tbuckley/cabot-search huggingface dataset:
Blockade of T Lymphocyte Costimulation with Cytotoxic T Lymphocyte–Associated Antigen 4–Immunoglobulin (Ctla4ig) Reverses the Cellular Pathology of Psoriatic Plaques, Including the Activation of Keratinocytes, Dendritic Cells, and Endothelial Cells
Authors: Judith R. Abrams, Susan L. Kelley, Elizabeth Hayes, Toyoko Kikuchi, Michael J. Brown, Sewon Kang, Mark G. Lebwohl, Cynthia A. Guzzo, Brian V. Jegasothy, Peter S. Linsley, James G. Krueger
Journal: The Journal of Experimental Medicine (2000)

Efficient T cell activation is dependent on the intimate contact between antigen-presenting cells (APCs) and T cells. The engagement of the B7 family of molecules on APCs with CD28 and CD152 (cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) receptors on T cells delivers costimulatory signal(s) important in T cell activation. We investigated the dependence of pathologic cellular activation in psoriatic plaques on B7-mediated T cell costimulation. Patients with psoriasis vulgaris received four intravenous infusions of the soluble chimeric protein CTLA4Ig (BMS-188667) in a 26-wk, phase I, open label dose escalation study. Clinical improvement was associated with reduced cellular activation of lesional T cells, keratinocytes, dendritic cells (DCs), and vascular endothelium. Expression of CD40, CD54, and major histocompatibility complex (MHC) class II HLA-DR antigens by lesional keratinocytes was markedly reduced in serial biopsy specimens. Concurrent reductions in B7-1 (CD80), B7-2 (CD86), CD40, MHC class II, CD83, DC-lysosomal-associated membrane glycoprotein (DC-LAMP), and CD11c expression were detected on lesional DCs, which also decreased in number within lesional biopsies. Skin explant experiments suggested that these alterations in activated or mature DCs were not the result of direct toxicity of CTLA4Ig for DCs. Decreased lesional vascular ectasia and tortuosity were also observed and were accompanied by reduced presence of E-selectin, P-selectin, and CD54 on vascular endothelium. This study highlights the critical and proximal role of T cell activation through the B7-CD28/CD152 costimulatory pathway in maintaining the pathology of psoriasis, including the newly recognized accumulation of mature DCs in the epidermis.
The fear of volcano: short-term health effects after Mount Etna's eruption in 2002
Authors: V. Fano, A. Cernigliaro, S. Scondotto, C. A. Perucci, F. Forastiere
Journal: European Respiratory Journal (2010)

To the Editors:

The dramatic volcanic eruption in Iceland has recently brought the possible health effects of volcanic ashes to the general attention of the media. Lessons learnt from other episodes may be of interest and could guide future public health action.

During Autumn 2002, a large eruption of Mount Etna (Sicily, Italy) occurred. It persisted for 3 months, showing peaks of intense volcanic activity characterised by explosions, jets hundreds of metres high and seismic activity. Local winds carried the ash columns for kilometres, causing discomfort to the population of Catania (nearly 370,000 inhabitants) and other inhabited areas near the volcano. Repeated episodes of rainfall occurred after the eruption, reducing the phenomenon of ash resuspension. The population was alerted by a general alarm caused by national and local mass media. National and local authorities enacted measures aimed at preventing health effects: schools were closed; motor vehicle circulation was prohibited; protective eye masks were distributed; the elderly and individuals affected by chronic diseases of the respiratory system were suggested to limit their outdoor exposure and to reduce physical activity.

