tbuckley/cabot-search huggingface dataset:
<i>In vitro</i> T‐cell responses to β‐lactam drugs in immediate and nonimmediate allergic reactions
Authors: I. Luque, L. Leyva, M. José Torres, M. Rosal, C. Mayorga, J. M. Segura, M. Blanca, C. Juárez
Journal: Allergy (2001)

Background: β‐Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin. Methods: Fifty patients with a well‐documented history of allergic reactions to β‐lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty‐eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects. Results: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%. Conclusions: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T‐cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.
No Place Like Home — Testing a New Model of Care Delivery
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2008)

Seeking ways to slow the growth of Medicare spending and to better coordinate the health care it finances, the federal government is preparing to test the concept of the “medical home” in the Medicare program. In response to a mandate in the Tax Relief and Health Care Act of 2006, the staff at the Centers for Medicare and Medicaid Services (CMS) is developing a demonstration program that will operate for 3 years in rural, urban, and underserved areas in up to eight states. Congress has directed the agency to use the program to “redesign the health care delivery system to . . .
The effect of anti-tumour necrosis factor treatment on the antibody response to influenza vaccination
Authors: L B S Gelinck, A E van der Bijl, W E P Beyer, L G Visser, T W J Huizinga, R A van Hogezand, G F Rimmelzwaan, F P Kroon
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> The effect of anti-tumour necrosis factor (TNF) therapy on the antibody responses to vaccines is the subject of ongoing debate. Therefore, we investigated the effect of the three currently available anti-TNF agents on influenza vaccination outcomes in a patient population with long-standing disease. <h3>Methods:</h3> In a prospective cohort study, we assessed the antibody response upon influenza vaccination in 112 patients with long-standing autoimmune disease treated with immunosuppressive medication either with anti-TNF (etanercept, adalimumab or infliximab; n = 64) or without anti-TNF (n = 48) and a control group of 18 healthy individuals. Antibody responses were determined by haemagglutination inhibition assay, before and 4 weeks after vaccination. <h3>Results:</h3> The proportion of individuals with a protective titre (⩾40) after vaccination was large (80–94%) and did not significantly differ between the three groups. Post-vaccination geometric mean antibody titres against influenza (A/H3N2 and B) were significantly lower in the 64 patients treated with anti-TNF compared with the 48 patients not receiving anti-TNF, and the healthy controls. <h3>Conclusions:</h3> The antibody response to influenza vaccination in patients treated with anti-TNF is only modestly impaired. The proportion of patients that achieves a protective titre is not significantly diminished by the use of TNF blocking therapies.
Intercurrent Death after Hodgkin Disease Therapy in Radiotherapy and Adjuvant MOPP Trials
Authors: Steven L. Hancock
Journal: Annals of Internal Medicine (1988)

Study Objective: To assess long-term differences in mortality associated with initial Hodgkin disease therapy. Design: Retrospective review of patients treated in prospectively randomized clinical trials. Patients: Three hundred twenty-six patients with pathologic stage I, II, or III, A or B Hodgkin disease treated between 1967 and 1980 with median follow-up exceeding 14 years. Interventions: Patients at the same stage of disease were randomized to receive radiation alone (167 patients) or radiation followed by 6 cycles of mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (159 patients) with additional therapy for progression or recurrence. Measurements and Main Results: No significant differences between treatment regimens for actuarial survival, intercurrent disease, or Hodgkin disease mortality were seen. Thirty-three patients who received radiation alone and 30 patients who received adjuvant chemotherapy died without evident Hodgkin disease. Death was caused by second neoplasms in 28 patients (relative risk, 2.35; 95% CI, 1.46 to 3.24). Six patients developed acute myelogenous leukemia or a myeloproliferative disorder after treatment including MOPP. Chemotherapy exposure varied among the 8 patients with lung cancers, 6 with gastrointestinal and 3 with other adenocarcinomas, 3 with sarcomas, 1 with diffuse large cell lymphoma, and 1 with melanoma. Acute myocardial infarction caused 9 of 17 cardiovascular disease deaths with 5 occurring in patients between the ages of 33 and 43. Nonetheless, the risk for acute myocardial infarction was not clearly increased (relative risk, 0.86; 95% CI, 0.42 to 1.57). Fifteen patients died from infection: 5, opportunistic; 5, asplenic sepsis; and 5, other pneumonias. Two patients died in accidents, and 1 died from radiation pneumonitis. Conclusions: Adjuvant MOPP chemotherapy improved freedom from relapse without significant survival benefit or impairment. Leukemogenesis was the only lethal complication associated with MOPP. Survivors of Hodgkin disease had an increased risk for death from a second neoplasm, but no apparent increased risk for death from acute myocardial infarction.
Triggering the succinate receptor GPR91 on dendritic cells enhances immunity
Authors: Tina Rubic, Günther Lametschwandtner, Sandra Jost, Sonja Hinteregger, Julia Kund, Nicole Carballido-Perrig, Christoph Schwärzler, Tobias Junt, Hans Voshol, Josef G Meingassner, Xiaohong Mao, Gudrun Werner, Antal Rot, José M Carballido
Journal: Nature Immunology (2008)
Identification of Epoxyeicosatrienoic Acids as Endothelium-Derived Hyperpolarizing Factors
Authors: William B. Campbell, Debebe Gebremedhin, Phillip F. Pratt, David R. Harder
Journal: Circulation Research (1996)

