tbuckley/cabot-search huggingface dataset:
The Complete Blood Count and Physician Payment
Authors: JAMES M. MOSS
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 April 1987The Complete Blood Count and Physician PaymentJAMES M. MOSS, M.D.JAMES M. MOSS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-106-4-642_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: As pointed out by Shapiro and Greenfield (1), a complete blood count and leukocyte differential count in an asymptomatic patient is usually normal, and when done as a routine procedure adds little to the diagnosis. The same can be said for routine urinalysis, automated blood chemistry profile, chest roentgenograms, and electrocardiograms. However, any physician can remember patients whose lives were saved because of an abnormality detected on one of these routine tests. All of us can recall patients in whom unsuspected anemia led to the diagnosis of gastrointestinal malignancy; an abnormal urinalysis that led to the diagnosis...References1. SHAPIROGREENFIELD MS. The complete blood count and leucocyte differential count: an approach to their rational application. Ann Intern Med. 1987;106:65-74. LinkGoogle Scholar2. . Medicare payment for physician services. Ann Intern Med. 1987;106:151-63. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 1707 Osage Street; Alexandria, VA 22302 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1987Volume 106, Issue 4Page: 642-642KeywordsAnemiaBlood chemistryComplete blood countElectrocardiographyThorax Issue Published: 1 April 1987 PDF downloadLoading ...
Abstract 5256: The identification of fatty acid synthase (FASN) as a candidate oncogene and therapeutic target in neuroblastoma
Authors: Patrick A. Mayes, Sharon Diskin, Edward F. Attiyeh, Yana Toporovskaya, John M. Maris
Journal: Cancer Research (2010)

Abstract Neuroblastoma is a common and lethal pediatric cancer. More than half of patients are at high-risk for relapse and die despite intensive therapy; thus presenting an urgent need for new, rationally designed drugs. To address the need for new therapeutic targets we sought to identify metabolic genes that are critical to neuroblastoma growth and survival. We restricted our analysis to a set of 12 metabolic genes that can be targeted therapeutically and had previously been implicated in other cancers. Analysis of 188 primary human neuroblastomas genotyped on the Illumina HumanHap SNP Array identified high-level, unbalanced gain at the FASN locus (17q25) in 23% of tumors. Analysis of FASN mRNA expression in 99 of these primary neuroblastomas using the IlluminaHT Expression Array identified significant increases in FASN expression restricted to high-risk neuroblastomas with amplification of the MYCN oncogene (P=0.0001). Within the subset of high-risk tumors with MYCN amplification, those that harbored FASN DNA copy number gains showed greater FASN mRNA expression than those with two copy FASN DNA. We next tested siRNAs targeted to the set of 12 metabolic genes in a panel of 12 neuroblastoma cell lines. We found that siRNA inhibition of fatty acid synthase (FASN) and hexokinase 2 (HK2) resulted in significant growth inhibition in 9/12 and 6/12 cell lines, respectively, whereas the others showed no appreciable cytotoxicity. Inhibition of FASN resulted in significant growth inhibition and apoptosis in 8/8 neuroblastoma cell lines with MYCN amplification, suggesting a synthetic lethal effect of FASN inhibition in neuroblastomas with MYCN amplification. Taken together, an integrated genomic and functional analytic approach has identified fatty acid synthase, a key enzymatic mediator of de novo fatty acid metabolism, as a candidate oncogene and therapeutic target in neuroblastoma, especially those harboring MYCN amplification. Ongoing analyses of pharmacologic inhibitors of FASN in neuroblastoma cell line animal models, including impact on global lipidomic profiles will be reported. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5256.
The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes: II. Nature of the responding cells.
Authors: A S Kong, S I Morse
Journal: The Journal of Experimental Medicine (1977)

The mitogenic response of murine lymphocytes to the lymphocytosis-promoting factor of Bordetella pertussis has been shown to be due to activation of T cells. The selectivity of responsiveness to LPF with respect to the population of T cells which is stimllated, differs from that of PHA as well as Con A, and the surface receptors are different. A population of adherent cells, which does not appear to consist of macrophages or other phagocytic cells, is required for the T-cell response.
Cytogenetic Technology — Genotype and Phenotype
Authors: David H. Ledbetter
Journal: New England Journal of Medicine (2008)