An epidemiologic study 1 on acute health effects on the nearby population was conducted. During the study period (106 days of observation in 2002; 59 days of eruption and 47 days of …
Circulating Osteocalcin Level Is Not Associated With Incident Type 2 Diabetes in Middle-Aged Male Subjects
Authors: You-Cheol Hwang, Jae-Hwan Jee, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung, Moon-Kyu Lee
Journal: Diabetes Care (2012)

OBJECTIVE Recent human studies suggested that serum osteocalcin is associated with the cross-talk between bone and energy metabolism. The aim of this study was to determine whether serum osteocalcin level is independently associated with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was performed of 1,229 nondiabetic men, aged 25–60 years, who were recruited from the Health Promotion Center, Samsung Medical Center, between January 1997 and December 1997. They were followed regularly at the center on an out-patient basis and during hospitalization for a mean of 8.4 years, and the development of type 2 diabetes was determined. RESULTS In the baseline analysis, BMI, body fat percentage, triglyceride, homeostasis model assessment of insulin resistance value, and plasminogen activator inhibitor-1 levels varied inversely with the osteocalcin tertiles, and serum high-density lipoprotein cholesterol levels increased with the osteocalcin tertiles. However, no differences were observed in fasting glucose and glycated hemoglobin levels across the osteocalcin tertiles. Incident type 2 diabetes occurred in 90 (7.3%) of the study subjects. In Cox proportional hazards models, however, no statistical differences in the development of type 2 diabetes across the osteocalcin tertiles were evident after adjustment of other risk factors for incident diabetes. CONCLUSIONS Despite baseline associations with favorable metabolic parameters, the serum osteocalcin level was not associated with the development of type 2 diabetes in middle-aged males.
Childhood and Adult Secondhand Smoke and Type 2 Diabetes in Women
Authors: Martin Lajous, Laura Tondeur, Guy Fagherazzi, Blandine de Lauzon-Guillain, Marie-Christine Boutron-Ruaualt, Françoise Clavel-Chapelon
Journal: Diabetes Care (2013)

OBJECTIVE The objective of this study was to evaluate the relationship between childhood and adult secondhand smoke and type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study among 37,343 French women from the E3N-EPIC (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale-European Prospective Investigation into Cancer and Nutrition) who never smoked and who were free of type 2 diabetes, cancer, or cardiovascular disease at baseline in 1992. Self-reported childhood secondhand smoke exposure was defined as having at least one parent who smoked. Adult secondhand smoke was defined as the sum of self-reported hours recorded at baseline of exposure to tobacco smoke from a spouse who smoked (or domestic close contact) and from outside the home. RESULTS Between 1992 and 2007, 795 cases of incident type 2 diabetes were identified and validated through a drug reimbursement dataset and a specific questionnaire. Women with at least one parent who smoked appeared to have an 18% higher rate of type 2 diabetes than women with parents who did not smoke (age-adjusted hazard ratio 1.18 [95% CI 1.02–1.36]). Adult secondhand smoke exposure (no exposure versus ≥4 h/day) was associated with an increased rate of type 2 diabetes (1.36 [1.05–1.77], P = 0.002 for trend) after adjusting for parental history of diabetes, education, body silhouette at age 8, childhood secondhand smoke exposure, physical activity, body mass index, hypertension, hypercholesterolemia, menopausal status and hormone use, alcohol intake, and processed red meat and coffee consumption. CONCLUSIONS This prospective analysis suggests that secondhand smoke exposure in childhood and adulthood are associated with a higher rate of type 2 diabetes.
Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance
Authors: E Spada, A Mele, A Berton, L Ruggeri, L Ferrigno, A R Garbuglia, M P Perrone, G Girelli, P Del Porto, E Piccolella, M U Mondelli, P Amoroso, R Cortese, A Nicosia, A Vitelli, A Folgori
Journal: Gut (2004)

<b>Background/Aims:</b> Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. <b>Methods:</b> The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. <b>Results:</b> Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. <b>Conclusion:</b> The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment.
Fractional Doses of Inactivated Poliovirus Vaccine in Oman
Authors: Ali Jafer Mohammed, Salah AlAwaidy, Shyam Bawikar, Padmamohan J. Kurup, Emadaldin Elamir, Mahmoud M.A. Shaban, Sharif M. Sharif, Harrie G.A.M. van der Avoort, Mark A. Pallansch, Pradeep Malankar, Anthony Burton, Meghana Sreevatsava, Roland W. Sutter
Journal: New England Journal of Medicine (2010)

