tbuckley/cabot-search huggingface dataset:
Radioisotopic Angiocardiography
Authors: JOSEPH P. KRISS, LEE P. ENRIGHT, WILLIAM G. HAYDEN, LEWIS WEXLER, NORMAN E. SHUMWAY
Journal: Circulation (1971)

Radioisotopic angiocardiography has been performed in 120 patients after the intravenous injection of 99m Tc pertechnetate. A scintillation camera and a variable time-lapse videoscintiscope were used. The results indicate that the method permits identification and physiologic assessment of a wide variety of congenital and acquired cardiovascular lesions, including septal defects, valvular stenosis and incompetence, aneurysm, tumor, venous obstruction, ventricular hypertrophy, and effusion. Emphasis particularly is given, therefore, to the wide scope of applicability of the procedure. The diagnostic criteria employed for a representative group of these lesions are presented together with illustrative examples to demonstrate the type and quality of the information which may be obtained with the method. The procedure is rapid and safe and does not require hospitalization, heart catheterization, or special preparation of the patient, advantages which favor its use as a diagnostic screening test. In addition to its diagnostic uses, radioisotopic angiography may offer a useful and convenient method of assessing the effects of therapy or of following the course of disease.
Hypermethylation of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer
Authors: J M D Wheeler
Journal: Gut (2001)

Ulcerative colitis associated colorectal cancer (UCACRC) has several distinctive clinicopathological and genetic features which differ from sporadic colorectal cancer (SCRC). Hypermethylation of the E-cadherin gene (CDH1) has not been described previously in colorectal cancer.A panel of SCRC and UCACRC were investigated for mutations in CDH1, and for hypermethylation of the promoter region of CDH1.DNA was available from 14 patients with UCACRC and from 14 with SCRC. All exons of CDH1 were amplified with the polymerase chain reaction (PCR) and screened using single strand conformational polymorphism and direct sequencing. Hypermethylation of the CDH1 promoter region was determined by methylation specific PCR following bisulphite modification, and compared with E-cadherin protein expression from a previous immunohistochemistry study.Thirteen of 28 cancers (46%) were hypermethylated in the CDH1 promoter region-eight cancers (57%) in the UCACRC group and five cancers (36%) in the SCRC group (NS)-and this correlated with reduced E-cadherin expression (p<0.05). There was a trend for methylation to be associated with a more advanced stage of cancer although this did not reach statistical significance. There were no mutations in CDH1 in either group although there were several polymorphisms.We have demonstrated hypermethylation of the promoter region in CDH1 in 46% of colorectal cancers studied. There was no difference between the UCACRC and SCRC groups. Just as there are specific differences in the genetic changes between UCACRC and SCRC, there is also likely to be a large degree of overlap among the genetic pathways of these cancers.
Induction of M3-Restricted Cytotoxic T Lymphocyte Responses by <i>N</i>-Formylated Peptides Derived from <i>Mycobacterium tuberculosis</i>
Authors: Taehoon Chun, Natalya V. Serbina, Dawn Nolt, Bin Wang, Nancy M. Chiu, JoAnne L. Flynn, Chyung-Ru Wang
Journal: The Journal of Experimental Medicine (2001)

Major histocompatibility complex (MHC) class I-restricted CD8(+) T cells play a critical role in the protective immunity against Mycobacterium tuberculosis (Mtb). However, only a few Mtb peptides recognized by MHC class Ia-restricted CD8(+) T cells have been identified. Information on epitopes recognized by class Ib-restricted T cells is even more limited. M3 is an MHC class Ib molecule that preferentially presents N-formylated peptides to CD8(+) T cells. Because bacteria initiate protein synthesis with N-formyl methionine, the unique binding specificity of M3 makes it especially suitable for presenting these particular bacterial epitopes. We have scanned the full sequence of the Mtb genome for NH2-terminal peptides that share features with other M3-binding peptides. Synthetic peptides corresponding to these sequences were tested for their ability to bind to M3 in an immunofluorescence-based peptide-binding assay. Four of the N-formylated Mtb peptides were able to elicit cytotoxic T lymphocytes (CTLs) from mice immunized with peptide-coated splenocytes. The Mtb peptide-specific, M3-restricted CTLs lysed the Mtb-infected macrophages effectively, suggesting that these N-formylated Mtb peptides are presented as the naturally processed epitopes by Mtb-infected cells. Furthermore, T cells from Mtb-infected lungs, spleen, and lymph nodes responded to N-formylated Mtb peptides in an M3-restricted manner. Taken together, our data suggest that M3-restricted T cells may participate in the immune response to Mtb.
Mechanism of interleukin 12-mediated toxicities during experimental viral infections: role of tumor necrosis factor and glucocorticoids.
Authors: J S Orange, T P Salazar-Mather, S M Opal, R L Spencer, A H Miller, B S McEwen, C A Biron
Journal: The Journal of Experimental Medicine (1995)

