tbuckley/cabot-search huggingface dataset:
Nurses could halve GP workload
Authors: R. Huddart
Journal: BMJ (1996)

novel treatments in children with acute life threatening disease might expect parents to agree to anything that might increase their child's chance of survival.Our experience shows that this is not true in all cases.Most local research ethics committees are now moving towards asking for reports of trials they have approved.It is rare, however, for them to ask about refusals to par- ticipate.Reports of trials to the committees and for publication should routinely state the proportion of people who refuse to participate and the reasons for this.This information may suggest whether patients are being properly informed, may help with study design, and might also be a means of detecting scientific fraud.
Dual T cell receptor beta chain expression on human T lymphocytes.
Authors: F Davodeau, M A Peyrat, F Romagné, A Necker, M M Hallet, H Vié, M Bonneville
Journal: The Journal of Experimental Medicine (1995)

Allelic exclusion of lymphocyte antigen receptor chains has been hypothesized as a mechanism developed by the immune system to ensure efficient lymphocyte repertoire selection and tight control of lymphocyte specificity. It was effectively shown to be operative for both the immunoglobulin (Ig) and the T cell receptor (TCR) beta chain genes. Our present observations suggest that close to 1% of human T lymphocytes escape this allelic control, and express two surface TCR beta chains with distinct superantigenic reactivities. Since this high frequency of dual beta chain expressors did not result in any dramatic immune dysregulations, these results question the need for a mechanism ensuring clonal monospecificity through allelic exclusion.
In vitro effect of bile salts on rat liver plasma membrane, lipid fluidity, and ATPase activity
Authors: Bruce F. Scharschmidt, Emmet B. Keeffe, Donald A. Vessey, Nancy M. Blankenship, Robert K. Ockner
Journal: Hepatology (1981)

Considerable evidence suggests that liver plasma membrane (LPM) NaK-ATPase [(Na + + K + )-dependent adenosinetriphosphatase] and Mg-ATPase (Mg 2+ -dependent adenosinetriphosphatase) activity and lipid fluidity are important in liver cell functions such as bile formation. However, little is known regarding factors which might alter these membrane properties in vivo. Bile salts are actively concentrated by liver cells under normal conditions and reach even higher tissue concentrations in cholestasis. Since current methodology does not permit investigation of the effect of bile salts on LPM in vivo , we have examined the effects of bile salts in vitro on isolated rat LPM essentially free of organelle contamination and enriched 52.9-, 23.8-, and 27.8-fold in NaK-ATPase, 5′-nucleotidase, and alkaline phosphatase, respectively, compared with homogenate. We found that taurocholate (0.5 to 4.0 m M ), taurochenodeoxycholate (0.25 to 4.0 m M ), deoxycholate (0.25 to 4.0 m M ), but not dehydrocholate (0.25 to 4.0 m M ) caused immediate, concentration-dependent inhibition of LPM Mg- and NaK-ATPase which at low bile salt concentration (1.0 m M ) was reversible. By contrast, taurocholate (1 to 4 m M ) had no effect on LPM 5′-nucleotidase activity. Both 1 m M taurocholate and taurochenodeoxycholate caused a decrease in the apparent K m for ATP of NaK-ATPase, but not of Mg-ATPase, and 1 m M taurochenodeoxycholate caused no significant change in the activation of either Mg- or NaK-ATPase by cations. Finally, LPM lipid fluidity measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as a probe was reversibly increased by taurocholate, taurochenodeoxycholate, and deoxycholate, but not dehydrocholate; the effect of taurochenodeoxycholate on lipid fluidity was confirmed by electron spin resonance using 5-(2,2-dimethyl- N -oxyl-oxayalidine)-stearic acid as a probe. However, by both techniques, the effect of low concentrations of these bile salts on ATPase activity was independent of detectable changes in fluidity. These findings indicate that at concentrations comparable to those reported for liver tissue endogenous, micelle-forming bile salts reversibly inhibit LPM ATPases and reversibly increase LPM lipid fluidity in vitro ; these two effects being dissociable at low bile salt concentrations. It is possible that bile salts may have similar effects in vivo , particularly under cholestatic conditions.
Fixed-Effects Models and Diagnosing Psychiatric Disorders
Authors: Gerhard B. Holt
Journal: JAMA Psychiatry (2014)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
FUNCTION OF RETINOID NUCLEAR RECEPTORS: Lessons from Genetic and Pharmacological Dissections of the Retinoic Acid Signaling Pathway During Mouse Embryogenesis
Authors: Manuel Mark, Norbert B. Ghyselinck, Pierre Chambon
Journal: The Annual Review of Pharmacology and Toxicology (2005)

