tbuckley/cabot-search huggingface dataset:
Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response
Authors: Wolfgang W.A. Schamel, Ignacio Arechaga, Ruth M. Risueño, Hisse M. van Santen, Pilar Cabezas, Cristina Risco, José M. Valpuesta, Balbino Alarcón
Journal: The Journal of Experimental Medicine (2005)

A long-standing paradox in the study of T cell antigen recognition is that of the high specificity–low affinity T cell receptor (TCR)–major histocompatibility complex peptide (MHCp) interaction. The existence of multivalent TCRs could resolve this paradox because they can simultaneously improve the avidity observed for monovalent interactions and allow for cooperative effects. We have studied the stoichiometry of the TCR by Blue Native–polyacrylamide gel electrophoresis and found that the TCR exists as a mixture of monovalent (αβγεδεζζ) and multivalent complexes with two or more ligand-binding TCRα/β subunits. The coexistence of monovalent and multivalent complexes was confirmed by electron microscopy after label fracture of intact T cells, thus ruling out any possible artifact caused by detergent solubilization. We found that although only the multivalent complexes become phosphorylated at low antigen doses, both multivalent and monovalent TCRs are phosphorylated at higher doses. Thus, the multivalent TCRs could be responsible for sensing low concentrations of antigen, whereas the monovalent TCRs could be responsible for dose-response effects at high concentrations, conditions in which the multivalent TCRs are saturated. Thus, besides resolving TCR stoichiometry, these data can explain how T cells respond to a wide range of MHCp concentrations while maintaining high sensitivity.
Healing of Empyema Cavities
Authors: P. R. Allison
Journal: BMJ (1938)

{~~~~~~~~~~~~~~~N E D I C A L J O U ' R N ' A I , (1937) gave daily doses of ergotamine tartrate, which they found diminished suicidal, homicidal, and destructive activity (Linderman observed the converse with adrenaline injections-namely, that patients became more subjective and introspective).Such treatments offer great individual and economic hopefulness, provided sufficient further scientific study of their relation to cerebral capillary function is made to render them scientific instead of empirical: in this direction the work of the Harvard Medical School, Boston, is to be highly commended.
Necrosis of skin induced by coumarin in a patient deficient in protein S.
Authors: V. Grimaudo, F. Gueissaz, J. Hauert, A. Sarraj, E. K. Kruithof, F. Bachmann
Journal: BMJ (1989)

weeks plasma total thyroxine and thyroid stimulating hormone concentrations were normal.He had no diarrhoea or allergic symptoms and was more active and lively.Iodine supplements were stopped.After eight weeks his response to thyrotrophin releasing hormone was normal.He had gained 1 5 kg in weight and 2 0 cm in height.1
Relationship between myocardial oxygen consumption, coronary flow, and adenosine release in an improved isolated working heart preparation of guinea pigs.
Authors: H Bardenheuer, J Schrader
Journal: Circulation Research (1983)

We describe herein an isolated working heart preparation of guinea pigs, in which coronary perfusion pressure can be varied independently from afterload by directing left ventricular stroke volume into an artificial circulation. This preparation proved to be functionally stable, exhibited hemodynamic features characteristic of the heart in situ, and shows the phenomena of flow autoregulation, reactive hyperemia, and hypoxic and metabolic vasodilation. Myocardial oxygen consumption and coronary flow were tightly coupled when cardiac work was enhanced by either 1.5-6.0 X 10(-9) M isoproterenol (r = 0.975) or changes of afterload (20-100 mm Hg) (r = 0.890). Isoproterenol-induced changes in adenosine release correlated with changes of coronary flow (r = 0.869) and myocardial oxygen consumption (r = 0.894). The concentrations of endogenously formed adenosine were within the vasodilatory range of exogenously applied adenosine. In contrast, afterload-induced changes in myocardial oxygen consumption were not associated with an enhanced release of adenosine, inosine, and hypoxanthine, and did not correlate with coronary resistance (r = 0.422). The specific activity in the effluent perfusate of intracoronarily infused [8-14C]adenosine was increased with elevated afterload, suggesting that less adenosine was liberated by the heart. Our findings indicate that adenosine formed in response to beta-adrenergic stimulation is a major metabolite adjusting coronary flow to myocardial needs. Adenosine, however, does not appear to be involved in the afterload-induced changes in coronary flow when coronary perfusion pressure and, thus, oxygen supply are increased simultaneously. It is likely that formation of adenosine is not triggered by changes in MVO2 as such, but may critically depend on the oxygen supply: demand ratio.
Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children
Authors: Brenda Eskenazi, Amy R. Marks, Asa Bradman, Kim Harley, Dana B. Barr, Caroline Johnson, Norma Morga, Nicholas P. Jewell
Journal: Environmental Health Perspectives (2007)

