tbuckley/cabot-search huggingface dataset:
Weight Gain and Gestational Diabetes Mellitus Is a Sensitive Issue
Authors: Wendy C. Bevier, Lois Jovanovič
Journal: Diabetes Care (2007)

Is a Sensitive Issue Normal pregnancy is associated with reduced insulin sensitivity, compensatory increase in insulin secretion, and small changes in circulating nutrients.Gestational diabetes mellitus (GDM) occurs when insulin secretion is insufficient to compensate for the insulin resistance of pregnancy.During late pregnancy, women with GDM tend to be more insulin resistant than obesity-matched women with normal glucose tolerance (1).Little is known about the effects of weight gain in the third trimester versus no weight gain or weight loss as treatments for GDM.The objective of our study was to determine the effect of medical nutrition therapy (MNT) on insulin sensitivity (S i ), glucose effectiveness (S g ), glucose tolerance (K g ), and acute insulin response to intravenous glucose (AIR g ) in women with GDM in relation to weight gained or lost during treatment.A total of 20 women with GDM were prescribed MNT (40% carbohydrate, 40% fat, and 20% protein) (2) to achieve euglycemia.Caloric requirements were based on present pregnant weight.Women performed self-monitored blood glucose, fasting and 1 h postprandially, and visited the clinic weekly.
Tumor-Infiltrating Macrophages Are Associated with Metastasis Suppression in High-Grade Osteosarcoma: A Rationale for Treatment with Macrophage Activating Agents
Authors: Emilie P. Buddingh, Marieke L. Kuijjer, Ronald A.J. Duim, Horst Bürger, Konstantin Agelopoulos, Ola Myklebost, Massimo Serra, Fredrik Mertens, Pancras C.W. Hogendoorn, Arjan C. Lankester, Anne-Marie Cleton-Jansen
Journal: Clinical Cancer Research (2011)

High-grade osteosarcoma is a malignant primary bone tumor with a peak incidence in adolescence. Overall survival (OS) of patients with resectable metastatic disease is approximately 20%. The exact mechanisms of development of metastases in osteosarcoma remain unclear. Most studies focus on tumor cells, but it is increasingly evident that stroma plays an important role in tumorigenesis and metastasis. We investigated the development of metastasis by studying tumor cells and their stromal context.To identify gene signatures playing a role in metastasis, we carried out genome-wide gene expression profiling on prechemotherapy biopsies of patients who did (n = 34) and patients who did not (n = 19) develop metastases within 5 years. Immunohistochemistry (IHC) was performed on pretreatment biopsies from 2 additional cohorts (n = 63 and n = 16) and corresponding postchemotherapy resections and metastases.A total of 118/132 differentially expressed genes were upregulated in patients without metastases. Remarkably, almost half of these upregulated genes had immunological functions, particularly related to macrophages. Macrophage-associated genes were expressed by infiltrating cells and not by osteosarcoma cells. Tumor-associated macrophages (TAM) were quantified with IHC and associated with significantly better overall survival (OS) in the additional patient cohorts. Osteosarcoma samples contained both M1- (CD14/HLA-DRα positive) and M2-type TAMs (CD14/CD163 positive and association with angiogenesis).In contrast to most other tumor types, TAMs are associated with reduced metastasis and improved survival in high-grade osteosarcoma. This study provides a biological rationale for the adjuvant treatment of high-grade osteosarcoma patients with macrophage activating agents, such as muramyl tripeptide.
Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy
Authors: Anne G Semb, Sanne van Wissen, Thor Ueland, Tineke Smilde, Torgun Waehre, Mieke D Tripp, Stig S Frøland, John J.P Kastelein, Lars Gullestad, Terje R Pedersen, P.ål Aukrust, Anton F.H Stalenhoef
Journal: Journal of the American College of Cardiology (2003)
Simvastatin in the Acute Respiratory Distress Syndrome
Authors: Daniel F. McAuley, John G. Laffey, Cecilia M. O'Kane, Gavin D. Perkins, Brian Mullan, T. John Trinder, Paul Johnston, Philip A. Hopkins, Andrew J. Johnston, Cliona McDowell, Christine McNally
Journal: New England Journal of Medicine (2014)

Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety.The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug.Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.).
Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials
Authors: Funda Meric-Bernstam, Lauren Brusco, Kenna Shaw, Chacha Horombe, Scott Kopetz, Michael A. Davies, Mark Routbort, Sarina A. Piha-Paul, Filip Janku, Naoto Ueno, David Hong, John De Groot, Vinod Ravi, Yisheng Li, Raja Luthra, Keyur Patel, Russell Broaddus, John Mendelsohn, Gordon B. Mills
Journal: Journal of Clinical Oncology (2015)