▪ Abstract Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular differentiation, and tissue homeostasis. The use of in vitro systems initially led to the identification of nuclear receptor RXR/RAR heterodimers as possible transducers of the RA signal. To unveil the physiological functions of RARs and RXRs, genetic and pharmacological studies have been performed in the mouse. Together, their results demonstrate that (a) RXR/RAR heterodimers in which RXR is either transcriptionally active or silent are involved in the transduction of the RA signal during prenatal development, (b) specific RXRα/RAR heterodimers are required at many distinct stages during early embryogenesis and organogenesis, (c) the physiological role of RA and its receptors cannot be extrapolated from teratogenesis studies using retinoids in excess. Additional cell type–restricted and temporally controlled somatic mutagenesis is required to determine the functions of RARs and RXRs during postnatal life.
Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans.
Authors: D S Goldstein, G Eisenhofer, R Stull, C J Folio, H R Keiser, I J Kopin
Journal: Journal of Clinical Investigation (1988)

We examined plasma levels of the sympathetic neurotransmitter norepinephrine (NE) and its deaminated metabolite dihydroxyphenylglycol (DHPG) during supine rest in healthy human subjects and in sympathectomized patients, during physiological (tilt) or pharmacological (yohimbine, clonidine) manipulations known to affect sympathetically mediated NE release, during blockade of neuronal uptake of NE (uptake-1) using desipramine, and during intravenous infusion of NE. Healthy subjects had a mean arteriovenous increment in plasma DHPG in the arm (10%, P less than 0.05), whereas sympathectomized patients had a mean arteriovenous decrement in DHPG in the affected limb (mean decrease 21%, P less than 0.05 compared with healthy subjects). Tilt and yohimbine, which stimulate, and clonidine, which inhibits, release of endogenous NE, produced highly correlated changes in plasma NE and DHPG (r = 0.94). Pretreatment with desipramine abolished DHPG responses to yohimbine while enhancing NE responses. To attain a given increase in plasma DHPG, about a tenfold larger increment in arterial NE was required during NE infusion than during release of endogenous NE. When plasma NE was markedly suppressed after administration of clonidine, plasma DHPG decreased to a plateau level of 700-800 pg/ml. The results indicate that (i) plasma DHPG in humans is derived mainly from sympathetic nerves; (ii) increments in plasma DHPG during stimulation of NE release result from uptake of NE into sympathetic nerve endings and subsequent intraneuronal conversion to DHPG; (iii) plasma DHPG under basal conditions probably is determined mainly by net leakage of NE into the axonal cytoplasm from storage vesicles; and (iv) increments in NE concentrations at neuronal uptake sites can be estimated by simultaneous measurements of DHPG and NE during NE infusion and NE release. Measurement of NE and DHPG provides unique clinical information about sympathetic function.
Age-Related Characteristics of Ambulatory Blood Pressure Load and Mean Blood Pressure in Normotensive Subjects
Authors: Prince K. Zachariah, Sheldon G. Sheps, Kent R. Bailey, Christine M. Wiltgen, Andrew G. Moore
Journal: JAMA (1991)

Ambulatory blood pressure monitoring has become increasingly popular for diagnosing and treating hypertension. However, data from normotensive subjects are needed for interpretation of hypertensive readings. Ambulatory blood pressure was monitored in 126 normotensive subjects (age range, 20 to 84 years). Mean systolic and diastolic blood pressure and blood pressure loads (percentage of systolic readings greater than 140 mm Hg and diastolic readings greater than 90 mm Hg) were obtained and interpreted. Mean awake systolic and diastolic pressures ranged from 125 +/- 10 to 137 +/- 17 mm Hg and 70 +/- 8 to 71 +/- 9 mm Hg, respectively. The systolic and diastolic trends of subjects' blood pressures taken during office visits and the 24-hour measurements were similar. Ranges for systolic and diastolic blood pressure loads from youngest to oldest ages were 9% +/- 14% to 25% +/- 20% and 3% +/- 7% to 4% +/- 7%, respectively. A comparison of blood pressure means from our sample that were taken during office visits and blood pressure means from a 2122-patient community survey demonstrated that our sample was reflective of an unselected population.
A Study of Chemoprophylaxis of Postpartum Urinary-Tract Infection
Authors: Marvin Turck, Robert G. Petersdorf
Journal: JAMA (1962)