Interleukin 12 (IL-12) doses in excess of 100 ng/d have been shown to induce profound immunotoxicities in mice infected with lymphocytic choriomeningitis virus (LCMV). These immunotoxicities are characterized by almost complete inhibition of virus-induced CD8+ T cell expansion and CTL activation, and up to 2 log increases in viral replication. They are accompanied by induction of serum tumor necrosis factor (TNF). The studies presented here were undertaken to characterize mechanisms for the IL-12-induced toxicities and to examine expression and function of TNF in this context. Several physiological changes were induced in IL-12-treated uninfected and dramatically elevated in IL-12-treated virus-infected mice. IL-12 induced (a) decreases in body weights, &amp;gt; 10% in uninfected and &amp;gt; 20% in LCMV-infected mice; (b) elevation of circulating glucocorticoid levels to &amp;gt; 10 micrograms/dl in uninfected and &amp;gt; 20 micrograms/dl in infected mice; and (c) decreases in thymic mass, &amp;gt; 30% in uninfected and up to 95% in infected mice. These changes are known to be associated with circulating TNF. Northern blot and in situ hybridization analyses demonstrated that IL-12 induced TNF-alpha expression and that LCMV infection synergized with IL-12 for induction of this factor. Antibodies neutralizing TNF reversed all of the IL-12-induced toxicities in LCMV-infected mice including the immunotoxicities against CD8+ T cells and anti-viral defenses. The TNF-mediated immunotoxicities appeared to result from an induced cellular sensitivity to the factor, as splenic leukocytes and CD8+ T cell subsets isolated from LCMV-infected mice were more sensitive to TNF-mediated cytotoxicity in culture than were equivalent populations prepared from uninfected mice. Experiments with the glucocorticoid type II receptor antagonist, RU486, demonstrated that endogenous glucocorticoids were secondary intermediaries in IL-12-induced thymic atrophy. Studies in IL-2-deficient mice showed that the synergism was dependent upon endogenous IL-2. The results delineate a unique mechanism of TNF-mediated toxicity. In addition, they have significant implications concerning potential detrimental consequences of in vivo TNF induction and of IL-12 administration for protective anti-viral responses.
Pulmonary arterial hypertension and type-I glycogen-storage disease: the serotonin hypothesis
Authors: M. Humbert, P. Labrune, O. Sitbon, C. Le Gall, J. Callebert, P. Hervé, D. Samuel, R. Machado, R. Trembath, L. Drouet, J-M. Launay, G. Simonneau
Journal: European Respiratory Journal (2002)

A case of pulmonary arterial hypertension in a patient with type-Ia glycogen-storage disease, a rare autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase is reported in this study. It has been suggested that the occurrence of pulmonary arterial hypertension in type-Ia glycogen-storage disease could be due to an abnormal production of vasoconstrictive amines such as serotonin. To test this hypothesis, plasma serotonin concentrations were prospectively measured in 13 patients with type-Ia glycogen-storage disease, one patient with severe pulmonary hypertension and type-Ia glycogen-storage disease, 16 patients displaying severe pulmonary arterial hypertension, and 26 normal healthy controls. Elevated plasma serotonin concentrations were found in patients with either severe pulmonary arterial hypertension (38.8±7.3 nmol·L −1 ) or type-Ia glycogen-storage disease (36.8±11.5 nmol·L −1 ), as compared with controls (8.8±0.6 nmol·L −1 , p&lt;0.001). Plasma serotonin was dramatically elevated in the patient with type-Ia glycogen-storage disease and pulmonary arterial hypertension (113.4 nmol·L −1 ). It is concluded that type-Ia glycogen-storage disease may be another condition in which abnormal handling of serotonin is one event in a multistep process leading to severe pulmonary arterial hypertension.
HIV protease inhibitor ritonavir decreases endothelium-dependent vasorelaxation and increases superoxide in porcine arteries
Authors: B CONKLIN, W FU, P LIN, A LUMSDEN, Q YAO, C CHEN
Journal: Cardiovascular Research (2004)

