tbuckley/cabot-search huggingface dataset:
INHIBITION OF GASTRIN AND GASTRIC-ACID SECRETION BY GROWTH-HORMONE RELEASE-INHIBITING HORMONE
Authors: S.R Bloom, C.H Mortimer, M.O Thorner, G.M Besser, R Hall, A Gomez-Pan, V.M Roy, R.C.G Russell, D.H Coy, A.T Kastin, A.V Schally
Journal: The Lancet (1974)
The 'GALS' locomotor screen.
Authors: M Doherty, J Dacre, P Dieppe, M Snaith
Journal: Annals of the Rheumatic Diseases (1992)

The locomotor system is complex and difficult to examine. A selective clinical process to detect important locomotor abnormalities and functional disability could prove valuable. A screen based on a tested 'minimal' history and examination system is described, together with a simple method of recording. The screen is fast and easy to perform. As well as providing a useful introduction to examination of the locomotor system, the screen includes objective observation of functional movements relevant to activities of daily living. Its inclusion in the undergraduate clerking repertoire could improve junior doctors' awareness and recognition of rheumatic disease and general disability. It could also provide a valuable screening test for use in general practice.
MYOCARDIAL NECROSIS PRODUCED IN ANIMALS BY MEANS OF CRYSTALLINE STREPTOCOCCAL PROTEINASE
Authors: Aaron Kellner, Theodore Robertson
Journal: The Journal of Experimental Medicine (1954)

Focal myocardial necrosis that was often extensive was found in a high percentage of rabbits, guinea pigs, and mice given a single intravenous injection of crystalline streptococcal proteinase. The findings are discussed in relation to their possible implications for the pathogenesis of the cardiac lesions of rheumatic fever.
The promise of gene therapy in gastrointestinal and liver diseases
Authors: J Prieto
Journal: Gut (2003)

Gene therapy consists of the transfer of genetic material to cells to achieve a therapeutic goal. In the field of gastroenterology and hepatology gene therapy has produced considerable expectation as a potential tool in the management of conditions that lack effective therapy including non-resectable neoplasms of the liver, pancreas and gastrointestinal tract, chronic viral hepatitis unresponsive to interferon therapy, liver cirrhosis, and inflammatory bowel disease.
Cumulative Use of Strong Anticholinergics and Incident Dementia
Authors: Shelly L. Gray, Melissa L. Anderson, Sascha Dublin, Joseph T. Hanlon, Rebecca Hubbard, Rod Walker, Onchee Yu, Paul K. Crane, Eric B. Larson
Journal: JAMA Internal Medicine (2015)