We conducted a clinical trial of fractional doses of inactivated poliovirus vaccine administered to infants in Oman, in order to evaluate strategies for making the vaccine affordable for use in developing countries.We compared fractional doses of inactivated poliovirus vaccine (0.1 ml, representing one fifth of a full dose) given intradermally with the use of a needle-free jet injector device, with full doses of vaccine given intramuscularly, with respect to immunogenicity and reactogenicity. Infants were randomly assigned at birth to receive either a fractional dose or a full dose of inactivated poliovirus vaccine at 2, 4, and 6 months. We also administered a challenge dose of monovalent type 1 oral poliovirus vaccine at 7 months and collected stool samples before and 7 days after administration of the challenge dose.A total of 400 infants were randomized, of whom 373 (93.2%) fulfilled the study requirements. No significant baseline differences between the groups were detected. Thirty days after completion of the three-dose schedule, the rates of seroconversion to types 1, 2, and 3 poliovirus were 97.3%, 95.7%, and 97.9%, respectively, in the fractional-dose group, as compared with 100% seroconversion to all serotypes in the full-dose group (P=0.01 for the comparison with respect to type 2 poliovirus; results with respect to types 1 and 3 poliovirus were not significant). The median titers were significantly lower in the fractional-dose group than in the full-dose group (P<0.001 for all three poliovirus serotypes). At 7 months, 74.8% of the infants in the fractional-dose group and 63.1% of those in full-dose group excreted type 1 poliovirus (P=0.03). Between birth and 7 months, 42 hospitalizations were reported, all related to infectious causes, anemia, or falls, with no significant difference between vaccination groups.These data show that fractional doses of inactivated poliovirus vaccine administered intradermally at 2, 4, and 6 months, as compared with full doses of inactivated poliovirus vaccine given intramuscularly on the same schedule, induce similar levels of seroconversion but significantly lower titers. (Current Controlled Trials number, ISRCTN17418767.)
Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery
Authors: B. Bermudez, S. Lopez, Y. M. Pacheco, J. Villar, F. J.G. Muriana, J. D. Hoheisel, A. Bauer, R. Abia
Journal: Cardiovascular Research (2008)

Postprandial triglyceride-rich lipoproteins (TRL) have a direct effect on vascular smooth muscle cells (SMC) and they increase the risk of atherogenesis. Here, we have tested the hypothesis that the different fatty acid composition of TRL is capable of differentially modifying gene expression in human coronary artery SMC (CASMC). In addition, the effect of TRL on cell proliferation and transcription factor activation was also evaluated.TRL were prepared from plasma of healthy volunteers after the ingestion of meals enriched in refined olive oil (ROO), butter or a mixture of vegetable and fish oils (VEFO). We use cDNA microarrays to determine the genes differentially expressed in TRL-treated CASMC. Correspondence cluster analysis demonstrated that TRL-butter, -ROO and -VEFO provoked different transcriptional profiles in CASMC. Sixty-six genes were regulated by TRL-butter, 55 by -ROO, and 47 by -VEFO. The data revealed that TRL-butter predominantly activated genes involved in the regulation of cell proliferation and inflammation. Likewise, TRL-VEFO induced the expression of genes implicated in inflammation, while TRL-ROO promoted a less atherogenic gene profile.The pathophysiological contribution of TRL to the development of atherosclerosis and the stability of atherosclerotic plaques may depend on the fatty acid composition of TRL. Our findings suggest a role for macrophage-inhibiting cytokine-1 (MIC-1) in coronary artery cardiovascular events.
Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors.
Authors: T S Ravikumar, G Pizzorno, W Bodden, J Marsh, R Strair, J Pollack, R Hendler, J Hanna, E D'Andrea
Journal: Journal of Clinical Oncology (1994)