Organophosphate (OP) pesticides are widely used in agriculture and homes. Animal studies suggest that even moderate doses are neurodevelopmental toxicants, but there are few studies in humans.We investigated the relationship of prenatal and child OP urinary metabolite levels with children's neurodevelopment.Participating children were from a longitudinal birth cohort of primarily Latino farm-worker families in California. We measured six nonspecific dialkylphosphate (DAP) metabolites in maternal and child urine as well as metabolites specific to malathion (MDA) and chlorpyrifos (TCPy) in maternal urine. We examined their association with children's performance at 6 (n = 396), 12 (n = 395), and 24 (n = 372) months of age on the Bayley Scales of Infant Development [Mental Development (MDI) and Psychomotor Development (PDI) Indices] and mother's report on the Child Behavior Checklist (CBCL) (n = 356).Generally, pregnancy DAP levels were negatively associated with MDI, but child measures were positively associated. At 24 months of age, these associations reached statistical significance [per 10-fold increase in prenatal DAPs: beta = -3.5 points; 95% confidence interval (CI), -6.6 to -0.5; child DAPs: beta = 2.4 points; 95% CI, 0.5 to 4.2]. Neither prenatal nor child DAPs were associated with PDI or CBCL attention problems, but both prenatal and postnatal DAPs were associated with risk of pervasive developmental disorder [per 10-fold increase in prenatal DAPs: odds ratio (OR) = 2.3, p = 0.05; child DAPs OR = 1.7, p = 0.04]. MDA and TCPy were not associated with any outcome.We report adverse associations of prenatal DAPs with mental development and pervasive developmental problems at 24 months of age. Results should be interpreted with caution given the observed positive relationship with postnatal DAPs.
Murine CD14 gene expression in vivo: extramyeloid synthesis and regulation by lipopolysaccharide.
Authors: C Fearns, V V Kravchenko, R J Ulevitch, D J Loskutoff
Journal: The Journal of Experimental Medicine (1995)

