tbuckley/cabot-search huggingface dataset:
Molecular Pathways: Radiation-Induced Cognitive Impairment
Authors: Dana Greene-Schloesser, Elizabeth Moore, Mike E. Robbins
Journal: Clinical Cancer Research (2013)

Abstract Each year, approximately 200,000 patients in the United States will receive partial- or whole-brain irradiation for the treatment of primary or metastatic brain cancer. Early and delayed radiation effects are transient and reversible with modern therapeutic standards; yet, late radiation effects (≥6 months postirradiation) remain a significant risk, resulting in progressive cognitive impairment. These risks include functional deficits in memory, attention, and executive function that severely affect the patient's quality of life. The mechanisms underlying radiation-induced cognitive impairment remain ill defined. Classically, radiation-induced alterations in vascular and neuroinflammatory glial cell clonogenic populations were hypothesized to be responsible for radiation-induced brain injury. Recently, preclinical studies have focused on the hippocampus, one of two sites of adult neurogenesis within the brain, which plays an important role in learning and memory. Radiation ablates hippocampal neurogenesis, alters neuronal function, and induces neuroinflammation. Neuronal stem cells implanted into the hippocampus prevent the decrease in neurogenesis and improve cognition after irradiation. Clinically prescribed drugs, including PPARα and PPARγ agonists, as well as RAS blockers, prevent radiation-induced neuroinflammation and cognitive impairment independent of improved neurogenesis. Translating these exciting findings to the clinic offers the promise of improving the quality of life of brain tumor patients who receive radiotherapy. Clin Cancer Res; 19(9); 2294–300. ©2013 AACR.
Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin.
Authors: Y Merrouche, S Negrier, C Bain, V Combaret, A Mercatello, B Coronel, J F Moskovtchenko, P Tolstoshev, R Moen, T Philip
Journal: Journal of Clinical Oncology (1995)

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) has been reported to mediate tumor regression in some human cancers. To define better the biologic characteristics of TIL, especially survival and distribution in vivo, we performed a gene-marker study in patients with advanced malignancies.We treated five patients with metastatic melanoma or renal cell carcinoma with adoptive immunotherapy. TIL were genetically modified, before their infusion, using a recombinant retroviral vector that contained the marker gene coding for resistance to neomycin (NeoR).All of the patients tolerated the treatment well and none of the theoretic safety hazards due to the retroviral gene transduction was observed. The presence of the NeoR gene in TIL was detected by Southern blot analysis, with an efficiency of transduction that ranged from 1% to 26%. With polymerase chain reaction (PCR) analysis, we demonstrated that gene-modified TIL can survive for several months after reinjection, since positive blood samples were observed up to day 260 following reinjection. Eight malignant biopsy specimens were obtained from three patients after cell infusion. TIL were detected in only four of these eight tumor deposits on days 7 and 260.These results confirm the feasibility and safety of using in vitro retroviral gene transduction in human lymphocytes to analyze their in vivo distribution for further therapeutic applications. However, a selective and prolonged retention of TIL at the tumor site was not found in this study.
Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system.
Authors: O Nakagawa, I Tanaka, T Usui, M Harada, Y Sasaki, H Itoh, T Yoshimasa, T Namba, S Narumiya, K Nakao
Journal: Circulation (1994)

BACKGROUND Prostacyclin elicits a potent vasodilation and inhibition of platelet aggregation through binding to its membrane receptor. The impairment of prostacyclin receptor activity is implicated in various human cardiovascular diseases. In the present study, we succeeded in the isolation and characterization of human prostacyclin receptor cDNA and elucidated its gene expression in human tissues. METHODS AND RESULTS We isolated a cDNA clone encoding the human prostacyclin receptor from a human lung cDNA library. The isolated cDNA clone encodes a 386-amino acid protein with seven putative transmembrane domains, which belongs to the G protein-coupled receptor superfamily. [3H]iloprost, a prostacyclin receptor agonist, specifically bound to the receptor transiently expressed in COS-7 cells. The binding was inhibited in the rank order of iloprost = cicaprost, another prostacyclin receptor agonist, &gt; prostaglandin E1 (PGE1) &gt; PGE2, PGF2 alpha, PGD2, STA2. In addition, iloprost dose-dependently stimulated cAMP generation in these COS-7 cells. These results are consistent with the characteristics of the human prostacyclin receptor. Northern blotting analysis on human tissues revealed that prostacyclin receptor mRNA is abundantly expressed in the aorta, lung, atrium, ventricle, and kidney. CONCLUSIONS We cloned human prostacyclin receptor cDNA and elucidated its abundant gene expression in the human cardiovascular system. The present study will lead to better understanding of the significance of prostacyclin in humans and further facilitate the clinical application of prostacyclin.
Behavioral and Psychosocial Interventions in Diabetes
Authors: Mark Peyrot, Richard R. Rubin
Journal: Diabetes Care (2007)

A major task of diabetes care providers is to support patients in performing necessary self-care behaviors using well-accepted strategies such as recommending effective self-care regimens and educating patients in their use. Also critical are behavioral interventions that help patients implement self-care regimens in the face of life's exigencies.