Objective: Although HIV Protease inhibitors significantly reduce the viral load, they are associated with increased risk of cardiovascular disease. The aim of this study was to investigate the effects of HIV protease inhibitor ritonavir on vascular endothelial cell function. Methods: Porcine carotid arteries were perfusion-cultured for 24 h as controls or with 15 μM of ritonavir. Vessels were precontracted with norepinephrine followed by endothelium-dependent vasorelaxation with acetylcholine. Rings of vessels were cultured as controls or with ritonavir for 24 h and basal and NADPH-stimulated superoxide levels were determined using lucigenin-enhanced chemiluminescence. Superoxide levels in situ were also examined using dihydroethidium (DHE) staining, and nitrotyrosine levels were examined using a nitrotyrosine antibody. Results: Endothelium-dependent vasorelaxation was significantly reduced in ritonavir-treated vessels compared to controls. There were significant increases in basal and NADPH-stimulated superoxide production in vessel rings treated with ritonavir compared to control vessels. Dihydroethidium staining and nitrotyrosine staining were also elevated in endothelial cells of ritonavir-treated vessels, indicating increased superoxide production and increased oxidative stress, respectively, in ritonavir-treated vessels compared to controls. Conclusions: These data demonstrate that HIV protease inhibitor ritonavir causes a significant reduction in endothelium-dependent vasorelaxation in cultured porcine carotid arteries. Increased oxidative stress may be a possible mechanism of HIV protease inhibitor ritonavir-induced endothelial dysfunction.
Race, Grade Level, and Cigarette Smoking: The 1999 National Youth Tobacco Survey
Authors: D. L. Faulkner, M. C. Farrelly, J. C. Hersey
Journal: JNCI Journal of the National Cancer Institute (2000)

In the United States, the prevalence of cigarette smoking has remained consistently l ower a mong A fricanAmerican adolescents than among their white counterparts (1), and previous studies (2–4) have not been able to explain the race differential. One fruitful area of research is the examination of how the race gap varies by grade level. This information could provide direction for additional research on the topic. Therefore, a cross-sectional analysis of the 1999 National Youth Tobacco Survey (NYTS) was performed to answer the question, “At which grade level do race differences in adolescent cigarette smoking first become apparent?” The NYTS was designed to provide nationally representative data about tobacco use among students in grades 6–12. The 1999 NYTS was administered in the fall of 1999. More than 15 000 students completed anonymous, self-administered questionnaires in 131 schools across the country. The school response rate was 90%, and the student response rate was 93%, for an overall response rate of 84%. A weighting factor was applied to each student record to adjust for nonresponse and the various probabilities of selection, including
MPs accuse government of delaying and diluting antidiscrimination law for disabled people
Authors: A. O'Dowd
Journal: BMJ (2009)

The government is stalling on implementing antidiscrimination legislation that would help disabled people, a report from MPs and peers says.

Parliament’s Joint Committee on Human Rights has published a report that heavily criticises the government’s delays in ratifying the United Nations’ Convention on the Rights of Persons with Disabilities.

The convention was agreed in 2006 and came into force in May of last year as an agreement to build on existing international human rights instruments, guaranteeing equal treatment for disabled people in education, employment, and all areas of life.