PURPOSE This prospective, nonrandomized trial evaluated a percutaneous isolated chemotherapy perfusion approach for treating advanced primary and metastatic liver tumors. Chemotherapy was administered via hepatic artery catheter and hepatic venous blood isolated by a novel percutaneous double-balloon inferior vena cava (IVC) catheter was passed through a detoxification/filtration cartridge in a venovenous bypass circuit. PATIENTS AND METHODS Among 23 patients enrolled onto the study, 58 procedures were performed on 21 patients. Twelve patients received dose escalations of fluorouracil (5-FU) (1,000 mg/m2 to 5,000 mg/m2), and nine received dose escalations of doxorubicin (50 mg/m2 to 120 mg/m2). Pharmacokinetic studies included drug accumulation in the liver, extraction by detoxification filters, systemic exposure, and alterations of half-life. Each patient received two treatments at 3-week intervals. Those showing stabilization or response received additional treatments. RESULTS There was a direct relationship between dose and peak concentration of drug entering the hepatic veins. The system functioned efficiently throughout the dose range, with extraction efficiencies ranging from 64% to 91% (P &lt; .001). The hepatic vein drug levels showed a sixfold increase in 5-FU with dose escalation from 1,000 to 5,000 mg/m2, and a twofold increase in dox with dose escalation from 50 to 120 mg/m2 (P &lt; .001, filter-mediated drug extraction). The treatments were accomplished with only an overnight hospital stay and no mortality. The common procedure-related toxicity was transient hypotension (grade I to II), due to catecholamine depletion by the filter. Dose-limiting toxicity (leukopenia) was observed in patients receiving 5-FU at a dose of 5,000 mg/m2 and doxorubicin at a dose of 120 mg/m2. Significant tumor response (&gt; 95% reduction) was obtained in two patients receiving doxorubicin at 90 mg/m2 and 120 mg/m2. CONCLUSION The use of a double-balloon catheter to isolate and detoxify hepatic venous blood during intraarterial therapy is technically feasible, safe, and allows administration of large doses of intrahepatic chemotherapy at short intervals. This approach should allow new dose-intensification strategies to increase tumor responses in primary and metastatic liver tumors.
Re: β-Carotene: a Miss for Epidemiology
Authors: Matthew Brignall, Davis Lamson
Journal: JNCI Journal of the National Cancer Institute (2000)

In an editorial in the December 15 issue of the Journal, Dr. James Marshall presents a compelling hypothesis about the apparent disagreement between the epidemiologic and experimental data regarding b-carotene as a chemopreventative agent (1). He argues that b-carotene may have been only a marker compound for one or more other protective phytonutrients. Indeed, there are ample data to support such reasoning. However, there is another equally compelling reason for the disparate findings on b-carotene. The synthetic form of b-carotene found in supplements, and hence used in most clinical trials, is the all-trans form. The naturally occurring form of this nutrient contains about 50% trans-isomer and several other forms, the most prevalent being 9-cis-b-carotene (2,3). While serum concentrations of the highly lipophilic 9-cis isomer are very low, even with supplementation of natural, mixed isomeric carotenoids (2), tissue concentrations of this compound have been measured at 10%–20% of total b-carotene (4). The 9-cis form of b-carotene has much greater antioxidant activity in humans than the synthetic all-trans form (2). Moreover, in vitro (5) and preliminary human data (3) indicate that the naturally occurring forms of b-carotene have a better ability to block malignant transformation than the synthetic alltrans isomer. Animal studies (6,7) suggest that the preferred form of carotenes for future studies should be the palm carotenoids, which contain lycopene, lutein, and a-carotene, in addition to the mixed isomers of b-carotene. In summary, Dr. Marshall’s assertion that further investigation of the antimalignant transformation activity of synthetic b-carotene supplements is not justified seems to be accurate. However, before we dismiss carotenes altogether, we should investigate the effect of palm carotenes in large-scale human trials.
Antitumor activity of the combination of synthetic retinoid ST1926 and cisplatin in ovarian carcinoma models
Authors: C. Pisano, L. Vesci, R. Foderà, F.F. Ferrara, C. Rossi, M. De Cesare, V. Zuco, G. Pratesi, R. Supino, F. Zunino
Journal: Annals of Oncology (2007)
Predictors of Postoperative Quality of Life After Esophagectomy for Cancer
Authors: Therese Djärv, Jane M. Blazeby, Pernilla Lagergren
Journal: Journal of Clinical Oncology (2009)