We report the experience with 2,000 consecutive patients with advanced cancer who underwent testing on a genomic testing protocol, including the frequency of actionable alterations across tumor types, subsequent enrollment onto clinical trials, and the challenges for trial enrollment.Standardized hotspot mutation analysis was performed in 2,000 patients, using either an 11-gene (251 patients) or a 46- or 50-gene (1,749 patients) multiplex platform. Thirty-five genes were considered potentially actionable based on their potential to be targeted with approved or investigational therapies.Seven hundred eighty-nine patients (39%) had at least one mutation in potentially actionable genes. Eighty-three patients (11%) with potentially actionable mutations went on genotype-matched trials targeting these alterations. Of 230 patients with PIK3CA/AKT1/PTEN/BRAF mutations that returned for therapy, 116 (50%) received a genotype-matched drug. Forty patients (17%) were treated on a genotype-selected trial requiring a mutation for eligibility, 16 (7%) were treated on a genotype-relevant trial targeting a genomic alteration without biomarker selection, and 40 (17%) received a genotype-relevant drug off trial. Challenges to trial accrual included patient preference of noninvestigational treatment or local treatment, poor performance status or other reasons for trial ineligibility, lack of trials/slots, and insurance denial.Broad implementation of multiplex hotspot testing is feasible; however, only a small portion of patients with actionable alterations were actually enrolled onto genotype-matched trials. Increased awareness of therapeutic implications and access to novel therapeutics are needed to optimally leverage results from broad-based genomic testing.
Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study
Authors: Anita D'Souza, Angela Dispenzieri, Baldeep Wirk, Mei-Jie Zhang, Jiaxing Huang, Morie A. Gertz, Robert A. Kyle, Shaji Kumar, Raymond L. Comenzo, Robert Peter Gale, Hillard M. Lazarus, Bipin N. Savani, Robert F. Cornell, Brendan M. Weiss, Dan T. Vogl, César O. Freytes, Emma C. Scott, Heather J. Landau, Jan S. Moreb, Luciano J. Costa, Muthalagu Ramanathan, Natalie S. Callander, Rammurti T. Kamble, Richard F. Olsson, Siddhartha Ganguly, Taiga Nishihori, Tamila L. Kindwall-Keller, William A. Wood, Tomer M. Mark, Parameswaran Hari
Journal: Journal of Clinical Oncology (2015)

Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America.
Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA.
Authors: M A Iñiguez, A Rodriguez-Peña, N Ibarrola, G Morreale de Escobar, J Bernal
Journal: Journal of Clinical Investigation (1992)

The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods" of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Muñoz, A., A. Rodriguez-Peña, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a decreased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in either experimental situation. RC3 mRNA levels were not affected by food restriction demonstrating that the effect of hypothyroidism was not related to the lack of weight gain. The control of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations induced by hypothyroidism in the adult brain.
791 Contractile response of femoral arteries in pigs with acute liver failure
Authors: L YTREBO, S EKSE, S SEN, C ROSE, O FUSKEV, G NEDREDAL, R JALAN, A REVHAUG
Journal: Hepatology (2003)

Background: Acute liver failure (ALF) is characterized haemodynamically by a progressive hyperdynamic circulation.The pathophysiological mechanism is unknown, but impaired contractility of vascular smooth muscle may play an important role.The aim of this study was to evaluate the vascular response to stimulation with norepinephrine and angiotensin II in endothelium-denuded femoral artery rings.Methods: Norwegian Landrace pigs weighing 27.1 ± 0.5 kg (mean ± s x (standard error of the mean)) were used.ALF was induced by performing a portacaval shunt followed by ligation of the hepatic arteries (n = 6).Sham-operated animals served as controls (n = 5).Cumulative isometric concentration contraction curves were obtained after in vitro stimulation of the femoral artery rings with either angiotensin II (10 -13 -10 -5 mol/L) or norepinephrine (10 -13 -10 -3 mol/L).Results: Pigs suffering from ALF developed a hyperdynamic circulation with an increased cardiac index (P = 0.017) and decreased systemic vascular resistance index (P = 0.015).Studies of the hind leg revealed a decreased vascular resistance index and increased blood flow compared to sham-operated controls (P = 0.003 and P = 0.01, respectively).Angiotensin II caused a concentration-dependent contraction of the arterial segments, with no significant differences in vascular responses between the two groups.Maximum force generated did not differ (55 ± 7 versus 56 ± 7 mN, P = 0.95).Furthermore, there were no differences for norepinephrine in the cumulative concentration-response curves and the maximum contractile force was not significantly different (87 ± 8 versus 93 ± 16 mN, P = 0.55).Conclusions: This study documents for the first time that there are no signs of endothelium-independent peripheral vascular hyporesponsiveness to angiotensin II and norepinephrine in pigs with ALF.
Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling
Authors: T. Kohno, T. Anzai, K. Naito, T. Miyasho, M. Okamoto, H. Yokota, S. Yamada, Y. Maekawa, T. Takahashi, T. Yoshikawa, A. Ishizaka, S. Ogawa
Journal: Cardiovascular Research (2008)