Many medications have anticholinergic effects.In general, anticholinergicinduced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy.However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia.OBJECTIVE To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTSProspective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington.We included 3434 participants 65 years or older with no dementia at study entry.Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003.Beginning in 2004, continuous replacement for deaths occurred.All participants were followed up every 2 years.Data through September 30, 2012, were included in these analyses.EXPOSURES Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years.The most recent 12 months of use was excluded to avoid use related to prodromal symptoms.Cumulative exposure was updated as participants were followed up over time.MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer disease using standard diagnostic criteria.Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities. RESULTSThe most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics.During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease).A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001).For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16)for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51)for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62)for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96)for TSDDs greater than 1095.A similar pattern of results was noted for Alzheimer disease.Results were robust in secondary, sensitivity, and post hoc analyses. CONCLUSIONS AND RELEVANCEHigher cumulative anticholinergic use is associated with an increased risk for dementia.Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.
Increased N-Myristoyltransferase Activity Observed in Rat and Human Colonic Tumors
Authors: B. A. Magnuson, R. V. S. Raju, T. N. Moyana, R. K. Sharma
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Colorectal cancer is one of the leading causes of cancer death in North America. Since treatment of colonic cancer remains difficult because of the lack of effective chemotherapeutic agents, it is important to continue to search for cellular functions that can be disrupted by chemotherapeutic drugs and inhibit the development or progression of this disease. Modification of proteins by myristoylation has been recognized as important in the function of various viral, oncogenic, and signal-transduction proteins and thus has been proposed as a target for chemotherapeutic drug design. However, the activity of the enzyme that catalyzes this modification, N -myristoyltransferase, has not been investigated in cancer relative to normal tissue. Purpose : The Purpose of this study was twofold: 1) to investigate the activity of N -myristoyltransferase in azoxymethane-induced rat colonic cancer tissue compared with normal and normal-appearing rat colonic tissue and 2) to determine if similar differences would be observed in a small sample of human colonic tumors. Methods : N -Myristoyltransferase activity was determined in 45 colonic tissue specimens from Sprague-Dawley rats—10 given injections of the colon carcinogen, azoxymethane, and three untreated. Tissue specimens included 35 colonic tumors of varying pathologic stages, seven specimens of normal-appearing adjacent mucosa, and three specimens of normal colonic mucosa. Colectomy specimens from five patients were assayed for N -my-ristoyltransferase activity. Subcellular distribution of N -myristoyltransferase activity was determined. Synthetic peptides of known myristoylated proteins—pp60 src and cyclic adenosine monophosphate-dependent protein kinase—were used in kinetic analyses of N -myristoyltransferase in colonic cancer and normal-appearing colonic tissue. All P values are two-tailed. Results : N -Myristoyltransferase activity was increased in rat colonictumors compared with normal-appearing adjacent mucosa and normal mucosa ( P = .0002). Elevation of N -myristoyltransferase activity was present in all tumors, including colonic polyps. Increased N -myristoyltransferase activity was also observed in human colonic tumors and was predominantly cytosolic. N -Myristoyltransferase of colonic cancer tissues had a similar Michaelis constant but an approximate twofold higher maximum velocity for both the pp60 src - and cyclic adenosine monophosphate-dependent protein kinase-derived peptides compared with N -myristoyltransferase of normal-appearing tissue. Conclusions : This study demonstrates for the first time that N -myristoyltransferase activity is higher in colonic epithelial neoplasms than in normal-appearing colonic tissue and that an increase in N -myristoyltransferase activity appears at an early stage in colonic carcinogenesis. [J Natl Cancer Inst 1995;87:1630–5]
Multiple Functions of Endocannabinoid Signaling in the Brain
Authors: István Katona, Tamás F. Freund
Journal: Annual Review of Neuroscience (2012)

Despite being regarded as a hippie science for decades, cannabinoid research has finally found its well-deserved position in mainstream neuroscience. A series of groundbreaking discoveries revealed that endocannabinoid molecules are as widespread and important as conventional neurotransmitters such as glutamate or GABA, yet they act in profoundly unconventional ways. We aim to illustrate how uncovering the molecular, anatomical, and physiological characteristics of endocannabinoid signaling has revealed new mechanistic insights into several fundamental phenomena in synaptic physiology. First, we summarize unexpected advances in the molecular complexity of biogenesis and inactivation of the two endocannabinoids, anandamide and 2-arachidonoylglycerol. Then, we show how these new metabolic routes are integrated into well-known intracellular signaling pathways. These endocannabinoid-producing signalosomes operate in phasic and tonic modes, thereby differentially governing homeostatic, short-term, and long-term synaptic plasticity throughout the brain. Finally, we discuss how cell type- and synapse-specific refinement of endocannabinoid signaling may explain the characteristic behavioral effects of cannabinoids.
Fibroblast growth factor-2 (FGF2) and syndecan-1 (SDC1) are potential biomarkers for putative circulating CD15+/CD30+ cells in poor outcome Hodgkin lymphoma patients
Authors: Rajendra Gharbaran, Andre Goy, Takemi Tanaka, Jongwhan Park, Chris Kim, Nafis Hasan, Swathi Vemulapalli, Sreeja Sarojini, Madalina Tuluc, Kip Nalley, Pritish Bhattacharyya, Andrew Pecora, K Stephen Suh
Journal: Journal of Hematology & Oncology (2013)