In this issue of the Journal, Mefford et al.1 describe an association between a microdeletion at 1q21.1 and a diverse range of impairments: mental retardation associated with microcephaly, cardiac abnormalities, or cataracts. A microdeletion at 16p11.2, causing autism or mental retardation, was reported earlier this year in the Journal.2 These discoveries were made possible by a technologic revolution in human cytogenetics: genomewide assessment of copy-number alterations (deletions and duplications) by means of high-density array technologies, hereafter referred to as cytogenetic arrays.35 The resultant proliferation of new cytogenetic syndromes is reminiscent of an earlier era in human cytogenetics: "During . . .
Effects of Early Onset Asthma and <i>In Utero</i> Exposure to Maternal Smoking on Childhood Lung Function
Authors: Frank D. Gilliland, Kiros Berhane, Yu-Fen Li, Edward B. Rappaport, John M. Peters
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Both in utero exposures to maternal smoking and asthma are associated with chronic deficits in lung function. We hypothesized that in utero exposure affects lung function in children without asthma and synergistically affects children with early onset asthma. To investigate effects of in utero exposure and age at asthma diagnosis on lung function, we examined longitudinal medical history, tobacco smoke exposure, and lung function data from 5,933 participants in the Children's Health Study. We found that children exposed in utero, but without asthma, showed decreased FEV1/FVC, FEF25-75, and FEF25-75/FVC ratio. Among children without in utero exposure, early asthma diagnosis was associated with larger decreases in FEV1, FEF25-75, and FEV1/FVC ratio compared with later diagnosed asthma. Children with in utero exposure alone and early onset asthma showed deficits in FEV1 (-13.6%; 95% confidence interval [CI], -18.9 to -8.2) and FEF25-75 (-29.7%; 95% CI, -37.8 to -20.5) among boys; and FEF25-75 (-26.6%; 95% CI, -36.4 to -15.1) and FEV1/FVC (-9.3%; 95% CI, -12.9 to -5.4) among girls. The absolute differences in FEF25-75 associated with in utero exposure increased with age in children with early onset asthma. We found little evidence for effects from environmental tobacco smoke exposure alone. In summary, deficits in lung function were largest among children with in utero exposure and early onset asthma.
GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice.
Authors: M R Stämpfli, R E Wiley, G S Neigh, B U Gajewska, X F Lei, D P Snider, Z Xing, M Jordana
Journal: Journal of Clinical Investigation (1998)

The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF can initiate a Th2-driven, eosinophilic inflammation in the airways. On day -1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF). From day 0 to day 9 mice were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen.
P2-212: Final analysis of a phase II trial of concomitant docetaxel/radiation followed by consolidation docetaxel/cisplatin in unresectable stage IIIa and IIIb non small cell lung cancer- TAX-AU-6022 study
Authors: Nimit Singhal, Michael P. Brown, Sudarshan S. Nayagam, Martin Borg, Ian N. Olver
Journal: Journal of Thoracic Oncology (2007)
Health secretary defends decision to restrict entry of overseas medical graduates
Authors: Lynn Eaton
Journal: BMJ (2008)

Health secretary Alan Johnson defended his department’s decision to try to restrict the number of medical graduates entering the United Kingdom from outside the European Economic Area (EEA) during his evidence on Monday afternoon to the parliamentary health select committee.

Kevin Barron, chairman of the committee, which is investigating the government’s Modernising Medical Careers (MMC) policy, asked whether the minister felt a moral obligation towards those overseas doctors who had helped to support the NHS for so long.

“No one could suggest in any way that this is failing to meet some moral obligation. This is the right way to go,” Mr Johnson said. “The contribution international medical graduates have made has been enormous.

“You are quite right we would not have been able to run the health service without their contribution. But we have drained the world of medical graduates. I don’t think …
Meaningful Disparities Reduction Through Research and Translation Programs
Authors: Marshall H. Chin, Don Goldmann
Journal: JAMA (2011)

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 P5-08-01: Systematic interrogation of resistance to HER2-directed therapy identifies a survival pathway activated by PRKACA and PIM1
Authors: SE Moody, AC Schinzel, S Singh, F Izzo, MR Strickland, LY Luo, SR Thomas, JS Boehm, SY Kim, ZC Wang, WC Hahn
Journal: Cancer Research (2013)

