tbuckley/cabot-search huggingface dataset:
Randomized Phase II Trial of Chemoradiotherapy Followed by Either Dose-Dense or Metronomic Temozolomide for Newly Diagnosed Glioblastoma
Authors: Jennifer L. Clarke, Fabio M. Iwamoto, Joohee Sul, Katherine Panageas, Andrew B. Lassman, Lisa M. DeAngelis, Adília Hormigo, Craig P. Nolan, Igor Gavrilovic, Sasan Karimi, Lauren E. Abrey
Journal: Journal of Clinical Oncology (2009)

Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma (GBM) by increasing the therapeutic index, overcoming common mechanisms of temozolomide resistance, or both. The goal of this randomized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM.Adult patients with newly diagnosed GBM were randomly assigned to receive standard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense (150 mg/m(2) days 1 to 7 and 15 to 21) or metronomic (50 mg/m(2) continuous daily) temozolomide. Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression. The primary end point was overall survival (OS) at 1 year. Tumor tissue was assayed to determine O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.Eighty-five eligible patients were enrolled; 42 were randomly assigned to dose-dense and 43 to metronomic temozolomide. The 1-year survival rate was 80% for the dose-dense arm and 69% for the metronomic arm; median OS was 17.1 months (95% CI, 14.0 to 28.1 months) and 15.1 months (95% CI, 12.3 to 18.9 months), respectively. The most common toxicities were myelosuppression (leukopenia, neutropenia, and thrombocytopenia) and elevated liver enzymes. Pseudoprogression was observed in 37% of assessable patients and may have had an impact on estimates of progression-free survival (6.6 months in the dose-dense arm and 5.0 months in the metronomic arm).Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity. The dose-dense regimen appears promising, with 1-year survival of 80%.
Vocational Adjustment and General Well-Being of Young Adults With IDDM
Authors: Cameron K Tebbi, Clifford Bromberg, Irene Sills, Jack Cukierman, Marion Piedmonte
Journal: Diabetes Care (1990)

The vocational experiences and general well-being of 58 young adult subjects (mean age 24.3 yr) with insulindependent diabetes mellitus (IDDM) diagnosed during their adolescence were compared with that of 55 healthy matched control subjects with linear logistic discriminant function analyses. Assessment measures included the Rand General Well-Being Scale and the Rand Functional Limitations and Physical Abilities Batteries. Diabetic subjects, on average, reported significantly lower general well-being than control subjects, particularly in terms of health-related fears and feelings of depression. However, diabetic subjects did not report a pervasive functional deficit relative to control subjects and experienced similar employment rates and problems in the workplace. These results suggest that this group of young adult diabetic subjects has adjusted well to the demands of the workplace despite lower reports of general well-being. The results are discussed in light of relevant sampling issues.
<i>TGFBI</i> Deficiency Predisposes Mice to Spontaneous Tumor Development
Authors: Ye Zhang, Gengyun Wen, Genze Shao, Cuidong Wang, Chyuansheng Lin, Hongbo Fang, Adayabalam S. Balajee, Govind Bhagat, Tom K. Hei, Yongliang Zhao
Journal: Cancer Research (2008)