The purpose of this article is to identify key behavioral/psychosocial interventions available to diabetes care providers. We present a conceptual framework for organizing the application of these interventions, focusing on practical interventions that can be implemented by a typical health care provider, including referral to a behavioral/psychosocial specialist where this seems the most practical choice.

A typical office visit lasts only 15 min (1). Therefore, feasibility is an important consideration in evaluating patient care recommendations. The strategies we propose should be no more time-consuming than these approaches, which are highly recommended for their feasibility. A previously demonstrated, effective counseling strategy for weight loss can be maintained by 15-min visits (2). A behavior change support approach, the 5As (ask, advise, assess, assist, arrange) Model, is estimated to take less than half the time of a normal office visit (3). An emotional support approach, the BATHE (background, affect, trouble, handling, empathy) Model, is estimated to take ∼15 min (4).

Feasibility must also be assessed in terms of what it costs to ignore psychosocial problems or to employ an ineffective approach to behavior change. Patients who have psychological problems use health services more intensively, and if patients do not change their behavior, the clinician must spend time dealing with the problem at subsequent visits. Finally, research suggests that dealing with patients' concerns does not require additional time if done correctly (5). Thus, effective clinical procedure may also be efficient.

The review we present is not exhaustive. We do not discuss all interventions that have …
Escherichia coli Antibody: A Screening Test for Immunodeficiency
Authors: A. D. B. Webster, T. Efter, G. L. Asherson
Journal: BMJ (1974)

Six patients suffering from recurrent chest infections were found to lack antibodies to a pooled antigen obtained from six different serotypes of commensal Escherichia coli bacteria. All had normal serum IgG concentrations, but five subsequently benefited from regular gammaglobulin injections. We suggest that the absence of such E. coli antibodies usually indicates a clinically significant defect in antibody production. This simple screening test is of use in the diagnosis of primary and secondary immunodeficiency disorders.
Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: a Groupe d'Etude des Lymphomes de l'Adulte (GELA) study
Authors: J. Dupuis, J.-F. Emile, N. Mounier, C. Gisselbrecht, N. Martin-Garcia, T. Petrella, R. Bouabdallah, F. Berger, A. Delmer, B. Coiffier, F. Reyes, P. Gaulard
Journal: Blood (2006)
Innate talents: A psychological tautology?
Authors: Sidney H. Irvine
Journal: Behavioral and Brain Sciences (1998)

The tautological implications of “innate talents” are outlined. Analogies are drawn between the present review and the nature–nurture controversies of 40 years ago. Ferguson's (1954; 1956) theoretical positions are proposed as a context in which to consider present and future attempts to resolve this long-standing issue.
Patient participation in medical decision-making: A French study in adjuvant radio-chemotherapy for early breast cancer
Authors: C. Protière, P. Viens, D. Genre, D. Cowen, J. Camerlo, G. Gravis, C. Alzieu, F. Bertucci, M. Resbeut, D. Maraninchi, J.-P. Moatti
Journal: Annals of Oncology (2000)
The Incidence of Dementia in England and Wales: Findings from the Five Identical Sites of the MRC CFA Study
Authors: Fiona Matthews, Carol Brayne
Journal: PLoS Medicine (2005)

Background Although incidence of dementia is known to vary between nations, variation within country has not been explored because most incidence studies are single site or have insufficient numbers to compare sites. Few countries have conducted multisite incidence studies in order to facilitate national comparisons. This study aims to provide robust measures of the variation of the incidence of dementia across sites within England and Wales and produce overall estimates by age and sex. Methods and Findings The Medical Research Council Cognitive Function and Ageing Study used identical methodology in five diverse sites across the United Kingdom, each with different risk patterns and mortality rates. Incidence has been estimated using likelihood-based methods between the first two waves of interviews. Incidence rates rise with age, particularly above the age of 75 y, from 7.4 (95 confidence interval, 3.616.1) per 1,000 person years at age 6569 y to 84.9 (95 confidence interval, 63.0107.8) per 1,000 person years at age 85 y and above. The rate of increase for both sexes is marked, and continues into the oldest age groups. Hence, it is estimated that approximately 180,000 new cases of dementia occur in England and Wales each year. There is no convincing evidence of variation across sites, and incidence rates do not reflect the variations in the prevalence of possible risk factors in these sites. Conclusion There is no evidence, within England and Wales, of variation in dementia incidence across sites. Dementia incidence rates do not tail off at the oldest ages.
The cellular composition of induced sputum in chronic obstructive pulmonary disease
Authors: R.A. Peleman, P.H. Rytilä, J.C. Kips, G.F. Joos, R.A. Pauwels
Journal: European Respiratory Journal (1999)

