tbuckley/cabot-search huggingface dataset:
Immune response in the mutant diabetic C57BL/Ks-dt+ mouse. Discrepancies between in vitro and in vivo immunological assays.
Authors: G Fernandes, B S Handwerger, E J Yunis, D M Brown
Journal: Journal of Clinical Investigation (1978)

Cell-mediated and humoral immune responses of mutant diabetic db+/db+ mice were evaluated using in vivo and in vitro immunological assays. When compared to lean, nondiabetic db+/m+ or m+/m+ mice, db+/db+ mice demonstrated markedly altered in vivo immune responses characterized by a significantly diminished ability to reject allogeneic skin grafts, a markedly diminished capacity to generate cytotoxic cells after sensitization with allogeneic EL-4 lymphoma cells and a significantly enhanced plaque-forming cell response to sheep erythrocytes. In contrast, spleen cells from db+/db+ mice demonstrated only minimal alterations in in vitro responses to mitogens and allogeneic cells and no alteration in their capacity to generate an in vitro plaque-forming cell response. The spleens and thymuses of db+/db+ mice weighed significantly less than organs from db+/db+ mice. In addition, thymuses from db+/db+ mice demonstrated a marked deficiency in in vivo [125I]UdR uptake. These data suggest that the altered metabolic status of the diabetic host influences immune function in vivo possibly due to abnormal function of lymphocyte subpopulations.
Food Consumption by Individuals in the United States: Two Major Surveys
Authors: Patricia B. Swan
Journal: Annual Review of Nutrition (1983)

INTRODUCTION.. . . . ... .. .. . . . . . ... ... . .. . . . . . .. .. .. . . .. . . . .... ... . . . . . . . . . .. .. . . . . . . . . . . . . . . . . . . . . . 413 HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414 DESIGN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415 RESULTS FROM NHANES AND NFCS  416 USEFULNESS OF NFCS AND NHANES RESULTS  422 CONCLUSIONS . . . .. . . . . . . ... . . . . . . . . . . . . . .... . .. . . . . .. . .. . . . . . . . . ... . ... . . . . . ... . .. . .   426
IDO Expression in Brain Tumors Increases the Recruitment of Regulatory T Cells and Negatively Impacts Survival
Authors: Derek A. Wainwright, Irina V. Balyasnikova, Alan L. Chang, Atique U. Ahmed, Kyung-Sub Moon, Brenda Auffinger, Alex L. Tobias, Yu Han, Maciej S. Lesniak
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Glioblastoma multiforme (GBM) is an aggressive adult brain tumor with a poor prognosis. One hallmark of GBM is the accumulation of immunosuppressive and tumor-promoting CD4+FoxP3+GITR+ regulatory T cells (Tregs). Here, we investigated the role of indoleamine 2,3 dioxygenase (IDO) in brain tumors and the impact on Treg recruitment. Experimental Design: To determine the clinical relevance of IDO expression in brain tumors, we first correlated patient survival to the level of IDO expression from resected glioma specimens. We also used novel orthotopic and transgenic models of glioma to study how IDO affects Tregs. The impact of tumor-derived and peripheral IDO expression on Treg recruitment, GITR expression, and long-term survival was determined. Results: Downregulated IDO expression in glioma predicted a significantly better prognosis in patients. Coincidently, both IDO-competent and deficient mice showed a survival advantage bearing IDO-deficient brain tumors, when compared with IDO-competent brain tumors. Moreover, IDO deficiency was associated with a significant decrease in brain-resident Tregs, both in orthotopic and transgenic mouse glioma models. IDO deficiency was also associated with lower GITR expression levels on Tregs. Interestingly, the long-term survival advantage conferred by IDO deficiency was lost in T-cell–deficient mice. Conclusions: These clinical and preclinical data confirm that IDO expression increases the recruitment of immunosuppressive Tregs that lead to tumor outgrowth. In contrast, IDO deficiency decreases Treg recruitment and enhances T-cell–mediated tumor rejection. Thus, the data suggest a critical role for IDO-mediated immunosuppression in glioma and support the continued investigation of IDO–Treg interactions in the context of brain tumors. Clin Cancer Res; 18(22); 6110–21. ©2012 AACR.
The obstructive subaortic conus.
Authors: J D Waldman, A Schneeweiss, W D Edwards, J J Lamberti, A Shem-Tov, H N Neufeld
Journal: Circulation (1984)