Abstract Loss of TGFBI, a secreted protein induced by transforming growth factor-β, has been implicated in cell proliferation, tumor progression, and angiogenesis by in vitro studies. However, in vivo antitumor functions of TGFBI as well as the underlying molecular mechanism are not well understood. To these aims, we have generated a mouse model with disruption of TGFBI genomic locus. Mice lacking TGFBI show a retarded growth and are prone to spontaneous tumors and 7,12-dimethylbenz(a)anthracene–induced skin tumors. In relation to wild-type (WT) mouse embryonic fibroblasts (MEF), TGFBI−/− MEFs display increased frequencies of chromosomal aberration and micronuclei formation and exhibit an enhanced proliferation and early S-phase entry. Cyclin D1 is up-regulated in TGFBI−/− MEFs, which correlates with aberrant activation of transcription factor cyclic AMP–responsive element binding protein (CREB) identified by chromatin immunoprecipitation and luciferase reporter assays. TGFBI reconstitution in TGFBI−/− cells by either retroviral infection with WT TGFBI gene or supplement with recombinant mouse TGFBI protein in the culture medium leads to the suppression of CREB activation and cyclin D1 expression, and further inhibition of cell proliferation. Cyclin D1 up-regulation was also identified in most of the tumors arising from TGFBI−/− mice. Our studies provide the first evidence that TGFBI functions as a tumor suppressor in vivo. [Cancer Res 2009;69(1):37–44]
Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial
Authors: Jean-Pascal Machiels, Somasundaram Subramanian, Agnes Ruzsa, Gabor Repassy, Igor Lifirenko, Annika Flygare, Per Sørensen, Tina Nielsen, Steen Lisby, Paul MJ Clement
Journal: The Lancet Oncology (2011)
Association of chronic obstructive pulmonary disease and sleep apnea syndrome.
Authors: A Chaouat, E Weitzenblum, J Krieger, T Ifoundza, M Oswald, R Kessler
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The association of chronic obstructive pulmonary disease (COPD) and sleep apnea syndrome (SAS), which are both frequent diseases, is likely to occur in a number of patients. We have prospectively investigated a large series (n = 265) of patients who were selected solely on the basis of a confirmed diagnosis of SAS (apnea + hypopnea index > 20/hr). An obstructive spirographic pattern, defined by an FEV1/VC ratio < or = 60%, was observed in 30 of 265 patients (11%). These patients (subgroup "overlap") were older (58 +/- 9) versus 53 +/- 10 yr, p = 0.01) than the remainder of the study population, and all were male patients. Body mass index (BMI) was identical in overlap patients to that in the remainder. Vital capacity and FEV1 were lower, by definition, in the overlap group. PaO2 was lower (66 +/- 10 versus 74 +/- 10 mm Hg, p < 0.001) and PaCO2 higher (42 +/- 6 versus 38 +/- 4 mm Hg, p < 0.001) in the overlap group. Hypoxemia (Pao2, < or = 65 mm Hg) was observed in 17 of 30 overlap patients and in 54 of 235 of the remainder. Hypercapnia (Paco2 > or = 45 mm Hg) was observed in 8 of 30 overlap patients and in 19 of 235 of the remainder. The pulmonary artery mean pressure (PAP) was higher in overlap patients both at rest (20 +/- 6 versus 15 +/- 5 mm Hg, p < 0.01) and during steady-state exercise (37 +/- 12 versus 29 +/- 10 mm Hg, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Noninvasive Measurement of Nutrient Portal Blood Shunting: An Experimental Study with [14C]Ursodeoxyeholie Acid
Authors: Bernard Nordlinger, Michel Parquet, Recaredo Infante, Reginald Moreels, Pol Blondiau, Michele Boschat, Michèle Groussard, Claude Huguet
Journal: Hepatology (2007)

All of the methods proposed for measuring portal blood flow are either invasive, estimate total rather than nutrient flow, and none has proved reliable in cirrhotic patients. A method has been derived from pharmacokinetic principles used for the calculation of bioavailability of drugs according to the route of administration (i.v. or p.o.) and tested experimentally in 20 pigs. A tracer dose of [14C]ursodeoxycholic acid, a biliary acid with a high-liver first-pass effect, is administered in the duodenum, and serial peripheral blood samples are taken. Later, the same dose of the same drug is administered i.v. The shunt fraction of portal blood F is obtained by the ratio of the areas under the plasma level vs. time curves ("AUC") after p.o. and i.v. administrations: (see formula in text). The pigs were divided into three experimental groups. (i) Group I: undisturbed portal flow; (ii) Group II: total diversion of portal blood with an end-to-side portacaval shunt, and (iii) Group III: partial diversion of portal blood through a side-to-side portacaval shunt. Portal flow was measured during surgery with an electromagnetic flowmeter above and below the shunt and the degree of shunting calculated. Results show that the shunt fraction measured with ursodeoxycholic acid is well-correlated with hemodynamic data. No overlap between Groups I and III is observed. It is concluded that the shunt fraction of nutrient portal blood can be measured with this noninvasive method. Minute amounts of ursodeoxycholic acid were used in order to be completely metabolized by the liver, even in spite of hepatocellular dysfunction. Therefore, this method should be valid in cirrhotic patients and be useful to decide the type of portasystemic shunt to propose for the decompression of gastroesophageal varices.
Analysis of Lymphoid Cells Responding to Virus- and Tumor-Associated Antigens in Spleens of Syngeneic Mouse Mammary Tumor Systems With Low and High Oncogenic Potentials&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Diana M. Lopez, Ronald D. Paul
Journal: JNCI Journal of the National Cancer Institute (1982)