AimsHigh-mobility group box 1 protein (HMGB1) is one of the recently defined damage-associated molecular pattern molecules derived from necrotic cells and activated macrophages. We investigated clinical implications of serum HMGB1 elevation in patients with acute myocardial infarction (MI). Then, we evaluated the effect of HMGB1 blockade on post-MI left ventricular (LV) remodelling in a rat MI model.
The Severity of Secondary Hyperparathyroidism in Chronic Renal Insufficiency is GFR-Dependent, Race-Dependent, and Associated with Cardiovascular Disease
Authors: Ian H. de Boer, Irina Gorodetskaya, Belinda Young, Chi-yuan Hsu, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Secondary hyperparathyroidism (SHPT) is an important complication of end-stage renal disease. However, SHPT begins during earlier stages of chronic renal insufficiency (CRI), and little is known about risk factors for SHPT in this population. This study evaluated 218 patients in an ethnically diverse ambulatory nephrology practice at the University of California San Francisco during calendar years 1999 and 2000. Demographic data, comorbid diseases, medications, and laboratory parameters were collected, and independent correlates of intact parathyroid hormone (PTH) were identified by using multiple linear regression. The mean estimated GFR was 34 ml/min per 1.73 m2 (10%–90% range, 13 to 61 ml/min per 1.73 m2); PTH was inversely related to GFR (P < 0.0001). The adjusted mean PTH was higher among African Americans and lower among Asian/Pacific Islanders compared with white patients (233 versus 95 versus 139 pg/ml; P < 0.0001). Moreover, among the 196 patients with GFR <60 ml/min per 1.73 m2, the slope of GFR versus PTH was significantly steeper among African Americans than among white patients (10.6 versus 3.9 pg/ml per ml per min per 1.73 m2; P = 0.01). After adjusting for age and diabetes, PTH was associated with a history of myocardial infarction (OR, 1.6; 95% CI, 1.1 to 2.3 per unit natural log PTH) and congestive heart failure (OR, 2.0; 95% CI, 1.3 to 2.9 per unit natural log PTH) and not associated with other co-morbid conditions. These factors should be considered when screening and managing SHPT in CRI.
Adiponectin is a novel humoral vasodilator
Authors: G FESUS, G DUBROVSKA, K GORZELNIAK, R KLUGE, Y HUANG, F LUFT, M GOLLASCH
Journal: Cardiovascular Research (2007)

Objectives Perivascular adipose tissue secretes an adipocyte-derived relaxing factor(s) (ADRF) that opens Kv channels in rat arteries. Visceral fat accumulation causes adipocyte dysfunction, including hyposecretion of adiponectin. We tested the hypothesis that ADRF might be adiponectin and that adiponectin plays a role in the paracrine control of vascular tone by perivascular adipose tissue.
A Novel Mechanism of Resistance to Epidermal Growth Factor Receptor Antagonism <i>In vivo</i>
Authors: Ashwani Rajput, Alan P. Koterba, Jeffrey I. Kreisberg, Jason M. Foster, James K.V. Willson, Michael G. Brattain
Journal: Cancer Research (2007)