The United Kingdom was closely involved in negotiating and agreeing the convention and …
Socioeconomic Inequalities in Injury: Critical Issues in Design and Analysis
Authors: Catherine Cubbin, Gordon S. Smith
Journal: Annual Review of Public Health (2002)

▪ Abstract Injuries continue to place a tremendous burden on the public's health and rates vary widely among different groups in the population. Increasing attention has recently been given to the effects of socioeconomic status (SES) as a determinant of health among both individuals and communities. However, relatively few studies have focused on the influence of SES and injuries. Furthermore, those that have, and the other injury studies that have included measures of SES in their analysis, have varying degrees of conceptual and methodological rigor in their use of this measure. Recent advances in data linkage and analytic techniques have, however, provided new and improved methods to assess the relationship between SES and injuries. This review summarizes the relevant literature on SES and injuries, with particular attention to study design, and the measurement and interpretation of SES. We found that increasing SES has a strong inverse association with the risk of both homicide and fatal unintentional injuries, although the results for suicide were mixed. However, the relationship between SES and nonfatal injuries was less consistent than for fatal injuries. We offer potential explanatory mechanisms for the relationship between SES and injuries and make recommendations for future research in this area.
MitoKATP channel activation suppresses gap junction permeability in the ischemic myocardium by an ERK-dependent mechanism
Authors: K NAITOH, Y ICHIKAWA, T MIURA, Y NAKAMURA, T MIKI, Y IKEDA, H KOBAYASHI, M NISHIHARA, K OHORI, K SHIMAMOTO
Journal: Cardiovascular Research (2006)

Background Ischemic preconditioning accelerates suppression of gap junction (GJ) permeability during myocardial ischemia, and GJ blockers reduce infarct size. We hypothesized that the mitochondrial ATP-sensitive K+ (mitoKATP) channel is one of the mechanisms regulating GJ permeability through the mitogen-activated protein kinase ERK, leading to cardioprotection.
Hyperphosphorylation of RyRs Underlies Triggered Activity in Transgenic Rabbit Model of LQT2 Syndrome
Authors: Dmitry Terentyev, Colin M. Rees, Weiyan Li, Leroy L. Cooper, Hitesh K. Jindal, Xuwen Peng, Yichun Lu, Radmila Terentyeva, Katja E. Odening, Jean Daley, Kamana Bist, Bum-Rak Choi, Alain Karma, Gideon Koren
Journal: Circulation Research (2014)

Rationale: Loss-of-function mutations in human ether go-go (HERG) potassium channels underlie long QT syndrome type 2 (LQT2) and are associated with fatal ventricular tachyarrhythmia. Previously, most studies focused on plasma membrane–related pathways involved in arrhythmogenesis in long QT syndrome, whereas proarrhythmic changes in intracellular Ca 2+ handling remained unexplored. Objective: We investigated the remodeling of Ca 2+ homeostasis in ventricular cardiomyocytes derived from transgenic rabbit model of LQT2 to determine whether these changes contribute to triggered activity in the form of early after depolarizations (EADs). Methods and Results: Confocal Ca 2+ imaging revealed decrease in amplitude of Ca 2+ transients and sarcoplasmic reticulum Ca 2+ content in LQT2 myocytes. Experiments using sarcoplasmic reticulum–entrapped Ca 2+ indicator demonstrated enhanced ryanodine receptor (RyR)–mediated sarcoplasmic reticulum Ca 2+ leak in LQT2 cells. Western blot analyses showed increased phosphorylation of RyR in LQT2 myocytes versus controls. Coimmunoprecipitation experiments demonstrated loss of protein phosphatases type 1 and type 2 from the RyR complex. Stimulation of LQT2 cells with β-adrenergic agonist isoproterenol resulted in prolongation of the plateau of action potentials accompanied by aberrant Ca 2+ releases and EADs, which were abolished by inhibition of Ca 2+ /calmodulin-dependent protein kinase type 2. Computer simulations showed that late aberrant Ca 2+ releases caused by RyR hyperactivity promote EADs and underlie the enhanced triggered activity through increased forward mode of Na + /Ca 2+ exchanger type 1. Conclusions: Hyperactive, hyperphosphorylated RyRs because of reduced local phosphatase activity enhance triggered activity in LQT2 syndrome. EADs are promoted by aberrant RyR-mediated Ca 2+ releases that are present despite a reduction of sarcoplasmic reticulum content. Those releases increase forward mode Na + /Ca 2+ exchanger type 1, thereby slowing repolarization and enabling L-type Ca 2+ current reactivation.
Treatment of acute ankle sprains: evidence on the use of an ankle brace is unclear
Authors: Irene L C Heijnders, Chung-Wei Christine Lin
Journal: British Journal of Sports Medicine (2012)

▸ Kemler E , van de Port I, Backx F, et al. A systematic review on the treatment of acute ankle sprain: brace versus other functional treatment types. Sports Med 2011; 41 :185–97.