Abstract Amplification and/or overexpression of the receptor tyrosine kinase HER2 occurs in 20-25% of breast cancers, and is associated with poor prognosis. Targeting of HER2 with drugs such as trastuzumab, lapatinib, or pertuzumab has led to clinical benefit in patients with both metastatic and early-stage HER2-amplified breast cancer. However, resistance and disease progression always occurs in patients with metastatic disease, and many patients with early-stage breast cancer experience recurrences despite adjuvant anti-HER2 therapy. As such, understanding the mechanisms of resistance to anti-HER2 therapy has important clinical implications. Recent studies have identified mutations in PIK3CA, the gene encoding the catalytic subunit of Phosphatidylinositol 3 kinase (PI3K), as one mechanism of resistance to trastuzumab. However, such mutations are present in only a fraction of trastuzumab-resistant breast cancers. We therefore sought to uncover novel mechanisms of resistance to anti-HER2 therapy through an unbiased screen for kinases and kinase-related molecules that are able to rescue HER2-amplified breast cancer cells from HER2 inhibition. We utilized a library of nearly 600 lentivirally-delivered open reading frames (ORFs) to constitutively express the coding sequence of each molecule individually in HER2-amplified BT474 breast cancer cells in arrayed high-throughput format. We conducted two parallel screens for the ability of each of these molecules to rescue cells from anti-HER2 therapy: one in which we treated the cells with a lapatinib-like drug that inhibits the kinase activity of HER2 and EGFR, and one in which we lentivirally delivered a short hairpin RNA that suppresses expression of HER2. We identified those ORFs that restored viability of BT474 cells to greater than two standard deviations above the median of all ORFs in each screen. Multiple members of the MAPK and PI3K signaling pathways scored in both screens, serving to validate the approach. In addition, the survival kinases PIM1 and PRKACA scored robustly. Mechanistic studies suggest that these kinases may confer resistance by restoring the phosphorylation of, and thereby inactivating, the pro-apoptotic protein BAD. Consistent with this finding, overexpression of Bcl-xl, which is inhibited by BAD, also conferred resistance to lapatinib in HER2-amplified breast cancer cells. Furthermore, pharmacological blockade of Bcl-xl and Bcl-2 with ABT-263 enhanced lapatinib-induced killing of HER2-amplified breast cancer cells in vitro, and partially abrogated the rescue conferred by both PRKACA and PIM1. These findings suggest that combined inhibition of HER2 and the anti-apoptotic molecules Bcl-xl and Bcl-2 could enhance tumor cell eradication and prevent or delay the emergence of resistant disease. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-01.
Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides
Authors: Richard S. Geary, Daniel Norris, Rosie Yu, C. Frank Bennett
Journal: Advanced Drug Delivery Reviews (2015)

Pharmacokinetic properties of oligonucleotides are largely driven by chemistry of the backbone and thus are sequence independent within a chemical class. Tissue bioavailability (% of administered dose) is assisted by plasma protein binding that limits glomerular filtration and ultimate urinary excretion of oligonucleotides. The substitution of one non-bridging oxygen with the more hydrophobic sulfur atom (phosphorothioate) increases both plasma stability and plasma protein binding and thus, ultimately, tissue bioavailability. Additional modifications of the sugar at the 2' position, increase RNA binding affinity and significantly increase potency, tissue half-life and prolong RNA inhibitory activity. Oligonucleotides modified in this manner consistently exhibit the highest tissue bioavailability (>90%). Systemic biodistribution is broad, and organs typically with highest concentrations are liver and kidney followed by bone marrow, adipocytes, and lymph nodes. Cell uptake is predominantly mediated by endocytosis. Both size and charge for most oligonucleotides prevents distribution across the blood brain barrier. However, modified single-strand oligonucleotides administered by intrathecal injection into the CSF distribute broadly in the CNS. The majority of intracellular oligonucleotide distribution following systemic or local administration occurs rapidly in just a few hours following administration and is facilitated by rapid endocytotic uptake mechanisms. Further understanding of the intracellular trafficking of oligonucleotides may provide further enhancements in design and ultimate potency of antisense oligonucleotides in the future.
Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis.
Authors: L B Klickstein, C Shapleigh, E J Goetzl
Journal: Journal of Clinical Investigation (1980)

The predominant lipoxygenase products of arachidonic acid were extracted and purified from synovial fluid and sonicates of synovial tissue of patients with rheumatoid arthritis (RA), spondyloarthritis (SA), or a noninflammatory arthropathy (NIA). The concentration of 5(S),12(R)-dihydroxy-6,8,10-(trans/trans/cis)-14-cis-eicosatetraenoic acid (leukotriene B4) in synovial fluid was elevated significantly in patients with RA and a positive latex test for rheumatoid factor (P < 0.05, n = 14) and in patients with SA (P < 0.05, n = 10), compared with that of subjects with NIA (n = 9). The content of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), but not of leukotriene B4, was elevated significantly in synovial tissue of seven patients with RA in comparison with that of four subjects with NIA (P < 0.05). A single intra-articular injection of corticosteroid significantly lowered the synovial fluid level of leukotriene B4 in six patients with RA. These data suggest an involvement of the potent chemotactic factors 5-HETE and leukotriene B4 in human inflammatory disease.
Studies in Serum Lipids
Authors: J. B. CROMIE, K. J. THOMSON, O. S. CULLIMORE, E. F. BEACH
Journal: Circulation (1963)