Eleven children are reported who had stenosis under a malposed aorta with gradients of 20 to 76 mm Hg between the right ventricle and aorta. The subaortic obstruction was caused by hypertrophy of the foreshortened infundibulum and malalignment of the infundibular septum relative to the remainder of the ventricular septum. Of these 11 patients, nine had a ventricular septal defect and seven had coarctation of the aorta. Rightward deviation of the infundibulum and aorta produced an unusually long left main coronary artery that was compressed by the stent of a bioprosthetic conduit valve in one patient. Serial cardiac catheterization studies in four patients showed progressive stenosis in each. Subaortic stenosis can develop in patients with malposition of the aorta and the frequency may be greater than 5% since milder forms are likely to occur. The obstruction can be progressive. The left coronary artery may be particularly vulnerable to compression after operative repair with an extracardiac conduit.
Performance of fiberbronchoscopy in patients with neoplasia endoscopic findings
Authors: Nuria Maria Reina Marfil, Rafael Garcia Montesinos, Ezequiel Ortega Sáenz de Tejada, Concepción Mena Escobar, Lidia López López, María Victoria Hidalgo Sanjuán
Journal: European Respiratory Journal (2012)

OBJECTIVE: Knowing the profitability of fiberbronschoscopy (FB) and the samples taken in patients with endoscopic findings of neoplasia. METHODS: During 63 months (october/06-december/11), we performed 642 FB with signs of neoplasia. We repeated 34 FB, so the final number of FB analized was 676. Mediastinal masses were excluded. We considered a) direct signs of neoplasia (DSN) when there was endobronchial mass or mucose infiltration, and b) indirect signs of neoplasia (ISN), when there was extrinsic compression of the bronchial wall or very hyperemic mucosa areas. According to endoscopic findings, bronchial biopsy, brushing and blind transbronchial needle aspiration (TBNA) of linfadenopathies were carried out. We always took a sample of bronchial secretion and if it was possible, a postFB sputum. We considered as positive samples which allowed to make a therapeutic decision, and negative samples those reported as “carcinoma” without specifying the type and presence of “malignant” or “atypical” cells. RESULTS: From this 676 FB, DSN were found in 439 (65%) patients and ISN in 237 (35%). There were 588 (86.9%) diagnostic FB, 410 (93.3%) of those with DSN and 178 (75.1%) with ISN.  CONCLUSIONS: 1) The FB profitability is within the reference values mentioned in the bibliography and we consider a good result in the patients with DSN. 2) The biopsy has been the most profitable sample although very similar to brushing and TBNA of linfadenopathies.
Neutrophil activation in fibrosing alveolitis: a comparison of lone cryptogenic fibrosing alveolitis and systemic sclerosis
Authors: JB Cailes, C O'Connor, P Pantelidis, AM Southcott, MX Fitzgerald, CM Black, RM du Bois
Journal: European Respiratory Journal (1996)

Fibrosing alveolitis complicating systemic sclerosis (FASSc) carries a better prognosis than lone cryptogenic fibrosing alveolitis (CFA). We wanted to determine whether this improved prognosis is associated with differential neutrophil migration and activation in the lower respiratory tract. We therefore compared bronchoalveolar lavage (BAL) neutrophil numbers and levels of neutrophil-derived enzymes in FASSc, CFA and normal individuals. Bronchoalveolar lavage was performed on 45 subjects (FASSc n = 20; CFA n = 15; normals n = 10); cell counts and levels of neutrophil-derived enzymes, myeloperoxidase, elastase (total elastase and elastase/alpha 1 antitrypsin complexes), collagenase and lactoferrin were measured. Lung function testing was performed in subjects with fibrosing alveolitis. Significant differences in the levels of collagenase, myeloperoxidase and elastase/ alpha 1-antitrypsin complexes were present in the BAL fluid from the three groups. Patients with CFA had significantly higher neutrophil percentages and levels of collagenase and myeloperoxidase than those with FASSc. Disease extent, as judged by lung volumes and gas transfer, was comparable in the CFA and FASSc groups. Forced vital capacity (% predicted) was significantly lower in patients with evidence of increased neutrophil enzyme release than those without. We conclude that: 1) increased neutrophil migration to the lung is accompanied by release both of primary and secondary granule enzymes in cryptogenic fibrosing alveolitis; and 2) the lower amounts of neutrophil products in fibrosing alveolitis complicating systemic sclerosis may account for the improved prognosis, even when disease is as extensive as in cryptogenic fibrosing alveolitis.
Dantrolene Enhances Antisense-Mediated Exon Skipping in Human and Mouse Models of Duchenne Muscular Dystrophy
Authors: Genevieve C. Kendall, Ekaterina I. Mokhonova, Miriana Moran, Natalia E. Sejbuk, Derek W. Wang, Oscar Silva, Richard T. Wang, Leonel Martinez, Qi L. Lu, Robert Damoiseaux, Melissa J. Spencer, Stanley F. Nelson, M. Carrie Miceli
Journal: Science Translational Medicine (2012)

