tbuckley/cabot-search huggingface dataset:
Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors
Authors: J.-C. Soria, F. DeBraud, R. Bahleda, B. Adamo, F. Andre, R. Dientsmann, A. Delmonte, R. Cereda, J. Isaacson, J. Litten, A. Allen, F. Dubois, C. Saba, R. Robert, M. D'Incalci, M. Zucchetti, M.G. Camboni, J. Tabernero
Journal: Annals of Oncology (2014)
Disparate Patterns of Aldosterone Response During Diuretic Treatment of Hypertension
Authors: MICHAEL A. WEBER
Journal: Annals of Internal Medicine (1977)

In 50 patients with essential hypertension treated with chlorthalidone, 100 mg daily for 6 weeks, treatment responders (fall in mean pressure, ≥ 10%) and nonresponders experienced similar weight and electrolyte changes. Although induced increments and post-treatment values of plasma renin were higher in nonresponders than responders, there was a far more striking difference in aldosterone reactivity. Aldosterone excretion rose by less than 10% in the responders but almost doubled in the nonresponders. Again, within the normal renin subgroup alone (n=28), nonresponders exhibited control renin values and treatment-induced changes in plasma renin closely similar to those in responders, but experienced a significantly greater increase in aldosterone excretion. Possibly this increase in aldosterone produced subtle volume retention or a direct pressor effect in nonresponding patients. Although changes in aldosterone and in renin correlated with each other in both responders and nonresponders, the slopes of the regression lines in the two groups differed significantly. Thus, cofactors governing sensitivity of the aldosterone response to renin stimulation ultimately may determine the anthihypertensive effectiveness of diuretics.
Phase II Study of Efficacy, Safety, and Pharmacokinetics of Trastuzumab Monotherapy Administered on a 3-Weekly Schedule
Authors: José Baselga, Xavier Carbonell, Noel-Jaime Castañeda-Soto, Michael Clemens, Michael Green, Vernon Harvey, Serafin Morales, Claire Barton, Parviz Ghahramani
Journal: Journal of Clinical Oncology (2005)

Purpose This phase II study investigated the efficacy, safety, and pharmacokinetics of trastuzumab monotherapy given as first-line treatment once every 3 weeks (3-weekly) in women with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Patients and Methods Patients with previously untreated HER2-positive MBC received a loading dose of trastuzumab, 8 mg/kg intravenously (IV) and then 6 mg/kg IV at 3-week intervals until disease progression or patient withdrawal. Results In total, 105 patients received a median of five cycles of therapy (range, 1 to 35+). The overall response rate was 19% (23% in patients with measurable centrally confirmed immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] -positive disease) and clinical benefit rate (complete and partial responses plus stable disease for at least 6 months) was 33% (36% in patients with measurable centrally confirmed IHC 3+ and/or FISH-positive disease). Median time to progression was 3.4 months (range, 0.6 to 23.6 months). The most common treatment-related adverse events were rigors, pyrexia, headache, nausea, and fatigue. Median baseline left ventricular ejection fraction was 63%; this did not significantly change over the course of the study. The average exposure to trastuzumab observed in this study was similar to that in previous studies of the weekly regimen. However, as expected, mean trough trastuzumab concentrations were lower and peak levels were higher with 3-weekly trastuzumab compared with weekly treatments. Conclusion Administering higher doses on a 3-weekly schedule did not compromise the efficacy and safety of trastuzumab in women with HER2-positive MBC, and average exposure was similar to that observed with weekly therapy. Three-weekly trastuzumab may represent a convenient alternative to weekly administration.
Helper function of T cells depleted of alloantigen-reactive lymphocytes by filtration through irradiated F1 hybrid recipients. I. Failure to collaborate with allogeneic B cells in a secondary response to sheep erythrocytes measured in vivo.
Authors: J Sprent, H von Boehmer
Journal: The Journal of Experimental Medicine (1976)