Asthma and chronic obstructive pulmonary disease are characterized by airway inflammation, which can be assessed by bronchoscopic techniques as well as by the analysis of induced sputum. A method to induce sputum with inhaled hypertonic saline was adapted for use in 21 chronic obstructive pulmonary disease (COPD) patients (mean baseline forced expiratory volume in one second (FEV1) 1.60 L, or 54% predicted) and in 16 healthy volunteers. The success rate and safety of the method, were investigated along with the reproducibility of cell counts and differences in cell counts between both groups. All subjects produced adequate samples and the procedure did not alter spirometric values. A marked sputum neutrophilia was noted in patients with COPD (74.9+/-4.7%), whereas mainly macrophages were seen in healthy volunteers (74.0+/-4.0%). Reliability of the cell counts was high, both within investigators (r=0.99 neutrophils, r=0.99 macrophages) and between investigators (r=0.95 neutrophils, r=0.77 macrophages). In patients with COPD, an inverse correlation was noted between percentage of neutrophils and FEV1 (r(s)=-0.48, p<0.05). Immunostaining revealed a large proportion of activated macrophages in both groups. It was concluded that induction of sputum is a safe and reproducible method to study the composition of airway secretions in patients with chronic obstructive pulmonary disease.
Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database
Authors: U A Walker, A Tyndall, L Czirjak, C Denton, D Farge-Bancel, O Kowal-Bielecka, U Muller-Ladner, C Bocelli-Tyndall, M Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment, the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. <b>Aims and methods:</b> EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the American College of Rheumatology diagnostic criteria in participating centres. We aimed to characterise demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. <b>Results:</b> In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were women. On multivariate analysis, scleroderma subsets (dcSSc vs lcSSc), antibody status and age at onset of Raynaud's phenomenon, but not gender, were found to be independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis was more closely associated with clinical manifestations than were SSc subsets. <b>Conclusion:</b> dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction seemed to be superseded by an antibody-based classification in predicting some scleroderma complications. The EUSTAR MEDS database facilitates the analysis of clinical patterns in SSc, and contributes to the standardised assessment and monitoring of SSc internationally.
Regression of Glioma in Rat Models by Intranasal Application of Parvovirus H-1
Authors: Irina Kiprianova, Nadja Thomas, Ali Ayache, Manuel Fischer, Barbara Leuchs, Michèle Klein, Jean Rommelaere, Jörg R. Schlehofer
Journal: Clinical Cancer Research (2011)

In previous studies, we have shown that the apathogenic rat parvovirus H-1 (H-1PV) is capable to induce regression of advanced symptomatic rat and human gliomas in a rat model, when the virus was injected in the tumor (intracranially) or intravenously. Infection with H-1PV did not provoke any pathology in nontumor tissue. This study addresses the question whether also intranasal application of this oncolytic virus is suitable and sufficient for treating gliomas in this animal model.Rat (RG-2) or human (U87) glioma cells were grafted stereotactically in the brain of rats (Wistar or RNU, respectively), and after development of tumors visible by MRI, H-1PV was instilled intranasally. Tumor regression was monitored by MRI, and survival was analyzed by Kaplan-Meier analysis. Brains from sacrificed animals were analyzed for histologic alterations, presence of viral DNA and proteins and infectious virions. In addition, distribution of virus to other organs was determined.A single intranasal instillation of H-1PV was sufficient to induce efficient regression of rat glioma, leading to significant prolongation of survival without any toxicity for other tissues. It is shown that the virus reaches brain and other tissues, and that the viral replication-associated (and oncolysis-associated) regulatory proteins are exclusively expressed in the tumor tissue. In rats with xenografts of human glioma, oncolytic activity of H-1PV was less pronounced, however, leading to significant prolongation of survival.In view of an ongoing clinical trial on the use of H-1PV for oncolytic virotherapy of glioma, the option of applying the virus intranasally may be a valuable alternative to invasive routes of infection.
Stimulation of soluble guanylate cyclase by an acetylcholine-induced endothelium-derived factor from rabbit and canine arteries.
Authors: U Förstermann, A Mülsch, E Böhme, R Busse
Journal: Circulation Research (1986)