Abstract Endothelial cells release several compounds, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF), that mediate the vascular effects of vasoactive hormones. The identity of EDHF remains unknown. Since arachidonic acid causes endothelium-dependent relaxations of coronary arteries through its metabolism to epoxyeicosatrienoic acids (EETs) by cytochrome P 450 , we wondered if the EETs represent EDHFs. Precontracted bovine coronary arteries relaxed in an endothelium-dependent manner to methacholine. The cytochrome P 450 inhibitors, SKF 525A and miconazole, significantly attenuated these relaxations. They were also inhibited by tetraethylammonium (TEA), an inhibitor of Ca 2+ -activated K + channels, and by high [K + ] o (20 mmol/L). Methacholine also caused hyperpolarization of coronary smooth muscle (−27±3.9 versus −40±5.1 mV), which was completely blocked by SKF 525A and miconazole. In vessels prelabeled with [ 3 H]arachidonic acid, methacholine stimulated the release of 6-ketoprostaglandin F 1α , 12-HETE, and the EETs. Arachidonic acid relaxed precontracted coronary arteries, which were also blocked by TEA, charybdotoxin, another Ca 2+ -activated K + channel inhibitor, and high [K + ] o . 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET relaxed precontracted coronary vessels (EC 50 , 1×10 −6 mol/L). The four regioisomers were equally active. TEA, charybdotoxin, and high [K + ] o attenuated the EET relaxations. 11,12-EET hyperpolarized coronary smooth muscle cells from −37±0.2 to −59±0.3 mV. In the cell-attached mode of patch clamp, both 14,15-EET and 11,12-EET increased the open-state probability of a Ca 2+ -activated K + channel in coronary smooth muscle cells. This effect was blocked by TEA and charybdotoxin. These data support the hypothesis that the EETs are EDHFs.
Are Antimicrobial Goods for Consumers Worth the Cost?
Authors: Tom Reynolds
Journal: Annals of Internal Medicine (1997)

Currents15 September 1997Are Antimicrobial Goods for Consumers Worth the Cost?Tom ReynoldsTom ReynoldsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-6-199709150-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the late 1800s, recurrent outbreaks of cholera, diphtheria, and typhus triggered widespread public concern over domestic hygiene. Sensing a lucrative market, entrepreneurs designed newfangled toilets, sewer traps, window ventilators, and water filters.A century later, a new wave of infectious diseases is rekindling fears, and marketers are responding with antimicrobial products ranging from soap to toys to underwear. The number of new germ-fighting products has risen steadily over the past 5 years, from 36 in 1992 to 123 in 1996, according to Marketing Intelligence Service of Naples, New York.Some experts question the prudence of spending extra money-up to ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1997Volume 127, Issue 6Page: 497-498KeywordsAntimicrobialsBacteriaChildrenFoodFood and Drug AdministrationHabitsInfectious diseasesMicrobiologyPrevention, policy, and public healthSoaps Issue Published: 15 September 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract P3-13-04: The Role of <i>PSPHL</i> in Breast Cancer in African American Women
Authors: LA Field, S Rummel, CD Shriver, RE. Ellsworth
Journal: Cancer Research (2010)