Helper T cells were obtained by injecting heavily irradiated semiallogeneic mice with lymph node cells from H-2-incompatible parental strain mice primed with sheep erythrocytes (SRC) 2 mo before. Thoracic duct lymphocytes collected from the recipents 18-40 h later (nearly all of which were theta-positive and of donor origin) were totally and specifically unresponsive against host-type determinants in mixed-lymphocyte culture. The filtered cells were transferred to irradiated semiallogeneic mice together with SRC and anti-theta-serum-treated (B) cells from SRC-primed syngeneic, semiallogeneic, or allogeneic mice. When antibody-forming cells were measured in the spleen 5-9 days later, effective IgM and IgG collaborative responses were observed with both syngeneic and semiallogeneic B cells but not with allogeneic B cells. No evidence was found that the failure to obtain collaboration with the allogeneic B cells was due to inhibition of the B cells by the T cells or vice versa.
Cellular engineering of ventricular adult rat cardiomyocytes
Authors: C Weikert
Journal: Cardiovascular Research (2003)

Preparation of viable cultured adult cardiomyocytes (vARCs) is a prerequisite for cell-based transplantation and tissue engineering. Ectopic gene expression is important in this context. Here, we present an in vitro cell replating strategy using Accutase for cultured vARCs, allowing ectopic gene expression.Cultured vARCs from 6- to 8-week-old rats were used. Transfections with EGFP (enhanced green fluorescent protein) constructs, Mlc-3f-EGFP or alpha-actinin-EGFP were performed using adenovirus-enhanced transferrin-mediated infection (AVET). Accutase (PAA Laboratories, Linz, Austria) was used for the detachment of cultured cells. Immunohistochemical analysis, together with confocal laser microscopy was used for structural analysis of the cells.Cultured vARCs could be detached with a high yield (40 to 60%) from primary cultures using Accutase. The cultivation period plays an important role in the yield of viable cells. Resultant replated vARCs (rep-vARCs) rapidly (1-2 h) acquired a rounded up shape without degradation of their contractile apparatus, which is in contrast to the rod-shaped freshly isolated vARCs (fi-vARCs). The detached cells survived passage through a narrow syringe needle. After seeding, detached cells rapidly attached to various substrates, increased their content of the contractile apparatus, and formed cell-cell contacts within 3 days after reseeding. The detached cells survived passage through a narrow syringe needle. The high recovery of cells after replating enabled the use of the AVET system for gene delivery. AVET is free of infectious particles and does not lead to expression of viral proteins. Transfection of vARCs prior to detachment had a small effect on cell recovery and ectopically synthesized proteins were properly localized after replating.Detachment of cultured vARCs using Accutase is well compatible with ectopic gene expression and yields a viable transgenic population of vARCs that eventually may be suitable as transgenic cardiomyocyte grafts.
Effect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women
Authors: Makiko Yoshida, Paul F. Jacques, James B. Meigs, Edward Saltzman, M. Kyla Shea, Caren Gundberg, Bess Dawson-Hughes, Gerard Dallal, Sarah L. Booth
Journal: Diabetes Care (2008)

OBJECTIVE—Vitamin K has a potentially beneficial role in insulin resistance, but evidence is limited in humans. We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women. RESEARCH DESIGN AND METHODS—This was an ancillary study of a 36-month, randomized, double-blind, controlled trial designed to assess the impact of supplementation with 500 μg/day phylloquinone on bone loss. Study participants were older nondiabetic men and women (n = 355; aged 60–80 years; 60% women). The primary outcome of this study was insulin resistance as measured by homeostasis model assessment (HOMA-IR) at 36 months. Fasting plasma insulin and glucose were examined as the secondary outcomes. RESULTS—The effect of 36-month vitamin K supplementation on HOMA-IR differed by sex (sex × treatment interaction P = 0.02). HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group versus the men in the control group (P = 0.01) after adjustment for baseline HOMA-IR, BMI, and body weight change. There were no statistically significant differences in outcome measures between intervention groups in women. CONCLUSIONS—Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men.
ATM-dependent spontaneous regression of early Eμ-myc–induced murine B-cell leukemia depends on natural killer and T cells
Authors: J. Ludovic Croxford, Melissa Li Fang Tang, Meng Fei Pan, Caleb Weihao Huang, Neha Kamran, Cindy Meow Ling Phua, Wee Joo Chng, Siok Bian Ng, David H. Raulet, Stephan Gasser
Journal: Blood (2013)
Comparison of the effects of recombinant human insulin-like growth factor-I and insulin on glucose and leucine kinetics in humans.
Authors: R Laager, R Ninnis, U Keller
Journal: Journal of Clinical Investigation (1993)