Nylon-nonadherent cells obtained from the spleens of tumor bearers of two BALB/c mouse colonies with different oncogenic potentials were found to be the lymphocyte subclass responsive in blastogenesis to their tumor-associated antigens (TAA), Thus Thy 1-positive spleen cells from BALB/cCrgl mice that received implants of a syngeneic, chemically induced mammary tumor and BALB/cfC3H mice bearing spontaneous mammary tumors (SMT) incorporated high levels of [3H]thymidine after in vitro exposure to homologous TAA preparations. These responses were evident in animals at the early stages of tumorigenesis but could not be detected in the T-cells of animals with large tumor burdens. Responses to murine mammary tumor virus (MuMTV) antigens were observed likewise in the nylonnonadherent spleen cell population of the MuMTV-positive BALB/cfC3H mice bearing small SMT. The responsiveness to viral antigens also decreased with progression of the disease, In BALB/cCrgl mice, which have a low incidence of SMT and are devoid of intact mouse mammary tumor virions, T-Iymphocytes appeared to be nonresponsive to MuMTV antigens, but nylon-adherent spleen lymphocytes were capable of being stimulated by MuMTV, The blastogenic response of these B-Iymphocytes was not altered by tumor initiation or progression. Depletion studies with the use of either anti-Thy 1 or antisurface immunoglobulin sera plus complement confirmed the validity of the results observed in the nylon wool column separation studies. Flow cytometric analyses of the spleen cells of tumor-bearing mice from both colonies revealed a depression of the levels of T-Iymphocytes with increasing tumor burden while there was no decrease in the percentage of B-cells. These results provided a possible explanation for the loss of blastogenic response to tumor antigens and to MuMTV observed in spleen cells of BALB/ctC3H mice with increasing tumor burden and for the unalterable responses to MuMTV that appeared in splenocytes of BALB/cCrgl mice at all stages of tumorigenesis.
A genome annotation-driven approach to cloning the human ORFeome.
Authors: John E Collins, Charmain L Wright, Carol A Edwards, Matthew P Davis, James A Grinham, Charlotte G Cole, Melanie E Goward, Begoña Aguado, Meera Mallya, Younes Mokrab, Elizabeth J Huckle, David M Beare, Ian Dunham
Journal: Genome biology (2004)

Abstract We have developed a systematic approach to generating cDNA clones containing full-length open reading frames (ORFs), exploiting knowledge of gene structure from genomic sequence. Each ORF was amplified by PCR from a pool of primary cDNAs, cloned and confirmed by sequencing. We obtained clones representing 70% of genes on human chromosome 22, whereas searching available cDNA clone collections found at best 48% from a single collection and 60% for all collections combined.
THE PATHOGENIC AGENT IN NORMAL HUMAN BONE MARROW: ITS NATURE AND RELATIONSHIP TO THE LYMPHADENOMA AGENT OF GORDON
Authors: U. Friedemann
Journal: BMJ (1934)

In a previous paper1 it was shown that when normal human bone marrow is injected intrathecally in rabbits these animals develop a progressive and fatal disturbance of the nervous system, paralysis of the hind legs being a characteristic feature of the late stages. It was recognized that the clinical appearances presented by these rabbits resembled those which M. H. ^Gordon2 had already found in rabbits injected intracerebrally with material* derived from human cases of lymphaden'oma, but the relationship of the two pathogenic agents was not more closely deter mined. The nature of the agent contained in normal human bone marrow?whether it is a living or a non living thing?was also left in doubt. The primary purpose of the present paper is to describe experiments directed towards the solution of these two problems. Right at the outset I must acknowledge deep indebted ness to Dr. Gordon. To his efforts and kindness I owe all the samples of human bone marrow and viscera used in the series of experiments to be described. I have called these human tissues normal? in the present paper. This is because I am satisfied they have represented the con ditions present in normal human beings. Actually the specimens have been obtained post mortem from a large variety of pathological conditions and from cases of accidental death.
Slow-Wave Activity Saturation and Thalamocortical Isolation During Propofol Anesthesia in Humans
Authors: Róisín Ní Mhuircheartaigh, Catherine Warnaby, Richard Rogers, Saad Jbabdi, Irene Tracey
Journal: Science Translational Medicine (2013)