A murine model system was used to study the distribution and regulation of CD14 gene expression in vivo. Western blot analysis failed to detect CD14 in plasma from untreated CB6 (BALB/c x C57Bl6) mice, but showed markedly increased levels of CD14 in plasma from mice treated with lipopolysaccharide (LPS). Plasma levels of CD14 increased in a time- and dose-dependent manner, reaching a maximum between 8 and 16 h. Northern blot analysis of total RNA extracted from mouse tissues revealed low, but significant, levels of CD14 mRNA in many tissues of untreated animals with the highest levels in uterus, adipose tissue, and lung. After intraperitoneal injection of LPS, induction of CD14 gene expression was detected in all organs examined with the extent of induction varying between organs. Induction of CD14 mRNA was both time and dose dependent. Maximum induction in the heart and lung was observed 2-4 h after injection of LPS, while liver and kidney showed maximal induction between 8 and 16 h. In situ hybridization showed that CD14 mRNA was expressed in myeloid cells in many tissues, and that expression in these cells was upregulated by LPS. Unexpectedly, CD14 mRNA was also detected in other cells within tissues, including epithelial cells, and expression in these cell types also was upregulated by LPS. Immunochemical analysis revealed that CD14 antigen colocalized to the cytoplasm of cells expressing CD14 mRNA. These studies demonstrate that CD14 gene expression is not restricted to myeloid cells, and that the level of expression of CD14 is influenced by exposure to LPS.
Patient-Centered Medical Home Intervention at an Internal Medicine Resident Safety-Net Clinic
Authors: Michael E. Hochman, Steven Asch, Arek Jibilian, Bharat Chaudry, Ron Ben-Ari, Eric Hsieh, Margaret Berumen, Shahrod Mokhtari, Mohamad Raad, Elisabeth Hicks, Crystal Sanford, Norma Aguirre, Chi-hong Tseng, Sitaram Vangala, Carol M. Mangione, David A. Goldstein
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3> The patient-centered medical home (PCMH) model holds promise for improving primary care delivery, but it has not been adequately tested in teaching settings. <h3>Design, Setting, and Participants</h3> We implemented an intervention guided by PCMH principles at a safety-net teaching clinic with resident physician providers. Two similar clinics served as controls. <h3>Main Outcomes and Measures</h3> Using a cross-sectional design, we measured the effect on patient and resident satisfaction using the Consumer Assessment of Healthcare Providers and Systems survey and a validated teaching clinic survey, respectively. Both surveys were conducted at baseline and 1 year after the intervention. We also measured the effect on emergency department and hospital utilization. <h3>Results</h3> Following implementation of our intervention, the clinic's score on the National Committee for Quality Assurance's PCMH certification tool improved from 35 to 53 of 100 possible points, although our clinic did not achieve all must-pass elements to qualify as a PCMH. During the 1-year study period, 4676 patients were exposed to the intervention; 39.9% of these used at least 1 program component. Compared with baseline, patient-reported access and overall satisfaction improved to a greater extent in the intervention clinic, and the composite satisfaction rating increased from 48% to 65% in the intervention clinic vs from 50% to 59% in the control sites (<i>P</i> = .04). The improvements were particularly notable for questions relating to access. For example, satisfaction with urgent appointment scheduling increased from 12% to 53% in the intervention clinic vs from 14% to 18% in the control clinics (<i>P</i> &lt; .001). Resident satisfaction also improved in the intervention clinic: the composite satisfaction score increased from 39% to 51% in the intervention clinic vs a decrease from 46% to 42% in the control clinics (<i>P</i> = .01). Emergency department utilization did not differ significantly between the intervention and control clinics, and hospitalizations increased from 26 to 27 visits per 1000 patients per month in the intervention clinic vs a decrease from 28 to 25 in the control clinics (<i>P</i> = .02). <h3>Conclusions and Relevance</h3> Our PCMH-guided intervention, which represented a modest but substantive step toward the PCMH vision, had favorable effects on patient and resident satisfaction at a safety-net teaching clinic but did not reduce emergency department or hospital utilization in the first year. Our experience may provide lessons for other teaching clinics in safety-net settings hoping to implement PCMH-guided reforms.
Abstract A36: Treatment of established dermal murine B16F10 melanoma with an attenuated <i>Toxoplasma gondii</i> eliminates the treated tumor and stimulates systemic antitumor immunity.
Authors: Steven Fiering, Jason R. Baird, Katelyn Byrne, Patrick Lizotte, David Mullins, Mary Jo turk
Journal: Cancer Research (2013)

Abstract While the surgical removal of dermal melanoma cures that lesion, it does nothing to stimulate antitumor immunity that could potentially identify and eliminate occult metastatic disease. An immune based treatment that eliminates the primary dermal melanoma could also potentially generate systemic immunity that will protect against metastatic disease. We have utilized an attenuated strain of Toxoplasma gondii (cps) to break tumor-mediated immunosuppression, stimulate an antitumor immune response that eliminates the dermal tumor, and generate systemic antitumor immunity that leads to rejection of subsequent dermal or intravenous challenges with B16F10. T. gondii is an obligate intracellular eukaryotic parasite that infects virtually any mammalian species. The cps strain is a uracil auxotroph that can be grown in vitro but is unable to replicate in vivo. Despite its lack of infectivity, it enters cells and stimulates a strong T-cell mediated immune response characterized by long lasted CD8 effector cells. The presence of cps in the tumor microenvironment modifies the phenotype of tumor infiltrating leukocytes, and along with the expected anti-Toxoplasma immune response there is antigen-spreading so that tumor antigens are responded to and the immune system recognizes subsequent tumor challenges when there is no associated cps. The treatment requires CD8 and NK cells for efficacy but does not require CD4 cells. The treatment also requires that the host express IL-12 and Ifn-g. The treatment requires live cps for efficacy and is effective in mice that are latently infected with another strain of T. gondii, so it could function in the high percentage of humans with latent T. gondii infection and an established immune response against T. gondii. Citation Format: Steven Fiering, Jason R. Baird, Katelyn Byrne, Patrick Lizotte, David Mullins, Mary Jo turk. Treatment of established dermal murine B16F10 melanoma with an attenuated Toxoplasma gondii eliminates the treated tumor and stimulates systemic antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A36.
Acute Hepatitis, Interstitial Nephritis, and Eosinophilia
Authors: Manfred Hauben
Journal: Annals of Internal Medicine (1995)