Duchenne muscular dystrophy (DMD) causes profound and progressive muscle weakness and loss, resulting in early death. DMD is usually caused by frameshifting deletions in the gene DMD, which leads to absence of dystrophin protein. Dystrophin binds to F-actin and components of the dystrophin-associated glycoprotein complex and protects the sarcolemma from contraction-induced injury. Antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach aimed at restoring the DMD reading frame and allowing expression of an intact dystrophin glycoprotein complex. To date, low levels of dystrophin protein have been produced in humans by this method. We performed a small-molecule screen to identify existing drugs that enhance antisense-directed exon skipping. We found that dantrolene, currently used to treat malignant hyperthermia, potentiates antisense oligomer-guided exon skipping to increase exon skipping to restore the mRNA reading frame, the sarcolemmal dystrophin protein, and the dystrophin glycoprotein complex in skeletal muscles of mdx mice when delivered intramuscularly or intravenously. Further, dantrolene synergized with multiple weekly injections of antisense to increase muscle strength and reduce serum creatine kinase in mdx mice. Dantrolene similarly promoted antisense-mediated exon skipping in reprogrammed myotubes from DMD patients. Ryanodine and Rycal S107, which, like dantrolene, targets the ryanodine receptor, also promoted antisense-driven exon skipping, implicating the ryanodine receptor as the critical molecular target.
Alteration of clonal profile. I. Effect of sublethal irradiation on the responses to phosphorylcholine in BALB/c mice.
Authors: D R Kaplan, J Quintáns
Journal: The Journal of Experimental Medicine (1978)

BALB/c mice exhibit greater than 90% H8 clonal dominance in the immune response to phosphorylcholine. Adult mice exposed to 500 rads were initally unable to produce a humoral immune response to both phosphorylcholine and trinitrophenol antigens, and the direct plaque-forming cell response was slowly regained over several weeks. Clonotypic analysis wity antisera directed against the H8 idiotype showed that the H8 clone initially dominated the recovery of the response to phosphorycholine but that 60 days after the irradiation significant numbers of non-H8 clones could be detected. This same pattern could be seen in mice irradiated with 100 rads, a dose that does not completely abrogate the H8 response to phosphorylcholine. Sublethal irradiation of neonates before they had acquired responsiveness to phosphorylcholine could also eventually lead to the emergence of non-H8 idiotypes. Thus, a radiosensitive element regulates the expression of clonal dominance in anti-phosphorylcholine responses of BALB/c mice.
Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles
Authors: Edward J. Chisholm, Georges Vassaux, Pilar Martin-Duque, Raphael Chevre, Olivier Lambert, Bruno Pitard, Andrew Merron, Mark Weeks, Jerome Burnet, Inge Peerlinck, Ming-Shen Dai, Ghassan Alusi, Stephen J. Mather, Katherine Bolton, Ijeoma F. Uchegbu, Andreas G. Schatzlein, Patrick Baril
Journal: Cancer Research (2009)