To compare the metabolic effects of elevated plasma concentrations of IGF-I and insulin, overnight-fasted normal subjects were studied twice, once receiving IGF-I and once insulin at doses that resulted in identical increases in glucose uptake during 8-h euglycemic clamping. Recombinant human IGF-I or insulin were infused in one group at high doses (30 micrograms/kg per h IGF-I or 0.23 nmol/kg per h insulin) and in another group at low doses (5 micrograms/kg per h IGF-I or 0.04 nmol/kg per h insulin). Glucose rate of disappearance (measured by [6,6-D2]-glucose infusions) increased from baseline by 239 +/- 16% during high dose IGF-I vs 197 +/- 18% during insulin (P = 0.021 vs IGF-I). Hepatic glucose production decreased by 37 +/- 6% during high dose IGF-I vs 89 +/- 13% during insulin (P = 0.0028 vs IGF-I). IGF-I suppressed whole body leucine flux ([1-13C]-leucine infusion technique) more than insulin (42 +/- 4 vs 32 +/- 3% during high doses, P = 0.0082). Leucine oxidation rate decreased during high dose IGF-I more than during insulin (55 +/- 4 vs 32 +/- 6%, P = 0.0001). The decreases of plasma concentrations of free fatty acids, acetoacetate, and beta-hydroxybutyrate after 8 h of IGF-I and insulin administration were similar. Plasma C-peptide levels decreased by 57 +/- 4% during high doses of IGF-I vs 36 +/- 6% during insulin (P = 0.005 vs IGF-I). The present data demonstrate that, compared to insulin, an acute increase in plasma IGF-I levels results in preferential enhancement of peripheral glucose utilization, diminished suppression of hepatic glucose production, augmented decrease of whole body protein breakdown (leucine flux), and of irreversible leucine catabolism but in similar antilipolytic effects. The data suggest that insulin-like effects of IGF-I in humans are mediated in part via IGF-I receptors and in part via insulin receptors.
Mature B-cell lymphoma/leukemia in children and adolescents: Intergroup pathologist consensus with the Revised European—American Lymphoma Classification
Authors: M.A. Lones, A. Auperin, M. Raphael, K. McCarthy, S.L. Perkins, K.A. MacLennan, A. Ramsay, A. Wotherspoon, M. Gerrard, M.S. Cairo, C. Patte
Journal: Annals of Oncology (2000)
On Palsy of the Vocal Cord from Intracranial Syphilis
Authors: J. H. Jackson
Journal: BMJ (1873)

make the two following statements.I never anywhere said or sug- gested that a force of " four pounds" was required to pass a probe in a healthy woman, nor a force of even half a pound.Dr. Bennet's assertions as to the state of the healthy ora uteri, externum and internum, are, I am convinced, erroneous and inconsistent with anatomy, physi- ology, pathology, and daily experience.It is well-known that some gynmecologists speak and treat as if every woman suffering from dysmenorrhcea or sterility had a strictured cervix; but it is not necessary, in order to account for such proceedings, to resort to Dr. Bennet's dictum that the os uteri internum is normally closed during life, except at certain times.These remarks render it unnecessary for me-specially to consider the observations of Dr. Boulton; and those of Dr. Greenhaigh raise no question upon which I am called to make comment.I thank each of the gentlemen above referred to for their valued criticisms; and I end by saying that I believe the treatment of spasmodic dysmenorrhcea by mechanical means appears to me, at present, to be best effected by the use of a graduated series of metallic bougies, applied as I have elsewhere described-
U.S. Trends in Antiretroviral Therapy Use, HIV RNA Plasma Viral Loads, and CD4 T-Lymphocyte Cell Counts Among HIV-Infected Persons, 2000 to 2008
Authors: Keri N. Althoff, Kate Buchacz, H. Irene Hall, Jinbing Zhang, David B. Hanna, Peter Rebeiro, Stephen J. Gange, Richard D. Moore, Mari M. Kitahata, Kelly A. Gebo, Jeffrey Martin, Amy C. Justice, Michael A. Horberg, Robert S. Hogg, Timothy R. Sterling, Angela Cescon, Marina B. Klein, Jennifer E. Thorne, Heidi M. Crane, Michael J. Mugavero, Sonia Napravnik, Gregory D. Kirk, Lisa P. Jacobson, John T. Brooks
Journal: Annals of Internal Medicine (2012)

