiveness of NIRS in pattern identification. NIRS provides an effective and powerful tool for the qualitative and quantitative analysis of TCM products.