There is evidence that routine catheterization of the urethra at the time of delivery has contributed to the frequency of postpartum bacteriuria. The possibility of preventing bacteriuria under these conditions was studied in 415 healthy women who had normal spontaneous deliveries preceded by routine catheterization. Of these, a test group of 217 received antimicrobial (sulfamethoxypyridazine) therapy whereas a contratest group of 198 was treated with a placebo. Two patients in the test group and 17 in the contratest group developed symptomatic urinary-tract infection during the study. The effectiveness of the prophylaxis was clearly demonstrated. Bacteriuria appearinwhere-r delivery did not persist, whereas patients with evidence of infection at the time of delivery tended to have bacteria in the urine at the visit 6 weeks post partum.
Interleukin 21 Enhances Antibody-Mediated Tumor Rejection
Authors: Mark J. Smyth, Michele W.L. Teng, Janelle Sharkey, Jennifer A. Westwood, Nicole M. Haynes, Hideo Yagita, Kazuyoshi Takeda, Pallavur V. Sivakumar, Michael H. Kershaw
Journal: Cancer Research (2008)

Abstract Interleukin-21 (IL-21) is a cytokine with structural and sequence homology to IL-2 and IL-15 that has antitumor activity alone in mouse experimental tumor models and a tolerable safety profile in phase I trials in patients with metastatic melanoma and renal cell carcinoma. Several monoclonal antibodies (mAb) targeted at tumor-associated antigens also have improved antitumor activities in mice when used in combination with IL-21. Recently, we described a rational three antibody-based approach (triple mAb, TrimAb) to eradicating established mouse tumors that required the generation of tumor-reactive CD8+ T cells and IFN-γ. Herein, we show that sequentially combining TrimAb with recombinant IL-21 can significantly improve the antitumor activity of this combination against very advanced disease. These data further support the use of IL-21 in adjuvant settings where strong T cell–mediated immune responses to tumors can be generated. [Cancer Res 2008;68(8):3019–25]
Education and Training in Preventive Medicine and Public Health
Authors: Alexander D. Langmuir
Journal: New England Journal of Medicine (1964)

THERE is general agreement that the basic science underlying preventive medicine and public health is epidemiology, but there is little agreement on what epidemiology is. To some it is still the narrow archaic view, the science of doctrine of epidemics. To others it is the all-embracing concept, the natural history of disease. Neither of these adequately identifies the emerging character of this important field of medicine and public health.There is need to search for some common ground of agreement on the methods, functions and scope of epidemiology. Only when this is found can the science be taught . . .
Differential distribution of the Sodium-vitamin C cotransporter-1 along the proximal tubule of the mouse and human kidney
Authors: Tamara Castro, Marcela Low, Katterine Salazar, Hernán Montecinos, Manuel Cifuentes, Alejandro J. Yáñez, Juan Carlos Slebe, Carlos D. Figueroa, Karin Reinicke, María de los Angeles García, Juan Pablo Henriquez, Francisco Nualart
Journal: Kidney International (2008)
Are religion and religiosity important to end-of-life decisions and patient autonomy in the ICU? The Ethicatt study
Authors: Hans-Henrik Bülow, Charles L. Sprung, Mario Baras, Sara Carmel, Mia Svantesson, Julie Benbenishty, Paulo A. Maia, Albertus Beishuizen, Simon Cohen, Daniel Nalos
Journal: Intensive Care Medicine (2012)
SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis
Authors: Lin Yu, Xin Liu, Kang Cui, Yanbo Di, Lingbiao Xin, Xiaoming Sun, Wei Zhang, Xi Yang, Minxin Wei, Zhi Yao, Jie Yang
Journal: Cancer Research (2015)