The altered state of consciousness produced by general anesthetics is associated with a variety of changes in the brain's electrical activity. Under hyperpolarizing influences such as anesthetic drugs, cortical neurons oscillate at ~1 Hz, which is measurable as slow waves in the electroencephalogram (EEG). We have administered propofol anesthesia to 16 subjects and found that, after they had lost behavioral responsiveness (response to standard sensory stimuli), each individual's EEG slow-wave activity (SWA) rose to saturation and then remained constant despite increasing drug concentrations. We then simultaneously collected functional magnetic resonance imaging and EEG data in 12 of these subjects during propofol administration and sensory stimulation. During the transition to SWA saturation, the thalamocortical system became isolated from sensory stimuli, whereas internal thalamocortical exchange persisted. Rather, an alternative and more fundamental cortical network (which includes the precuneus) responded to all sensory stimulation. We conclude that SWA saturation is a potential individualized indicator of perception loss that could prove useful for monitoring depth of anesthesia and studying altered states of consciousness.
STAT5 Activation and Cardioprotection by Remote Ischemic Preconditioning in Humans
Authors: Gerd Heusch, Judith Musiolik, Eva Kottenberg, Jürgen Peters, Heinz Jakob, Matthias Thielmann
Journal: Circulation Research (2011)

The heart can be protected from infarction by brief episodes of ischemia/reperfusion of a remote organ. Remote ischemic preconditioning (RIPC) by brief arm ischemia/reperfusion has been recruited in patients undergoing coronary artery bypass surgery or percutaneous coronary interventions and during transport to the hospital for acute myocardial infarction. Cardioprotective signaling has been extensively characterized in animal experiments.To identify cardioprotective signaling by RIPC in humans.RIPC was induced by 3 cycles of 5 minutes of arm ischemia/5 minutes of reperfusion in patients undergoing coronary artery bypass surgery. Twelve patients each were randomly assigned to undergo RIPC or a sham control procedure. Protection was confirmed by reduced serum troponin I concentrations in patients with RIPC versus control patients. In myocardial biopsies, an array of established cardioprotective proteins was analyzed by Western immunoblotting. The phosphorylation of signal transducer and activator of transcription 5 (STAT5) increased from baseline before ischemic cardioplegic arrest to 10 minutes of reperfusion with RIPC, and STAT5 phosphorylation during reperfusion was greater in patients with RIPC than in control patients.The identification of this unique signaling signature of RIPC will facilitate the development of pharmacological cardioprotection.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01406678.
Adenoviral-Mediated, High-Level, Cell-Specific Transgene Expression: A SYN1-WPRE Cassette Mediates Increased Transgene Expression with No Loss of Neuron Specificity
Authors: Colin P.J. Glover, Alison S. Bienemann, Darren J. Heywood, A.Siobhan Cosgrave, James B. Uney
Journal: Molecular Therapy (2002)

Viral vectors are excellent tools for studying gene function in the brain, although a limitation has been the ability to effectively target transgene expression to specific neuronal populations. This generally cannot be overcome by the use of neuron-specific promoters, as most are too large to be used with current viral vectors and expression from these promoters is often relatively weak. We therefore developed a composite expression cassette, comprising 495 bp of the weak human SYN1 (synapsin-1) promoter and 800 bp of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Studies in hippocampal cultures, organotypic cultures, and in vivo showed that the 3′ addition of the WPRE to the SYN1 element greatly increased enhanced green fluorescent protein expression levels with no loss of neuronal specificity. In vivo studies also showed that transgene expression was enhanced with no loss of neuronal specificity in dentate-gyrus neurons for at least 6 weeks following transfection. Therefore, unlike most powerful promoter systems, which mediate expression in neurons and glia, this SYN1-WPRE cassette can target powerful long-term transgene expression to central nervous system neurons when delivered at relatively low titers of adenovirus. Its use should therefore facilitate both gene therapy studies and investigations of neuronal gene function. Viral vectors are excellent tools for studying gene function in the brain, although a limitation has been the ability to effectively target transgene expression to specific neuronal populations. This generally cannot be overcome by the use of neuron-specific promoters, as most are too large to be used with current viral vectors and expression from these promoters is often relatively weak. We therefore developed a composite expression cassette, comprising 495 bp of the weak human SYN1 (synapsin-1) promoter and 800 bp of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Studies in hippocampal cultures, organotypic cultures, and in vivo showed that the 3′ addition of the WPRE to the SYN1 element greatly increased enhanced green fluorescent protein expression levels with no loss of neuronal specificity. In vivo studies also showed that transgene expression was enhanced with no loss of neuronal specificity in dentate-gyrus neurons for at least 6 weeks following transfection. Therefore, unlike most powerful promoter systems, which mediate expression in neurons and glia, this SYN1-WPRE cassette can target powerful long-term transgene expression to central nervous system neurons when delivered at relatively low titers of adenovirus. Its use should therefore facilitate both gene therapy studies and investigations of neuronal gene function.
Phenotypic Characterization of the Eosinophilic Esophagitis (EoE) Population in the Consortium of Food Allergy Research (CoFAR)
Authors: Mirna Chehade, Stacie M. Jones, Robbie D. Pesek, A. Wesley Burks, Robert A. Wood, Donald Y.M. Leung, Robert W. Lindblad, Peter Dawson, J. Pablo Abonia, Joseph D. Sherrill, Hugh A. Sampson, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2015)