High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment.Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples representing good and poor outcomes were analyzed by qRT-PCR, immunohistochemical (IHC), and immunofluorescence analyses.To identify predictive HL-specific biomarkers, potential marker genes selected using bioinformatics approaches were screened against HL cell lines and HL patient samples. Fibroblast Growth Factor-2 (FGF2) and Syndecan-1 (SDC1) were overexpressed in all HL cell lines, and the overexpression was HL-specific when compared to 116 non-Hodgkin lymphoma tissues. In the analysis of stratified NS-cHL patient samples, expression of FGF2 and SDC1 were 245 fold and 91 fold higher, respectively, in the poor outcome (PO) group than in the good outcome (GO) group. The PO group exhibited higher expression of the HL marker CD30, the macrophage marker CD68, and metastatic markers TGFβ1 and MMP9 compared to the GO group. This expression signature was confirmed by qualitative immunohistochemical and immunofluorescent data. A Kaplan-Meier analysis indicated that samples in which the CD30+ cells carried an FGF2+/SDC1+ immunophenotype showed shortened survival. Analysis of chemo-naive HL blood samples suggested that in the PO group a subset of CD30+ HL cells had entered the circulation. These cells significantly overexpressed FGF2 and SDC1 compared to the GO group. The PO group showed significant down-regulation of markers for monocytes, T-cells, and B-cells. These expression signatures were eliminated in heavily pretreated patients.The results suggest that small subsets of circulating CD30+/CD15+ cells expressing FGF2 and SDC1 represent biomarkers that identify NS-cHL patients who will experience a poor outcome (primary refractory and early relapsing).
Accidental gonococcal infection of the eyes in children.
Authors: J O Doyle
Journal: BMJ (1972)

confirmation chlorpropamide levels of 16 mg and 14 mg/100 ml were found in two blood samples taken at a two-day interval at a time when she was having repeated hypoglycaemic episodes.These levels were equivalent to about a 5-g dose and a second, smaller dose.She was discharged to psychiatric care.
Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004
Authors: Luc Bauchet, Hélène Mathieu-Daudé, Pascale Fabbro-Peray, Valérie Rigau, Michel Fabbro, Olivier Chinot, Loreleï Pallusseau, Charlotte Carnin, Karl Lainé, Aline Schlama, Agnes Thiebaut, Maria Cristina Patru, Fabienne Bauchet, Martine Lionnet, Michel Wager, Thierry Faillot, Luc Taillandier, Dominique Figarella-Branger, Laurent Capelle, Hugues Loiseau, Didier Frappaz, Chantal Campello, Christine Kerr, Hugues Duffau, Monique Reme-Saumon, Brigitte Trétarre, Jean-Pierre Daures, Dominique Henin, François Labrousse, Philippe Menei, Jérome Honnorat
Journal: Neuro-Oncology (2010)

This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/− adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266–314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ(n=224): 476 (441–506), biopsy + RT-TMZ(n=90): 329 (301–413), RS + RT(n=147): 363 (331–431), biopsy + RT(n=89): 178 (153–237), RS + CT(n=61): 245 (190–361), biopsy + CT(n=96): 244 (198–280), and biopsy only(n=118): 55 (46–71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.
Airway epithelial hemoglobin β regulates ciliary endothelial NOS
Authors: Nadzeya Marozkina, Giovanni Piedimonte, Lesly Cottrell, Vinod Jyothikumar, Amasi Periasamy, Khalequz Zaman, Adam Straub, Scott Randell, Benjamin Gaston
Journal: European Respiratory Journal (2013)