Abstract Background: Younger age at diagnosis and poorer prognosis in African American women (AAW) with breast cancer have led to a number of studies evaluating gene expression differences in tumors from AAW compared to those from Caucasian women (CW). Studies have found that PSPHL expression is significantly higher not only in breast but also in prostate and endometrial tumors from African Americans compared to Caucasians. SNP rs6700 in the 3’ UTR of PSPHL has been found to correlate with expression. Here, we investigated how rs6700 affects PSPHL expression levels in AAW and CW with and without breast cancer. Methods: Genomic DNA was isolated from 74 women with (35 AAW and 39 CW) and 37 women without breast cancer (23 AAW and 14 CW). rs6700 was genotyped using TaqMan SNP Genotyping assay C__314922_10. PSPHL expression levels in breast tissue were measured in these same women using TaqMan Gene Expression assay Hs00863464_m1 using RNA isolated from laser microdissected breast tumor cells or normal breast tissue from women with or without breast cancer, respectively. Results: PSPHL expression in breast tumors from AAW was significantly higher than in CW (P = 6 x 10-6). The median fold change in expression in AAW was 42.2; while only 2 (6%) AAW had no detectable expression of PSPHL, 21/39 (54%) CW did not express PSPHL. The minor allele frequency (T) in AAW with breast cancer was 0.41 compared to 0.06 in CW with breast cancer. In both AAW and CW, median levels of PSPHL expression were lowest (15.45 in AAW, 0 in CW) in women with the C/Cgenotype. In addition, all patients whose tumors had no detectable PSPHL expression had the C/C genotype. In women without breast cancer, the C/C genotype was also correlated with lower PSPHL expression and was more frequent among CW compared to AAW (79% and 39%, respectively). Conclusions: PSPHL is more highly expressed in both diseased and normal breast tissue from AAW compared to CW and expression of PSPHL correlated with rs6700 genotypes. Although the function of PSPHL is unknown, it may function in cellular proliferation. Higher expression in AAW may, therefore, promote the development of tumors in AAW. It must be noted, however, that the frequency of the C allele is significantly lower in the African American population as a whole (53% vs. 92%); therefore, differences described here may reflect population differences rather than any specific contribution to breast cancer etiology. However, due to the higher expression of PSPHL in African Americans with other hormone-dependent cancers, its role in tumorigenesis requires further study. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-04.
Abstract A34: A regulatory role of beta-PIX in epidermal growth factor-induced cancer cell migration
Authors: Jean-Cheng Kuo
Journal: Cancer Research (2013)

Abstract Expression of epidermal growth factor receptor (EGFR) in non–small cell lung cancer (NSCLC) tumors correlates with poor prognosis. EGFR signaling is Src dependent. Activation of EGFR leads to cycles of membrane protrusion, cell adhesion, contraction, and retraction, therefore promoting cell migration. Here, we show a novel role of beta-PIX (Pak-interactive exchange factor) in EGFR-mediated NSCLC cell migration. EGFR signals through Src, which phosphorylates beta-PIX sequentially at two specific tyrosine residues, 442 and 595. Phosphorylation of beta-PIX at tyrosine 442 leads to activation of small GTPase Rac1, which promotes membrane protrusion and cell adhesion assembly around 5 min after EGF stimulation. After another 20 minutes, tyrosine 442 is dephosphorylated, while tyrosine 595 of beta-PIX is phosphorylated. Phosphorylation of tyrosine 595 results in activation of small GTPase RhoA, contraction generation, adhesion disassembly, and cell retraction. These data suggest that the phosphorylation-dephosphorylation cycle of beta-PIX at tyrosine 442 and 595 serves as a regulatory signal downstream of EGFR to control migration and invasion of NSCLC cells. Note: This abstract was not presented at the conference. Citation Format: Jean-Cheng Kuo. A regulatory role of beta-PIX in epidermal growth factor-induced cancer cell migration. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A34.
Treatment of Typhoid Fever.
Authors: Wm. Bayard Shields
Journal: JAMA (1895)