Ankle sprains are common, with an incidence of 60–70 per 10 000.1 Functional treatment (ie, brace, bandage or tape that allows some exercise or walking) appears more efficacious than cast immobilisation after ankle sprain,2 ,3 but the optimal type of functional treatment is unclear. A 2002 Cochrane systematic review reported a significantly shorter period in returning to work and sports if ankle braces rather than elastic bandages were used.3 However, this review included few studies and more studies are now available.4

The aim was to evaluate the effectiveness of ankle braces when compared with other functional treatment for acute ankle sprains.

The search was conducted in four databases (PubMed, EMBASE, CINAHL and CENTRAL) and the reference lists of included studies. All randomised and quasi-randomised controlled trials, published between 1990 and April 2009, written in English, Dutch or …
Transmission of glioblastoma multiforme following bilateral lung transplantation from an affected donor: Case study and review of the literature
Authors: Mary Y. Armanios, Stuart A. Grossman, Stephen C. Yang, Barbara White, Arie Perry, Peter C. Burger, Jonathan B. Orens
Journal: Neuro-Oncology (2004)

Donor-acquired solid organ malignancy is a rare complication of organ transplantation. We report a case of a patient who received bilateral lung transplants for pulmonary fibrosis from a donor with known glioblastoma multiforme (GBM). The lungs, heart, liver, and kidneys were harvested after a lethal intracranial bleed and accepted for transplantation by four centers. An enlarged hilar lymph node sampled at the time of transplant was found to contain GBM. Four months later, the patient developed diffuse interstitial pulmonary infiltrates with mediastinal lymphadenopathy. Lung biopsy confirmed metastatic GBM. The patient died 2 weeks after the diagnosis was established. The patient receiving the donor liver also developed GBM. We present a case study, review of the literature, and suggested interventions to minimize the risk of transmission.
COMMUNITY PLANNING AS A SUPPORT TO TREATMENT
Authors: M. J. ROCKMORE, ELIAS J. MARSH
Journal: American Journal of Psychiatry (1960)

To recapitulate, the necessity for adequate planning is justified not only by current scientific knowledge that indicates its validity, but also by the practical necessity for making the most efficient use of any and all available resources. When we total our current scientific knowledge we hear that "much of the disability in mental illness is superimposed by social and treatment mechanisms and is preventable and reversible" (9). A review of financing (tax funds supply probably 90% of the budgets for services) tells us that "discussion focuses on assertions that the states have reached their taxing limits"(10). When we examine our personnel picture and the training and recruitment prospects (11) we find that it will take all our ingenuity to stand still. These are sobering and responsibly drawn conclusions. They indicate that we cannot expect more of what we have, without limit. We cannot assume that our currently uncoordinated efforts are making maximum use of existing facilities. We must continue to discover and make creative use of related facilities which can contribute to the solutions of our problems. This assumes that we have defined our problems in both qualitative and quantitative terms; that we have an appreciation of our resources and that the means of communication exists to consider getting the two together (12). This is a large assumption. Nevertheless it is the only base on which planning can define and consider the issues. The alternative is to continue our buckshot approach of more of the same, in the hope that if some is good, a lot is better. Planning can start with the individual practitioner out of whatever professional discipline he represents. He is in a position to appreciate the needs evidenced in the individual case. Through his relationship with his colleagues in membership organizations or through hospital and agency structures these individual needs become cumulative and are communicated. (We have herein noted how this chain reaction can move from the National scene to the clinical decision.) As the needs of individuals become clear it is possible to design and implement services to meet these needs. From private practice case planning up the line to broad program planning, reality factors must be identified and met. The reality variables may well be decisive in determining whether or not our technical skills will have an opportunity to deal with personality pathology or its manifestations!