The present study was designed to investigate the hypothesis that, during acetylcholine-induced endothelium-dependent relaxation, a factor(s) is released from endothelial cells which directly activates soluble guanylate cyclase. We attempted to determine what similarities or differences existed between this factor and endothelium-derived relaxing factor. The study was performed on segments of rabbit aorta and canine femoral artery. Purified soluble guanylate cyclase was injected into the lumen of these vascular segments, together with its substrate, for intraluminal incubation of the enzyme. In endothelium-intact vascular segments, the activity of guanylate cyclase was enhanced over control values obtained by incubation in test tubes. The stimulation was further increased by acetylcholine in concentrations which caused relaxation of the vascular segments. The stimulating principle could not be transferred from the vessel lumen to an external solution of guanylate cyclase, indicating a short life-time. Removal of the endothelium prevented formation and release of the guanylate cyclase stimulating factor(s). Atropine, mepacrine, or nordihydroguaiaretic acid, which inhibit acetylcholine-induced endothelium-dependent relaxations, also inhibited acetylcholine-induced endothelium-mediated activation of guanylate cyclase. The results support the hypothesis that acetylcholine-induced endothelium-derived relaxing factor increases cyclic guanosine monophosphate levels of vascular smooth muscle by a stimulation of soluble guanylate cyclase.
Myocardial Infarct Extension: Occurrence, Outcome, and Risk Factors in the Multicenter Investigation of Limitation of Infarct Size
Authors: James E. Muller, Robert E. Rude, Eugene Braunwald, Tyler D. Hartwell, Robert Roberts, Burton E. Sobel, Cynthia Ritter, Corette B. Parker, Allan S. Jaffe, Peter H. Stone, Daniel S. Raabe, James T. Willerson, Thomas Robertson
Journal: Annals of Internal Medicine (1988)

The occurrence, outcome, and predictors of myocardial infarct extension were determined in 848 patients with acute myocardial infarction. An increase in the level of plasma MB creatine kinase activity was used to detect extension, which occurred in 71 of 848 patients (8.4%). For these patients, hospital mortality was more than four times higher than for those without extension (30% versus 7%, P < 0.01). However, for patients surviving the initial hospitalization, there was no significant difference in mortality during the following year (12% compared with 9%). Multivariable analyses indicated that extension was more likely to occur in patients with recurrent ischemic pain during the second hospital day, a history of previous myocardial infarction, and ST segment depression on the admission electrocardiogram. The occurrence of extension in patients with two of these risk factors was more than twice that of patients without any of the risk factors (15.1% compared with 5.8%). Patients with these risk factors should be considered for early coronary angiography and possible intervention to prevent infarct extension and its sequellae.
Heterogeneous response of antimitochondrial autoantibodies and bile duct apical staining monoclonal antibodies to pyruvate dehydrogenase complex E2: The molecule versus the mimic
Authors: Chris Migliaccio, Judy Van de Water, Aftab A. Ansari, Marshall M. Kaplan, Ross L. Coppel, Kit S. Lam, Richard K. Thompson, Freda Stevenson, Eric M. Gershwin
Journal: Hepatology (2001)

The 2–oxo–acid dehydrogenase complexes and, in particular, the E2 component of the pyruvate dehydrogenase complex (PDC) are the target of antimitochondrial antibodies (AMA). More than 95% of primary biliary cirrhosis (PBC) patients have detectable levels of autoantibodies to PDC–E2 and in general these react with a region of the molecule that contains the prosthetic group lipoic acid (LA). LA is vital to the function of the enzyme, although there is conflicting evidence as to whether its presence is required for PDC–E2 recognition by AMA. Some, but not all, monoclonal antibodies (mAbs) to PDC–E2 produce an intense staining pattern at the apical surface of bile duct epithelial cells (BEC) in patients with PBC, and it has been argued that the molecule at the apical surface of PBC bile duct cells is a modified form of PDC–E2 or a cross–reactive molecule, acting as a molecular mimic. Herein, we characterize the epitopes recognized by 4 anti-PDC–E2 mAbs that give apical staining patterns (3 mouse and 1 human). In particular, by using a combination of recombinant antigens, competitive inhibition assays, and a unique peptide–on–bead assay, we determined that these apically staining mAbs recognize 3 or 4 distinct epitopes on PDC–E2. More importantly, this suggests that a portion spanning the entire inner lipoyl domain of PDC–E2 can be found at the BEC apical surface. In addition, competition assays with patient sera and a PDC–E2-specific mAb showed significant epitope overlap with only 1 of the 3 mouse mAbs and showed a differential response to the peptide bound to beads. These findings further highlight the heterogeneous response of patient autoantibodies to the inner lipoyl domain of PDC–E2. (Hepatology 2001;33:792–801.)