To identify factors predictive of health-related quality of life (HRQL) 6 months after surgery for esophageal cancer.A Swedish nationwide population-based study of patients undergoing esophagectomy for cancer was undertaken between 2001 and 2005. Clinical details (sex, age, body mass index [BMI], comorbidity) and tumor details (histology, stage, and location) were prospectively recorded and validated. HRQL questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and OES18) were used to assess HRQL 6 months postoperatively. HRQL outcome was categorized as good or poor by collapsing the four response categories. Logistic regression models adjusting for potential confounding factors were used to assess the association between preoperative patient and tumor characteristics and HRQL outcome 6 months after surgery.A total of 355 patients (77% of eligible) responded to the HRQL questionnaires. Age, sex, and BMI showed no associations with HRQL 6 months after surgery, but patients with comorbidity, a more advanced tumor stage (III to IV), or a tumor located in the middle or upper esophagus had an increased risk of poor HRQL. Patients with adenocarcinoma had a lower risk of poor HRQL than patients with squamous cell carcinoma.Knowledge of risk factors for poor postoperative HRQL may be relevant for clinical decision making. More research to see whether these factors are further predictive of poor HRQL in long-term survivors is needed.
The Subplate, A Transient Neocortical Structure: Its Role in the Development of Connections between Thalamus and Cortex
Authors: K L Allendoerfer, C J Shatz
Journal: Annual Review of Neuroscience (1994)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Non-coding RNAs in the pathogenesis of COPD
Authors: Elise G De Smet, Pieter Mestdagh, Jo Vandesompele, Guy G Brusselle, Ken R Bracke
Journal: Thorax (2015)

A large part of the human genome is transcribed in non-coding RNAs, transcripts that do not code for protein, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). MiRNAs are short single-stranded RNA molecules that negatively regulate gene expression at the post-transcriptional level. They play an important regulatory role in many biological processes. Consequently, altered expression of these non-coding RNAs has been shown to lead to inflammation and disease. In contrast, lncRNAs, can both enhance or repress the expression of protein-coding genes. COPD is typically caused by tobacco smoking and leads to a progressive decline in lung function and a premature death. Exaggerated pulmonary inflammation is a hallmark feature in this disease, leading to obstructive bronchiolitis and emphysema. In this review, we discuss the miRNA expression patterns in lungs of patients with COPD and in mouse models and we highlight various miRNAs involved in COPD pathogenesis. In addition, we briefly discuss a specific lncRNA that is upregulated upon cigarette smoke exposure, providing a short introduction to this more recently discovered group of non-coding RNAs.
Effects of atrial natriuretic factor on cyclic guanosine monophosphate and cyclic adenosine monophosphate accumulation in microdissected nephron segments from rats.
Authors: H Nonoguchi, M A Knepper, V C Manganiello
Journal: Journal of Clinical Investigation (1987)

Atrial natriuretic factor (ANF) (1 microM) markedly increased cyclic guanosine monophosphate (cGMP) content in microdissected glomeruli (35-fold) and in microdissected inner medullary collecting ducts (IMCD) (20-fold). ANF caused little or no increase in cGMP content in other nephron segments. The threshold concentration for increased cGMP accumulation by ANF was 0.1-1 nM in IMCD, which is in the range reported for rat plasma. Sodium nitroprusside (1 mM), which selectively stimulates soluble guanylate cyclase, increased cGMP content in glomeruli but not in IMCD. ANF did not alter cAMP accumulation in the absence or presence of vasopressin (AVP) or parathyroid hormone (PTH) in outer and inner medullary tubule suspensions, or in microdissected proximal convoluted tubules (PCT), medullary thick ascending limbs (MAL) or IMCD. These data are compatible with the hypothesis that cGMP is a second messenger for a physiologic action of ANF in the inner medullary collecting duct. ANF apparently activates membrane-bound guanylate cyclase in this segment.