Abstract The lack of safe and efficient systemic gene delivery vectors has largely reduced the potential of gene therapy in the clinic. Previously, we have reported that polypropylenimine dendrimer PPIG3/DNA nanoparticles are capable of tumor transfection upon systemic administration in tumor-bearing mice. To be safely applicable in the clinic, it is crucial to investigate the colloidal stability of nanoparticles and to monitor the exact biodistribution of gene transfer in the whole body of the live subject. Our biophysical characterization shows that dendrimers, when complexed with DNA, are capable of forming spontaneously in solution a supramolecular assembly that possesses all the features required to diffuse in experimental tumors through the enhanced permeability and retention effect. We show that these nanoparticles are of sizes ranging from 33 to 286 nm depending on the DNA concentration, with a colloidal stable and well-organized fingerprint-like structure in which DNA molecules are condensed with an even periodicity of 2.8 nm. Whole-body nuclear imaging using small-animal nano-single-photon emission computed tomography/computer tomography scanner and the human Na/I symporter (NIS) as reporter gene shows unique and highly specific tumor targeting with no detection of gene transfer in any of the other tissues of tumor-bearing mice. Tumor-selective transgene expression was confirmed by quantitative reverse transcription-PCR at autopsy of scanned animals, whereas genomic PCR showed that the tumor sites are the predominant sites of nanoparticle accumulation. Considering that NIS imaging of transgene expression has been recently validated in humans, our data highlight the potential of these nanoparticles as a new formulation for cancer gene therapy. [Cancer Res 2009;69(6):2655–62]
Safety assessment of enzyme-containing personal cleansing products: Exposure characterization and development of IgE antibody to enzymes after a 6-month use test☆☆☆★★★
Authors: Christopher K. Kelling, Robert G. Bartolo, Keith D. Ertel, Laurence A. Smith, Debra D. Watson, Katherine Sarlo
Journal: Journal of Allergy and Clinical Immunology (1998)
Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice
Authors: Madhukar H. Trivedi, A. John Rush, Stephen R. Wisniewski, Andrew A. Nierenberg, Diane Warden, Louise Ritz, Grayson Norquist, Robert H. Howland, Barry Lebowitz, Patrick J. McGrath, Kathy Shores-Wilson, Melanie M. Biggs, G. K. Balasubramani, Maurizio Fava
Journal: American Journal of Psychiatry (2006)

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, but the rates, timing, and baseline predictors of remission in "real world" patients are not established. The authors' primary objectives in this study were to evaluate the effectiveness of citalopram, an SSRI, using measurement-based care in actual practice, and to identify predictors of symptom remission in outpatients with major depressive disorder.This clinical study included outpatients with major depressive disorder who were treated in 23 psychiatric and 18 primary care "real world" settings. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks. The clinicians were assisted by a clinical research coordinator in the application of measurement-based care, which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures. Remission was defined as an exit score of <or=7 on the 17-item Hamilton Depression Rating Scale (HAM-D) (primary outcome) or a score of <or=5 on the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) (secondary outcome). Response was defined as a reduction of >or=50% in baseline QIDS-SR score.Nearly 80% of the 2,876 outpatients in the analyzed sample had chronic or recurrent major depression; most also had a number of comorbid general medical and psychiatric conditions. The mean exit citalopram dose was 41.8 mg/day. Remission rates were 28% (HAM-D) and 33% (QIDS-SR). The response rate was 47% (QIDS-SR). Patients in primary and psychiatric care settings did not differ in remission or response rates. A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment. Participants who were Caucasian, female, employed, or had higher levels of education or income had higher HAM-D remission rates; longer index episodes, more concurrent psychiatric disorders (especially anxiety disorders or drug abuse), more general medical disorders, and lower baseline function and quality of life were associated with lower HAM-D remission rates.The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials. The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results.
Prediction of Coronary Heart Disease Risk in a General, Pre-Diabetic, and Diabetic Population During 10 Years of Follow-up: Accuracy of the Framingham, SCORE, and UKPDS Risk Functions
Authors: Amber A.W.A. van der Heijden, Monica M. Ortegon, Louis W. Niessen, Giel Nijpels, Jacqueline M. Dekker
Journal: Diabetes Care (2009)