Abstract SND1 is an AEG-1/MTDH/LYRIC-binding protein that is upregulated in numerous human cancers, where it has been assigned multiple functional roles. In this study, we report its association with the TGFβ1 signaling pathway, which promotes epithelial–mesenchymal transition (EMT) in breast cancer. SND1 was upregulated in breast cancer tissues, in particular in primary invasive ductal carcinomas. Transcriptional activation of the SND1 gene was controlled by the TGFβ1/Smad pathway, specifically by activation of the Smad2/Smad3 complex. The SND1 promoter region contained several Smad-specific recognition domains (RD motifs), which were recognized and bound by the Smad complex that enhanced the transcriptional activation of SND1. We found that SND1 promoted expression of the E3 ubiquitin ligase Smurf1, leading to RhoA ubiquitination and degradation. RhoA degradation in breast cancer cells disrupted F-actin cytoskeletal organization, reduced cell adhesion, increased cell migration and invasion, and promoted metastasis. Overall, our results define a novel role for SND1 in regulating breast tumorigenesis and metastasis. Cancer Res; 75(7); 1275–86. ©2015 AACR.
Plasma Free Fatty Acid Concentrations in Obesity
Authors: Lionel H. Opie, Paul G. Walfish
Journal: New England Journal of Medicine (1963)

ADIPOSE tissue, previously thought to be metabolically inert, has now been recognized as one of the most active tissues in the body,1 being a major site of insulin activity and carbohydrate-lipid interaction. As a result, there has been a renewed interest in the problems of obesity, with a re-examination of lipid metabolism for possible differences between obese and normal subjects. The purpose of the present study is to analyze one parameter of lipid metabolism in obesity — namely, the concentration of plasma free fatty acid (FFA = nonesterified fatty acid = NEFA).The primary source from which lipid is mobilized . . .
Delivery of FGF Genes to Wound Repair Cells Enhances Arteriogenesis and Myogenesis in Skeletal Muscle
Authors: John Doukas, Kate Blease, Darren Craig, Chenglie Ma, Lois A. Chandler, Barbara A. Sosnowski, Glenn F. Pierce
Journal: Molecular Therapy (2002)

Tissue repair is driven by migratory macrophages and fibroblasts that infiltrate injury sites and secrete growth factors. We now report the enhancement of skeletal muscle repair by targeting transgene delivery to these repair cells using matrix-immobilized gene vectors. Plasmid and adenovirus vectors immobilized in collagen–gelatin admixtures were delivered to excisional muscle wounds, and when encoding either fibroblast growth factor-2 (FGF2) or FGF6 transgenes, produced early angiogenic responses that subsequently remodeled into arteriogenesis. FGF2 gene delivery enhanced the number of CD31+ endothelial cells present at treatment sites > 6-fold by day 14, and muscular arteriole density up to 11-fold by day 21 (P<0.0001). Muscle repair was also enhanced, as FGF gene–treated wounds filled with regenerating myotubes expressing the marker CD56 (an average 20-fold increase in CD56 expression versus controls, P<0.0001). These responses required transfection of a threshold level of repair cells, achievable only in injured muscles, and were transgene-driven, as neither platelet-derived growth factor-B (PDGFB) gene nor FGF2 protein delivery produced equivalent responses. In conclusion, using biomatrices to direct gene delivery to repair cells allows for relatively complex regenerative processes such as arteriogenesis and myogenesis, and therefore represents a promising approach to treating injured and ischemic muscle. Tissue repair is driven by migratory macrophages and fibroblasts that infiltrate injury sites and secrete growth factors. We now report the enhancement of skeletal muscle repair by targeting transgene delivery to these repair cells using matrix-immobilized gene vectors. Plasmid and adenovirus vectors immobilized in collagen–gelatin admixtures were delivered to excisional muscle wounds, and when encoding either fibroblast growth factor-2 (FGF2) or FGF6 transgenes, produced early angiogenic responses that subsequently remodeled into arteriogenesis. FGF2 gene delivery enhanced the number of CD31+ endothelial cells present at treatment sites > 6-fold by day 14, and muscular arteriole density up to 11-fold by day 21 (P<0.0001). Muscle repair was also enhanced, as FGF gene–treated wounds filled with regenerating myotubes expressing the marker CD56 (an average 20-fold increase in CD56 expression versus controls, P<0.0001). These responses required transfection of a threshold level of repair cells, achievable only in injured muscles, and were transgene-driven, as neither platelet-derived growth factor-B (PDGFB) gene nor FGF2 protein delivery produced equivalent responses. In conclusion, using biomatrices to direct gene delivery to repair cells allows for relatively complex regenerative processes such as arteriogenesis and myogenesis, and therefore represents a promising approach to treating injured and ischemic muscle.
T Helper Cell Type 2 Cytokine–Mediated Comitogenic Responses and Ccr3 Expression during Differentiation of Human Mast Cells in Vitro
Authors: Hiroshi Ochi, W. Mona Hirani, Qian Yuan, Daniel S. Friend, K. Frank Austen, Joshua A. Boyce
Journal: The Journal of Experimental Medicine (1999)