Introduction : Patients with primary ciliary dyskinesia (PCD) and asthmatic obesity can have airway inflammation but low FENO. Endothelial hemoglobin (Hb) α and metHb reductase (MetHbR) expression (Straub,  Nature , 2012) regulate eNOS: Hb-Fe 2+/ eNOS forms inert NO 3  - , while Fe 3+ /eNOS form active NO and S-nitrosothiols (SNOs). Thus, we studied whether airway ciliary eNOS was regulated by Hb and MetHbR.   Methods . Hb, MetHbR, eNOS, and TRPV 4 were visualized by confocal microscopy (CFM) and immunofluorescence (IF); Ca 2+  flux by CFM; and NADH autofluorescence by 2-photon. SNOs, NO 2  -  and NO 3  -  assays used reductive chemiluminescence. Human pseudostrutified airway epithelial cells at air-liquid interface (HAE-ALI) were exposed to airway cyclic compressive stress (CCS). Breath condensate (BC) was from 65 school children.   Results.  TRPV4 was in cilia, eNOS and Hb β (but not α) were at the base of cilia; MetHbR was cytosolic. Both CCS and Ca 2+  ionophore caused Ca 2+  flux into HAE through TRPV4, activating eNOS to triple SNO levels; this was prevented by NOS inhibition (p  3 -, not NO or SNO). Obese asthmatic children had higher BC NO 3  -  (mean, 10.6 μM) than non-obese asthmatics (7.6), or than obese (6.0) or non-obese (2.5) controls.   Conclusions.  HAE stretch allows Ca 2+  entry, activating ciliary eNOS. Whether eNOS produces bioactive NO and SNOs or inert NO 3  -  depends on MetHbR: high glucose favors Hb β reduction/NO 3  - . Thus, asthmatics with high glucose will oxidize airway NO. Decreased exercise should also lead to decreased CCS in vivo, decreasing eNOS activity. This may explain low FENO and high airway NO 3  -  in obese asthma patients, as well as low FENO in PCD.
Combining Enzalutamide with Abiraterone, Prednisone, and Androgen Deprivation Therapy in the STAMPEDE Trial
Authors: Gerhardt Attard, Matthew R. Sydes, Malcolm D. Mason, Noel W. Clarke, Daniel Aebersold, Johann S. de Bono, David P. Dearnaley, Chris C. Parker, Alastair W.S. Ritchie, J. Martin Russell, George Thalmann, Estelle Cassoly, Robin Millman, David Matheson, Francesca Schiavone, Melissa R. Spears, Mahesh K.B. Parmar, Nicholas D. James
Journal: European Urology (2014)

There are compelling reasons to study the addition of both enzalutamide and abiraterone, in combination, to standard-of-care for hormone-naïve prostate cancer. Through a protocol amendment, this will be assessed in the STAMPEDE trial, with overall survival as primary outcome measure.
Protection by Corynebacterium granulosum Against Radiation-Induced Enhancement of Artificial Pulmonary Metastases of a Murine Fibrosarcoma2
Authors: L. Milas, Nancy Hunter, I. Bašić, H. Rodney Withers
Journal: JNCI Journal of the National Cancer Institute (1974)

Intraperitoneal treatment of C3Hf/Bu mice with killed Corynebacterium granulosum bacteria before intravenous inoculation of cells from a syngeneic fibrosarcoma greatly reduced the number of metastatic nodules in the lung. In contrast, the number of pulmonary metastases was significantly increased in mice previously given whole-body irradiation of 200–600 rads of γ-rays. Pretreatment of animals with C. granulosum before irradiation not only abolished this effect but also produced a response equal to that in mice treated with the immunostimulant alone. C. granulosum protected the mice against radiationinduced enhancement of pulmonary metastases if given within 2, but not at 4, weeks before irradiation. However, if mice were first irradiated and then, 1 or 2 days later, treated with C. granulosum, the radiation effect on the formation of pulmonary metastases was not influenced.
Mortality and Cardiovascular Risk Across the Ankle-Arm Index Spectrum
Authors: Ann M. O’Hare, Ronit Katz, Michael G. Shlipak, Mary Cushman, Anne B. Newman
Journal: Circulation (2006)