Letters1 April 1995Acute Hepatitis, Interstitial Nephritis, and EosinophiliaManfred Hauben and Carl AdlerManfred HaubenPfizer, New York, NY 10017-5755. Jamaica Hospital, New York, NY 11418.Search for more papers by this author and Carl AdlerPfizer, New York, NY 10017-5755. Jamaica Hospital, New York, NY 11418.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-7-199504010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Saliba and Herbert [1] observed an increased incidence of oxacillin-associated hepatotoxicity in patients with human immunodeficiency virus (HIV infection); however, this study did not account for intergroup differences in variables relevant to causality assessment of adverse drug reactions, such as concomitant medications, coexisting pathologic abnormalities, and treatment indication. We also found that patients with HIV infection may be at increased risk for drug-induced hepatotoxicity [2-4].Table 1. Laboratory Values during Treatment with Vancomycin and Aztreonam* A 35-year-old female inpatient with HIV infection who previously had adverse reactions ...References1. Saliba B, Herbert PN. Oxacillin hepatoxicity in HIV-infected patients (Letter). Ann Intern Med. 1994; 120:1048. Google Scholar2. Ackerman Z, Levy M. Hypersensitivity reactions to drugs in acquired immune deficiency syndrome. Postgraduate Medical Journal. 1989; 63:55-6. Google Scholar3. Harb GE, Jacobsen MA. Immunodeficiency virus (HIV) infection. Does it increase susceptibility to adverse drug reactions. Drug Safety. 1993; 9:1-8. Google Scholar4. Harb G, Alldredge G, Coleman E, Jacobsen M. Pharmacoepidemiology of adverse drug reactions in hospitalized patients with human immunodeficiency virus (HIV) disease. J Acquir Immune Defic Syndr. 1993; 6:919-26. Google Scholar5. Stricker BH. Antimicrobial agents. In: Stricker, BH. Drug Induced Hepatic Injury. 2d ed. New York: Elsevier; 1992:194,213. Google Scholar Author, Article, and Disclosure InformationAffiliations: Pfizer, New York, NY 10017-5755. Jamaica Hospital, New York, NY 11418. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byKidney biopsy findings in vancomycin-induced acute kidney injury: a pooled analysisVancomycin-Induced Acute Granulomatous Interstitial Nephritis: Therapeutic OptionsBiopsy-Proved Acute Tubulointerstitial Nephritis and Toxic Epidermal Necrolysis Associated with VancomycinAntibiotic-Associated Hepatitis: Update from 1990Aztreonam/vancomycin 1 April 1995Volume 122, Issue 7Page: 555-556KeywordsAdverse reactionsAminotransferasesDrugsEosinophiliaHIV infectionsLaboratory testsNephritisPenicillinVancomycinVomiting Issue Published: 1 April 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Can States Pick Up the Health Reform Torch?
Authors: Sara Rosenbaum
Journal: New England Journal of Medicine (2010)

It is impossible to recall another time when a single incident — in this case, the off-cycle election of a U.S. senator — so thoroughly implicated the long-term direction of U.S. health policy. Washington is still taking the full measure of Senator Scott Brown's victory in Massachusetts, but among seasoned observers, the election's potential fallout for health reform was evident even before the first votes were cast.1 The political narrative of the Brown victory is the stuff of legend: the loss of a Senate seat held by an iconic figure who devoted his half-century political career to the very issue . . .
Toward More Accurate Ancestral Protein Genotype–Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees
Authors: Mathieu Groussin, Joanne K. Hobbs, Gergely J. Szöllősi, Simonetta Gribaldo, Vickery L. Arcus, Manolo Gouy
Journal: Molecular Biology and Evolution (2014)