Abstract Epidermal growth factor receptor (EGFR) is widely expressed in a number of solid tumors including colorectal cancers. Overexpression of this receptor is one means by which a cell can achieve positive signals for survival and proliferation; another effective means is by constitutive activation of EGFR. We have elucidated the role of constitutive EGFR signaling in malignant progression by stably transfecting colon cancer cells with a human transforming growth factor-α cDNA (a ligand for EGFR) under repressible control by tetracycline. We show that constitutive expression of transforming growth factor-α and its subsequent constitutive activation of EGFR allows for cancer cell survival in response to environmental stress in vitro and in vivo as well. The reversal of constitutive EGFR activation results in the loss of downstream mitogen-activated protein kinase and Akt activation, and a reduction in xenograft size that is associated with decreased proliferation and increased apoptosis. We used CI-1033, a small molecule antagonist of EGFR, to dissect an activation pathway that shows the ability of ERBb2 to activate Akt, but not Erk in the face of EGFR antagonism. This novel escape mechanism is a possible explanation of why anti-EGFR therapies have shown disappointing results in clinical trials. [Cancer Res 2007;67(2):665–73]
The effect of complement on the ingestion of soluble antigen-antibody complexes and IgM aggregates by mouse peritoneal macrophages.
Authors: J L van Snick, P L Masson
Journal: The Journal of Experimental Medicine (1978)

Complement was found to stimulate markedly the ingestion of soluble antigen-antibody complexes by mouse peritoneal macrophages. This was shown indirectly by measuring the release of degradation products when the complexes were labeled with 125I, or directly when the antigen, that was human transferrin, was labeled with 59Fe. In this case, the metal which was released from human transferrin inside the cells was not excreted, and its accumulation in the macrophages was a direct index of the uptake of immune complexes. The decay of radioactivity in macrophages after ingestion of 125I-labeled complexes was similar when they were taken up with or without complement, indicating that complement acts primarily on ingestion and not on digestion or excretion. The ingestion of complexes was morphologically confirmed using fluorescein-labeled antigen in the immune complexes. The opsonic effect of complement was also observed with IgM aggregates indicating that soluble complexes can be ingested through complement receptors without involvement of Fc-receptors, as required for particulate antigen-antibody complexes.
Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy
Authors: Julie Wang, Stacie M. Jones, Jacqueline A. Pongracic, Ying Song, Nan Yang, Scott H. Sicherer, Melanie M. Makhija, Rachel G. Robison, Erin Moshier, James Godbold, Hugh A. Sampson, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2015)
Dual vs Single Protease Inhibitor Therapy Following Antiretroviral Treatment Failure&lt;SUBTITLE&gt;A Randomized Trial&lt;/SUBTITLE&gt;
Authors: Scott M. Hammer
Journal: JAMA (2002)

Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge.To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen.Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks.Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States.A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL.Selectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n = 69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil.Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility.Of 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P =.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270] vs 16% [33/211], respectively; P<.001). Baseline HIV-1 hypersusceptibility to efavirenz (< or = 0.4-fold difference in susceptibility compared with reference virus) was associated with suppression of viral load at 24 weeks to below 200 copies/mL (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.62-7.33; P =.001), and more than 10-fold reduction in efavirenz susceptibility, with less likelihood of suppression at 24 weeks (OR, 0.28; 95% CI, 0.09-0.87; P =.03).In this study of antiretroviral-experienced patients with advanced immunodeficiency, viral load suppression to below 200 copies/mL was achieved in 31% of patients with regimens containing 4 or 5 new drugs. Use of 2 PIs, being naive to NNRTIs, and baseline hypersusceptibility to efavirenz were associated with a favorable outcome.
Evidence for a functional interaction between the beta chain of major histocompatibility complex class II and the T cell receptor alpha chain during recognition of a bacterial superantigen.
Authors: A M Deckhut, Y Chien, M A Blackman, D L Woodland
Journal: The Journal of Experimental Medicine (1994)

Several studies have suggested that there is a direct interaction between the T cell receptor (TCR) and the major histocompatibility complex (MHC) molecule during T cell recognition of superantigen. To further investigate this possibility, we have analyzed T cell recognition of a bacterial superantigen, Staphylococcal enterotoxin B (SEB), presented by a series of mutant murine I-Ek molecules in which residues of either the alpha or beta chain predicted to interact with the TCR have been substituted. Individual T cell hybridomas gave distinct patterns of responsiveness to SEB presented by the I-E beta k mutants that could not be attributed to differences in the binding of SEB to the mutants. This effect appeared to be dependent on the TCR-alpha chain because some of these hybridomas expressed identical TCR transgenic beta chains. In contrast, none of the hybridomas gave distinct patterns of responsiveness to SEB presented by the I-E alpha k mutants. Taken together, these observations support the idea that there is a functional interaction between the alpha chain of the TCR and the beta chain of the MHC class II molecule. The data also support the idea that this interaction might enhance superantigen recognition in some cases.