Background: The U.S. National HIV/AIDS Strategy targets for 2015 include "increasing access to care and improving health outcomes for persons living with HIV in the United States" (PLWH-US). Objective: To demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes. Design: Trends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states. Setting: U.S. HIV outpatient clinics. Patients: HIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008. Measurements: Annual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death. Results: 45 529 HIV-infected persons received care in an NA-ACCORD–participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001). Limitation: The usual limitations of observational data apply. Conclusion: The NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death. Primary Funding Source: National Institutes of Health; Centers for Disease Control and Prevention; Canadian Institutes of Health Research; Canadian HIV Trials Network; and the government of British Columbia, Canada.
AGRANULOCYTIC ANGINA FOLLOWING INGESTION OF DINITROPHENOL
Authors: S. STEPHEN BOHN
Journal: JAMA (1934)

During recent months the medical literature has been characterized by numerous reports of cases illustrating unfavorable reactions and deaths following the use of dinitrophenol, the barbiturates and amidopyrine. In the instances of these reactions following therapy with the barbiturates and amidopyrine, several observers have cited a resulting neutropenia or agranulocytic angina. There is reference made, however, to only one case of agranulocytic angina following the ingestion of dinitrophenol.<sup>1</sup>The report includes a case in which agranulocytosis developed after the ingestion of dinitrophenol over a period of two weeks, the patient recovering following treatment. Since no mention was made in this case regarding the amount of the drug taken during the two weeks or of the blood picture, and since in no other report of dinitrophenol poisoning has there been reference made to an ensuing neutropenia (those reports including a blood picture showed essentially normal white blood counts, while the
Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101)
Authors: P. Comella, G. Filippelli, G. De Cataldis, B. Massidda, G. Frasci, L. Maiorino, C. Putzu, S. Mancarella, S. Palmeri, R. Cioffi, M. Roselli, F. Buzzi, V. Milia, A. Gambardella, D. Natale, M. Bianco, M. Ghiani, P. Masullo
Journal: Annals of Oncology (2006)
Interleukin-12 Receptor/STAT4 Signaling Is Required for the Development of Autoimmune Myocarditis in Mice by an Interferon-γ–Independent Pathway
Authors: Marina Afanasyeva, Yan Wang, Ziya Kaya, Elizabeth A. Stafford, K. Malte Dohmen, Amir A. Sadighi Akha, Noel R. Rose
Journal: Circulation (2001)