We sought to describe the clinical, endoscopic, and histopathological features of patients with EoE in a multi-site CoFAR registry. Subjects were 6 months-65 years with biopsy-confirmed EoE from 5 U.S. sites. Concurrent eosinophilia at other gastrointestinal sites was allowed. Resistance to proton pump inhibitor (PPI) therapy was recorded but not required. 506 subjects (71% males, 88% Caucasians, median age 10.5 [0.9-56] years) were enrolled. Median age was 3 years at symptom onset and 7 at diagnosis. 26% reported clinical and histological response to PPI therapy. 5.6% had concurrent eosinophilic gastritis, 0.6% enteritis, 2% colitis. Parents and siblings had reported EoE rates of 3.2% and 3.6%, respectively. Reported symptoms included abdominal pain (55%), reflux (53%), dysphagia (50%), nausea/vomiting (48%), and diarrhea (35%). Food impactions requiring endoscopic removal occurred in 5.9% and esophageal stricture in 10.7%. Esophageal rings/strictures were more common in older subjects (rings: 4.6% <16-year-olds, 21.9% ≥16-year-olds, p=0.01; strictures: 3% <16-year-olds, 17.9% ≥16-year-olds, p=0.03). Plaques/furrows and esophageal eosinophils were comparable. Co-morbidities included food allergy (70%), allergic rhinitis (63%), eczema (50%), asthma (48%), sinusitis (31%), urticaria (30%), food anaphylaxis (28%), pneumonia (27%), autoimmune disease (5%), immunodeficiency (3%) and celiac disease (2.2%). Among those tested, food sensitization was very common (>80% sensitized to milk, soy, egg, nuts, barley, and/or rye) and to aeroallergens (51%). A large time lag in diagnosing EoE exists. Older patients have fibrostenotic features but similar inflammatory features. In addition to atopy, immune/infectious diseases, and diarrhea are reported more than expected in the general population, warranting further investigation.
Regional Myocardial Function during Acute Coronary Artery Occlusion and Its Modification by Pharmacologic Agents in the Dog
Authors: PIERRE THEROUX, DEAN FRANKLIN, JOHN ROSS, WILLIAM S. KEMPER
Journal: Circulation Research (1974)

Myocardial regional function during acute coronary artery occlusion was studied using ultrasonic dimension gauges in open-chest dogs. Three pairs of 2-mm ultrasonic crystals were implanted 1 cm apart near the endocardium in an ischemic segment, a control segment, and a segment at the margin of the ischemic zone. In the ischemic segment, coronary artery occlusion resulted in prompt dyskinesis which progressed to holosystolic expansion; length at enddiastole (diastolic length) increased by 11%, segment stroke work decreased by 91%, and the diastolic pressure-length relationship was displaced and steepened. In the marginal segment, active shortening and stroke work decreased by 37% and diastolic length increased by 4%. In the control segment, an initial increase in active shortening was observed, followed by compensatory operation of the Frank-Starling mechanism. Nitroglycerin administered during coronary artery occlusion decreased diastolic length and increased shortening in all three segments. An early beneficial effect of isoproterenol on all segments was later replaced by deterioration in marginal and ischemic segments. After propranolol administration, the decrease in shortening of the marginal segment was reduced to half of that observed during a control coronary artery occlusion, suggesting a protective effect of this drug. These results indicate the power of this approach, which provides continuous quantification of regional wall function in myocardial ischemia and during therapeutic interventions.