The resurrection of ancestral proteins provides direct insight into how natural selection has shaped proteins found in nature. By tracing substitutions along a gene phylogeny, ancestral proteins can be reconstructed in silico and subsequently synthesized in vitro. This elegant strategy reveals the complex mechanisms responsible for the evolution of protein functions and structures. However, to date, all protein resurrection studies have used simplistic approaches for ancestral sequence reconstruction (ASR), including the assumption that a single sequence alignment alone is sufficient to accurately reconstruct the history of the gene family. The impact of such shortcuts on conclusions about ancestral functions has not been investigated. Here, we show with simulations that utilizing information on species history using a model that accounts for the duplication, horizontal transfer, and loss (DTL) of genes statistically increases ASR accuracy. This underscores the importance of the tree topology in the inference of putative ancestors. We validate our in silico predictions using in vitro resurrection of the LeuB enzyme for the ancestor of the Firmicutes, a major and ancient bacterial phylum. With this particular protein, our experimental results demonstrate that information on the species phylogeny results in a biochemically more realistic and kinetically more stable ancestral protein. Additional resurrection experiments with different proteins are necessary to statistically quantify the impact of using species tree-aware gene trees on ancestral protein phenotypes. Nonetheless, our results suggest the need for incorporating both sequence and DTL information in future studies of protein resurrections to accurately define the genotype–phenotype space in which proteins diversify.
IMPACT OF MULTIVESSEL DISEASE WITH AND WITHOUT A CONCURRENT CHRONIC TOTAL OCCLUSION ON SHORT AND LONG-TERM MORTALITY IN ST-ELEVATION MYOCARDIAL INFARCTION PATIENTS WITH AND WITHOUT CARDIOGENIC SHOCK
Authors: Loes P. Hoebers, Bimmer E. Claessen, Wouter J. Kikkert, Annemarie Engstrom, Marije M. Vis, Karel T. Koch, Jan Baan, Jan G. Tijssen, Robbert J. de Winter, Jan J. Piek, Jose P. Henriques
Journal: Journal of the American College of Cardiology (2011)
End of Life
Authors: Ernlé W. D. Young
Journal: JAMA (2006)

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
Ronald David Graham
Authors: A. Graham
Journal: BMJ (2003)

General practitioner Clarkston, Glasgow (b Glasgow 1948; q Glasgow 1973; DRCOG, MRCGP), d 27 April 2003.​2003.




Figure 1




Ronnie Graham had interests in childhood asthma, palliative care, and work as a police surgeon. In tandem with medicine, Ronnie was a considerable sportsman. He maintained a single-figure golfing handicap, but it was rugby that brought him a university blue, membership of the Scottish Universities squad, and a long playing career for Glasgow Accies. Over many years he coached youth teams in and around Glasgow. His most notable achievement was organising the Festivals of Youth Rugby in 1997 and 1999. He leaves a wife, Edith, and two sons.
A study of estrogen metabolic clearance rates and transfer factors
Authors: W. C. Hembree, C. W. Bardin, M. B. Lipsett
Journal: Journal of Clinical Investigation (1969)

We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E(2)) and estrone (E(1)) during 2-hr and 12-hr infusions. When estradiol-(3)H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-(3)H levels increased slowly throughout the infusion. When estrone-(3)H was infused, constancy of estrone-(3)H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios C(E1E2) and C(E2E1) continually changed and transfer factors could not be calculated. The apparent "MCR'S" calculated on the basis of the 2-hr studies expressed as liters/24 hr per m(2) +/-SD were: "MCR(E1)" (women) 980 +/-94, (men) 1170 +/-95; "MCR(E2)" (women) 615 +/-17, (men) 830 +/-30. The estradiol "MCR's" differed significantly between men and women. "MCR(E2)" was the same using either estradiol-(14)C or -(3)H and was unchanged by the infusion of 170 mug of estradiol daily. Postmenopausal women had estrogen "MCR's" in the same range as premenopausal women. Excess glucocorticoids increased the "MCR(E2)."