Background — Interleukin (IL)-12 exerts a potent proinflammatory effect by stimulating T-helper (Th) 1 responses. This effect is believed to be mediated primarily through the activation of STAT4 and subsequent production of interferon (IFN)-γ. Methods and Results — We examined the role of IL-12 receptor (IL-12R) signaling in the development of murine experimental autoimmune myocarditis (EAM) induced by cardiac myosin immunization. Both IL-12Rβ1–deficient mice and STAT4-deficient mice were resistant to the induction of myocarditis. Treatment with exogenous IL-12 exacerbated disease. We questioned whether IFN-γ is required for the disease-promoting activity of IL-12. On the contrary, we found that IFN-γ suppresses EAM. Lack of IFN-γ due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis. Spleens from IFN-γ–deficient mice immunized with cardiac myosin showed increased cellularity; greater numbers of CD3+, CD4+, CD8+, and IL-2–producing cells; and heightened ability to produce cytokines on stimulation in vitro. Treatment of mice with recombinant IFN-γ suppressed the development of myocarditis. Conclusions — IL-12 / IL-12R/STAT4 signaling promotes the development of EAM. In contrast, IFN-γ plays a protective role. The disease-limiting effects of IFN-γ might be explained by its ability to control the expansion of activated T lymphocytes.
Phylodynamic Inference with Kernel ABC and Its Application to HIV Epidemiology
Authors: Art F.Y. Poon
Journal: Molecular Biology and Evolution (2015)

The shapes of phylogenetic trees relating virus populations are determined by the adaptation of viruses within each host, and by the transmission of viruses among hosts. Phylodynamic inference attempts to reverse this flow of information, estimating parameters of these processes from the shape of a virus phylogeny reconstructed from a sample of genetic sequences from the epidemic. A key challenge to phylodynamic inference is quantifying the similarity between two trees in an efficient and comprehensive way. In this study, I demonstrate that a new distance measure, based on a subset tree kernel function from computational linguistics, confers a significant improvement over previous measures of tree shape for classifying trees generated under different epidemiological scenarios. Next, I incorporate this kernel-based distance measure into an approximate Bayesian computation (ABC) framework for phylodynamic inference. ABC bypasses the need for an analytical solution of model likelihood, as it only requires the ability to simulate data from the model. I validate this "kernel-ABC" method for phylodynamic inference by estimating parameters from data simulated under a simple epidemiological model. Results indicate that kernel-ABC attained greater accuracy for parameters associated with virus transmission than leading software on the same data sets. Finally, I apply the kernel-ABC framework to study a recent outbreak of a recombinant HIV subtype in China. Kernel-ABC provides a versatile framework for phylodynamic inference because it can fit a broader range of models than methods that rely on the computation of exact likelihoods.
Phenotypic variability associated with<i>WNT10A</i>nonsense mutations
Authors: M. Van Geel, M. Gattas, Y. Kesler, P. Tong, H. Yan, K. Tran, P.M. Steijlen, D.F. Murrell, M.A.M. Van Steensel
Journal: British Journal of Dermatology (2010)

Journal Article Phenotypic variability associated with WNT10A nonsense mutations Get access M. Van Geel, M. Van Geel Department of Dermatology, Maastricht University Medical Center, PO Box 5800, 6202AZ Maastricht, the NetherlandsGROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M. Gattas, M. Gattas Department of Paediatrics and Child Health, University of Queensland, Brisbane, Queensland, Australia Search for other works by this author on: Oxford Academic Google Scholar Y. Kesler, Y. Kesler Department of Dermatology, Maastricht University Medical Center, PO Box 5800, 6202AZ Maastricht, the NetherlandsGROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P. Tong, P. Tong Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia Search for other works by this author on: Oxford Academic Google Scholar H. Yan, H. Yan Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia Search for other works by this author on: Oxford Academic Google Scholar K. Tran, K. Tran Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia Search for other works by this author on: Oxford Academic Google Scholar P.M. Steijlen, P.M. Steijlen Department of Dermatology, Maastricht University Medical Center, PO Box 5800, 6202AZ Maastricht, the NetherlandsGROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar D.F. Murrell, D.F. Murrell Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia Search for other works by this author on: Oxford Academic Google Scholar M.A.M. Van Steensel M.A.M. Van Steensel Department of Dermatology, Maastricht University Medical Center, PO Box 5800, 6202AZ Maastricht, the NetherlandsGROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, the Netherlands M.A.M. van Steensel. E‐mail: m.van.steensel@mumc.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 6, 1 June 2010, Pages 1403–1406, https://doi.org/10.1111/j.1365-2133.2010.09703.x Published: 01 June 2010