St. Francis, Ark., Jan. 8, 1895. <h3>To the Editor:</h3> —Having become interested last summer in Dr. Woodbridge's articles on the abortive treatment of typhoid fever, I determined to test it at the first opportunity. I had seen and assisted in treating quite a number of cases of typhoid fever in the Memphis City Hospital, having been an interne there for nearly two years, and have no recollection of any cases being free from fever under three weeks, although treated according to the latest and most approved methods. Last fall I treated several cases according to Dr. Woodbridge's plan and was exceedingly pleased with the results. I did not succeed in cutting the disease so short as Dr. Woodbridge did, on account of the method being new to me, and for other reasons, only giving prescription No. 1 every hour for twenty-four hours, then the guaiacol and eucalyptol every three hours
The Royal College of Surgeons of England
Authors: J. W. Cousins
Journal: BMJ (1885)

I~~~-M ICAL JOUnN'-AL far as I can renmember, a single failure.The procedure was also circulated by the then Surgeon-General for the information aud guidance of all medical officers I must, lhowever, state that when I first came home fromii India in 1905 fxng-3skin grafting by my method (whlich is that now described by Captain Kendall) was given a trial at the Radcliffe Infirmary in Oxford by one of the surgeons, Lieutenant-Colonel Dodds-Parker, now senior surgeon of the 3id Southern General Hospital, which I have the honour to command.It proved a complete failure.In my opinion this failure resulted from the epidermal cells of the British frog failing to accommodate themselves to the normal body temperature of the human being.In this view tlhe 1ate Professor Jenkinson of this university concured, and he made experiments to endeavour to aceclimatize tadpoles to the abnormally high temperature, but withont success.It is encouraging to learn that Captain Kendall has met witlh success in his frog skin in France, in view of the failure witlh English frogs above mentioned.-Iam, etc.,
Doctors and Their Workshops: Economic Models of Physician Behavior
Authors: Harold S. Luft
Journal: JAMA (1981)

The jacket cover of<i>Doctors and Their Workshops</i>states that the book "will be of particular interest to economists, sociologists, health-services researchers, health-care providers, and planners of health-care programs and insurance policies." This is true, but for sharply divergent reasons. The book's subtitle, "Economic Models of Physician Behavior," is quite accurate, and Pauly is an expert practitioner of economic theory (model building) and hypothesis testing. This brief book includes several chapters outlining theoretical models of physician behavior that take into consideration the symbiotic relation of physicians and hospitals. The author also provides empirical tests of the models. Based on this work, Pauly reaches several important conclusions, for instance: (1) the amount of time physicians spend in hospitals is an important determinant of hospital expenditures; (2) physicians can allocate medical resources efficiently and appropriate fee schedules will lead to an optimal allocation of resources; (3) increased physician supply may lead physicians
Characterization of apocytochrome C binding to human erythrocytes
Authors: Gomathi Krishnan, Roderick D. MacGregor, Stephen B. Shohet, C. Anthony Hunt
Journal: American Journal of Hematology (1994)

The binding of 125I-labeled apocytochrome c to human erythrocytes was determined for free apocytochrome c concentrations at 10(-10)-10(-6) M. At about 2 x 10(-9) M, maximum cell association of apocytochrome c occurs at 50 mM NaCl and at 22 degrees C. Intact erythrocytes at 22 degrees C have three classes of apocytochrome c binding sites: one high-affinity noncooperative site (n1 = 728 per cell, Kd1 = 1.5 x 10(-9) M) and two positively cooperative sites (n2 = 3.7 x 10(4) per cell, Kd2 = 1.2 x 10(-7) M, alpha 2 = 2.0, and n3 = 2.5 x 10(5) per cell, Kd3 = 7.1 x 10(-7) M, alpha 3 = 12). Erythrocytes at 37 degrees C, and erythrocyte ghosts at 22 degrees C, also have three classes of apocytochrome c binding sites, and most sites are positively cooperative.
Mechanism of E2F1-induced apoptosis in primary vascular smooth muscle cells
Authors: J STANELLE, T STIEWE, F RODICKER, K KOHLER, C THESELING, B PUTZER
Journal: Cardiovascular Research (2003)