To test the validity of the Framingham, Systematic Coronary Risk Evaluation (SCORE), and UK Prospective Diabetes Study (UKPDS) risk function in the prediction of risk of coronary heart disease (CHD) in populations with normal glucose tolerance (NGT), intermediate hyperglycemia, and type 2 diabetes.Calibration and discrimination of the three prediction models were tested using prospective data for 1,482 Caucasian men and women, 50-75 years of age, who participated in the Hoorn Study. All analyses were stratified by glucose status.During 10 years of follow-up, a total of 197 CHD events, of which 43 were fatal, were observed in this population, with the highest percentage of first CHD events in the diabetic group. The Framingham and UKPDS prediction models overestimated the risk of first CHD event in all glucose tolerance groups. Overall, the prediction models had a low to moderate discriminatory capacity. The SCORE risk function was the best predictor of fatal CHD events in the group with NGT (area under the receiver operating characteristic curve 0.79 [95% CI 0.70-0.87]), whereas the UKPDS performed better in the intermediate hyperglycemia group (0.84 [0.74-0.94]) in the estimation of fatal CHD risk. After exclusion of known diabetic patients, all prediction models had a higher discriminatory ability in the group with diabetes.The use of the Framingham function for prediction of the first CHD event is likely to overestimate an individual's absolute CHD risk. In CHD prevention, application of the SCORE and UKPDS functions might be useful in the absence of a more valid tool.
Clinical Findings with Implications for Genetic Testing in Families with Clustering of Colorectal Cancer
Authors: Juul T. Wijnen, Hans F.A. Vasen, P. Meera Khan, Aeilko H. Zwinderman, Heleen van der Klift, Adri Mulder, Carli Tops, Pål Møller, Riccardo Fodde, Fred Menko, Babs Taal, Fokko Nagengast, Han Brunner, Jan Kleibeuker, Rolf Sijmons, Gerrit Griffioen, Annette Bröcker-Vriends, Egbert Bakker, Inge van Leeuwen-Cornelisse, Anne Meijers-Heijboer, Dick Lindhout, Martijn Breuning, Jan Post, Cees Schaap, Jaran Apold, Ketil Heimdal, Lucio Bertario, Marie Luise Bisgaard, Petr Goetz
Journal: New England Journal of Medicine (1998)

Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PMS1, PMS2, and MSH6 ) cause susceptibility to hereditary nonpolyposis colorectal cancer. We assessed the prevalence of MSH2 and MLH1 mutations in families suspected of having hereditary nonpolyposis colorectal cancer and evaluated whether clinical findings can predict the outcome of genetic testing.
B-Myb, Cancer, Senescence, and MicroRNAs
Authors: Ivan Martinez, Daniel DiMaio
Journal: Cancer Research (2011)

The transcription factor B-Myb plays a critical role in regulating gene expression and is implicated in controlling carcinogenesis and cellular senescence. Transcription of the B-Myb gene is regulated by retinoblastoma proteins acting directly on the B-Myb promoter. Recently, we found that microRNAs also control the abundance of B-Myb mRNA during senescence, adding another level of complexity to B-Myb regulation. This review focuses on the importance of B-Myb in cancer and senescence, with an emphasis on the regulation of B-Myb expression and activity.
P33 Iron deficiency independently predicts survival in idiopathic pulmonary arterial hypertension
Authors: C. Rhodes, L. Howard, M. Busbridge, D. Ashby, E. Kondili, J. Gibbs, J. Wharton, M. Wilkins
Journal: Thorax (2010)

<h3>Objectives</h3> Characterise the iron status of patients with idiopathic pulmonary arterial hypertension (IPAH) and its clinical importance. <h3>Methods</h3> Circulating markers of iron status and erythropoiesis were determined in 135 patients with IPAH and correlated with clinical indices and survival. <h3>Results</h3> Iron deficiency, defined by raised plasma soluble transferrin receptor (sTfR) levels (&gt;28.1 nmol/l) was present in ∼63% of patients with IPAH. Iron, ferritin and transferrin saturation levels were also reduced (Abstract P33 Figure 1); whereas mean haematocrit and haemoglobin levels were similar to healthy controls and red cell distribution width was increased. Levels of the master iron regulator hepcidin, which inhibits the dietary uptake and decreases serum iron, were raised (50.5 vs 34.4±3.0 ng/ml; p=0.04) despite the presence of iron deficiency in the majority of patients. Hepcidin correlated inversely with sTfR and erythropoietin (EPO) levels as would be expected, but not with IL-6, the most important inflammatory stimulus for hepcidin expression. After adjusting for iron status, hepcidin levels were significantly higher in IPAH compared with healthy controls (p=0.001). Plasma sTfR levels increased with WHO class (p&lt;0.05), showed a weak but significant correlation with 6MWD (R=−0.25, p=0.03) and growth differentiation factor-15 (R=0.281, p=0.01) and independently predicted survival after adjustments for 6MWD, WHO class and NT pro-BNP levels (p=0.022). <h3>Conclusions</h3> A significant proportion of IPAH patients are iron deficient and this relates to disease severity and outcome. Hepcidin levels are inappropriately high in IPAH and may be driving iron deficiency.