Mast cells (MCs) arise in situ from circulating stem cell factor (SCF)-dependent committed progenitors (PrMCs) and accumulate at sites of allergic mucosal inflammation. We hypothesized that human (h)PrMCs and their mature counterparts might share overlapping patterns of chemokine and cytokine receptor utilization with eosinophils, basophils, and T helper type 2 (Th2) lymphocytes for their homing and allergy-associated hyperplasia. We have characterized committed hPrMCs and fully mature hMCs derived in vitro from cord blood for their functional responses to chemokine and cytokine agonists germane to allergic inflammation and for their maturation-related expression of the corresponding receptors. After 4 wk of culture in the presence of recombinant stem cell factor (SCF), interleukin (IL)-6, and IL-10, the cells were characterized as hPrMCs based upon their uniform surface expression of c-kit and CD13, low-level expression of Fc∈RIα, absence of CD14 and CD16 expression, and immunoreactivity for MC chymase in &amp;gt;80%, and about half were immunoreactive for tryptase and metachromatic with toluidine blue. By week 9, the cells had matured into hMCs, identified by higher levels of c-kit, continued expression of CD13 and low-level Fc∈RIα, uniform toluidine blue metachromasia, and uniform immunoreactivity for both tryptase and chymase. The 4-wk-old hPrMCs expressed four chemokine receptors (CXCR2, CCR3, CXCR4, and CCR5). Each receptor mediated transient rapid calcium fluxes in response to its respective ligand. Both recombinant human eotaxin and stromal cell–derived factor 1α elicited chemotaxis of hPrMCs. Only CCR3 was retained on the mature 9-wk-old hMCs from among these chemokine receptors, and hMCs responded to eotaxin with a sustained calcium flux but without chemotaxis. The Th2 cytokines IL-3, IL-5, IL-6, IL-9, and granulocyte/macrophage colony-stimulating factor each augmented the SCF-dependent proliferation of hPrMCs and hMCs. In contrast, the prototypical Th1 cytokine, interferon γ, suppressed SCF-driven proliferation of both hPrMCs and hMCs. Thus, throughout their development in vitro, hMCs obey SCF-dependent, cytokine-driven mitogenic responses that reflect a Th2-type polarization characteristic of allergy and asthma. Furthermore, committed hPrMCs have a unique profile of chemokine receptor expression from among reported hematopoietic cells, including CCR3, which is shared with the other cells central to allergic inflammation (eosinophils, basophils, and Th2 lymphocytes).
Ethacrynic Acid in Blood Transfusion--its Effects on Plasma Volume and Urine Flow in Severe Anaemia in Pregnancy
Authors: K. A. Harrison
Journal: BMJ (1968)

Thirty grossly anaemic pregnant Nigerian women with venous haematocrit levels varying between 6 and 17%, had their plasma volumes estimated by the Evans blue dye dilution technique, both before and immediately after direct transfusion of packed blood cells. Parenteral ethacrynic acid was added to the blood for transfusion in 20 patients, seven of whom were in anaemic heart failure on admission. Ethacrynic acid used in this way was successful in the prevention of acute pulmonary oedema, and it produced acute diuresis as well as a reduction of plasma volume in the majority of cases. This technique of direct transfusion with ethacrynic acid is simple, and it may well replace exchange transfusion as a means of treating patients with anaemic heart failure.
Targeting B-cell anergy in chronic lymphocytic leukemia
Authors: Benedetta Apollonio, Cristina Scielzo, Maria Teresa Sabrina Bertilaccio, Elisa ten Hacken, Lydia Scarfò, Pamela Ranghetti, Freda Stevenson, Graham Packham, Paolo Ghia, Marta Muzio, Federico Caligaris-Cappio
Journal: Blood (2013)