Objective: The transcription factor E2F1 serves as a major regulator of the cell-cycle by controlling G1-S phase transition. However, apart from its proliferative function high levels of deregulated E2F1 are capable of inducing apoptosis depending on the cellular context. In particular the tumor suppressor p53 and its homologue p73 are implicated in this proapoptotic function. Methods: Here, we investigated the mechanistic basis for E2F1-mediated apoptosis in vascular smooth muscle cells (VSMCs) which have previously been shown to be E2F1-responsive. Results: Interestingly, E2F1-expression in these cells induced clear signs of apoptosis in the absence of any proliferative activity. Although cell-cycle regulated genes such as CCNE1 and CDC25A were activated, BrdU-staining revealed no S-phase entry. Instead, a rapid loss of cell viability by induction of apoptosis was observed. Using a transactivation-defective E2F1-mutant, we show that apoptosis induction is independent of the transactivation function and therefore independent of ARF and p73. However, this mutant retains its ability to stabilize and phosphorylate p53, suggesting that p53 is sufficient for the effect of E2F1. Conclusion: VSMCs therefore represent a cellular system in which the transactivation-independent, proapoptotic activity of E2F1 is the primary cellular function. Ectopic expression of E2F1 might therefore be a suitable therapy to prevent VSMC hyperproliferation.
Toxicogenomics Data: The Road to Acceptance
Authors: Kris Freeman
Journal: Environmental Health Perspectives (2004)

Regulatory agencies believe microarray data could be extremely useful in testing prospective chemical products and investigating safety problems after chemicals have been marketed. However, it has not yet been clearly established how this information will be used by agencies in the approval of pharmaceuticals and other chemicals--or even whether companies will be required to submit microarray data. Although some private companies are already voluntarily submitting microarray data along with their drug and pesticide applications, others are hesitant to do so. Most of the stakeholders involved agree that standardization of microarray experiment procedures and of genomic signatures are key to the broad acceptance and use of these data.
Locus equation and hidden parameters of speech
Authors: Li Deng
Journal: Behavioral and Brain Sciences (1998)

Locus equations contain an economical set of hidden (i.e., not directly observable in the data) parameters of speech that provide an elegant way of characterizing the ubiquitous context-dependent behaviors exhibited in speech acoustics. These hidden parameters can be effectively exploited to constrain the huge set of context-dependent speech model parameters currently in use in modern, mainstream speech recognition technology.
Optimal detection of the progression of coronary artery disease: comparison of methods suitable for risk factor intervention trials.
Authors: S Ellis, W Sanders, C Goulet, R Miller, K C Cain, J Lesperance, M G Bourassa, E L Alderman
Journal: Circulation (1986)

To assess the best method of quantitating progression of coronary disease, we studied four measurements in 114 coronary segments from 35 medically treated patients from whom angiograms were obtained 5 years apart. Only stenoses of less than 70% that were visualized in nearly identical projections on both angiograms were evaluated. Vessel edges were measured by use of catheter calibration and an automated computer algorithm yielding two "absolute dimensions" (mean and minimum diameters) and two measurements (percent stenosis and atheroma area) that required a "normal reference" diameter. The coefficient of variation for repeated segment measurements was less for mean and minimum diameter than for percent stenosis and area of atheroma. The best measure of progression of coronary disease as determined by t test comparison of different methods was the change in mean diameter over time (6.7 +/- 14.1% decrease), whether calculated on a per coronary segment or per patient basis (p less than .001). Based on this measurement and its standard deviation of progression of coronary disease in this patient subset with relatively benign disease, it is estimated that 470 patients per group would be required for an interventional study to demonstrate a 33% reduction in disease progression (207 patients for 50% reduction) at a 95% confidence level and 90% power.