Repeated measurements of the fasting and 2-hour postprandial serum lipids (cholesterol, phospholipid, and triglyceride) of "normal" [see table in the PDF file] subjects and subjects with atherosclerotic heart disease when consuming diets of high-, low-, or "normal"-fat content have been made. Triglyceride levels correlated better with the clinical diagnosis of heart disease than did cholesterol or phospholipid levels. The wide fluctuations in triglyceride levels in the same [see table in the PDF file] subject (normal or atherosclerotic) when on a "normal self-selected" diet and the unexpected findings when a short-term (3-day) period of dietary fat manipulation render the value of random triglyceride levels as an indictator of the presence or likely development of atherosclerotic heart disease of little or no value in the individual subject.
CXC-Chemokine Receptor 4 Antagonist AMD3100 Promotes Cardiac Functional Recovery After Ischemia/Reperfusion Injury via Endothelial Nitric Oxide Synthase–Dependent Mechanism
Authors: Kentaro Jujo, Masaaki Ii, Haruki Sekiguchi, Ekaterina Klyachko, Sol Misener, Toshikazu Tanaka, Jörn Tongers, Jérôme Roncalli, Marie-Ange Renault, Tina Thorne, Aiko Ito, Trevor Clarke, Christine Kamide, Yukio Tsurumi, Nobuhisa Hagiwara, Gangjian Qin, Michio Asahi, Douglas W. Losordo
Journal: Circulation (2012)

Background— CXC-chemokine receptor 4 (CXCR4) regulates the retention of stem/progenitor cells in the bone marrow (BM), and the CXCR4 antagonist AMD3100 improves recovery from coronary ligation injury by mobilizing stem/progenitor cells from the BM to the peripheral blood. Thus, we investigated whether AMD3100 also improves recovery from ischemia/reperfusion injury, which more closely mimics myocardial infarction in patients, because blood flow is only temporarily obstructed. Methods and Results— Mice were treated with single subcutaneous injections of AMD3100 (5 mg/kg) or saline after ischemia/reperfusion injury. Three days later, histological measurements of the ratio of infarct area to area at risk were smaller in AMD3100-treated mice than in mice administered saline, and echocardiographic measurements of left ventricular function were greater in the AMD3100-treated mice at week 4. CXCR4 + cells were mobilized for just 1 day in both groups, but the mobilization of sca1 + /flk1 + cells endured for 7 days in AMD3100-treated mice compared with just 1 day in the saline-treated mice. AMD3100 upregulated BM levels of endothelial nitric oxide synthase (eNOS) and 2 targets of eNOS signaling, matrix metalloproteinase-9 and soluble Kit ligand. Furthermore, the loss of BM eNOS expression abolished the benefit of AMD3100 on sca1 + /flk1 + cell mobilization without altering the mobilization of CXCR4 + cells, and the cardioprotective effects of AMD3100 were retained in eNOS-knockout mice that had been transplanted with BM from wild-type mice but not in wild-type mice with eNOS-knockout BM. Conclusions— AMD3100 prolongs BM progenitor mobilization and improves recovery from ischemia/reperfusion injury, and these benefits appear to occur through a previously unidentified link between AMD3100 and BM eNOS expression.
Slowly Sedimenting Mercaptoethanol-resistant Antinuclear Factors Related Antigenically to M Immunoglobulins (γ1M-Globulin) in Patients with Systemic Lupus Erythematosus *
Authors: Naomi F. Rothfield, Blas Frangione, Edward C. Franklin
Journal: Journal of Clinical Investigation (1965)

The human immunoglobulins currently recog- nized can be divided into three major classes: the 7 S y2-globulins (G immunoglobulins, IgG); the ylM-globulins (M immunoglobulins, IgM); and the 'ylA-globulins (A immunoglobulins, IgA) 1 (2).These proteins can be readily distinguished from each other with specific antisera directed against the antigenic determinants associated with the heavy chains characteristic of each class.In addition, M immunoglobulins have a sedimentation coefficient of 19 S (mol wt of about 1,000,000), and their antibody activity is destroyed by treat- ment with 2-mercaptoethanol or other thiol com- pounds, whereas G immunoglobulins have a sedi- mentation coefficient of 7 S (mol wt of about 160,-000), and their antibody activity is not significantly affected by treatment with thiol compounds.Most A immunoglobulins sediment with the IgG