A low ankle-arm index (AAI) is a strong predictor of mortality and cardiovascular events. A high AAI also appears to be associated with higher mortality risk in select populations. However, mortality and cardiovascular risk across the AAI spectrum have not been described in a more broadly defined population.We examined total and cardiovascular mortality and cardiovascular events across the AAI spectrum among 5748 participants in the Cardiovascular Health Study (CHS). The mean age of the sample population was 73+/-6 years, and the sample included 3289 women (57%) and 883 blacks (15%). The median duration of follow-up was 11.1 (0.1 to 12) years for mortality and 9.6 (0.1 to 12.1) years for cardiovascular events. There were 2311 deaths (953 of which were cardiovascular) and 1491 cardiovascular events during follow-up. After adjustment for potential confounders, AAI measurements < or =0.60 (hazard ratio [HR] 1.82, 95% CI 1.42 to 2.32), 0.61 to 0.7 (HR 2.08, 95% CI 1.61 to 2.69), 0.71 to 0.8 (HR 1.80, 95% CI 1.44 to 2.26), 0.81 to 0.9 (HR 1.73 95% CI 1.43 to 2.11), 0.91 to 1.0 (HR 1.40, 95% CI 1.20 to 1.63), and >1.40 (HR 1.57, 95% CI 1.07 to 2.31) were associated with higher mortality risk from all causes compared with the referent group (AAI 1.11 to 1.20). The pattern was similar for cardiovascular mortality. For cardiovascular events, risk was higher at all AAI levels <1 but not for AAI levels >1.4 (HR 1.00, 95% CI 0.57 to 1.74). The association of a high AAI with mortality was stronger in men than in women and in younger than in older cohort members.In a cohort of community-dwelling elders, mortality risk was higher than the referent category of 1.11 to 1.2 among participants with AAI values above the traditional cutpoint of 0.9 (ie, 0.91 to 1.0 and >1.4), and the specific association of AAI with mortality varied by age and gender.
The Heart: Structure in Health and Disease.
Authors: P. D RIDLEY
Journal: Cardiovascular Research (1993)

The Heart: Structure in Health and Disease. Get access PAUL D RIDLEY PAUL D RIDLEY Teaching Research Bristol, UK By R H Anderson and A E Becker. (Pp 296; $US206.50.) New York: Raven Press, 1992. ISBN 0-397-44719-1. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 7, July 1993, Pages 1384–1385, https://doi.org/10.1093/cvr/27.7.1384a Published: 01 July 1993
The Role of Clinical Suspicion in Evaluating a New Diagnostic Test for Active Tuberculosis
Authors: Antonino Catanzaro, Sharon Perry, Jill E. Clarridge, Sherry Dunbar, Sheila Goodnight-White, Philip A. LoBue, Christopher Peter, Gaby E. Pfyffer, Marcelino F. Sierra, Rainer Weber, Gail Woods, Greg Mathews, Vivian Jonas, Katie Smith, Phyllis Della-Latta
Journal: JAMA (2000)

ContextIn laboratory trials, nucleic acid amplification tests for the diagnosis of tuberculosis (TB) are more accurate than acid-fast bacilli (AFB) smear microscopy and are faster than culture. The impact of these tests on clinical diagnosis is not known.ObjectiveTo assess the performance of a nucleic acid amplification test, the enhanced Mycobacterium tuberculosis Direct (E-MTD) test, against a uniform clinical standard stratified by level of clinical suspicion.DesignProspective multicenter trial conducted between February and December 1996, documenting the clinical suspicion of TB at enrollment and using final comprehensive diagnosis as the criterion standard.SettingSix urban medical centers and 1 public health TB clinic.PatientsA total of 338 patients with symptoms and signs consistent with active pulmonary TB and complete clinical diagnosis were stratified by the clinical investigators to be at low (≤25%), intermediate (26%-75%), or high (>75%) relative risk of having TB.Main Outcome MeasuresSensitivity, specificity, and positive and negative predictive values of the E-MTD test in clinical suspicion of groups with low (n = 224); intermediate (n = 68); and high (n = 46) clinical suspicion of TB.ResultsBased on comprehensive clinical diagnosis, sensitivity of the E-MTD test was 83%, 75%, and 87% for low, intermediate, and high clinical suspicion of TB, respectively, and corresponding specificity was 97%, 100%, and 100% (P = .25). Positive predictive value of the E-MTD test was 59% (low), 100% (intermediate), and 100% (high) compared with 36% (low), 30% (intermediate), and 94% (high) for AFB smear. Corresponding negative predictive values were 99%, 91%, and 91% (E-MTD test) vs 96%, 71%, and 37% (AFB smear).ConclusionsFor complex diagnostic problems like TB, clinical risk assessments can provide important information regarding predictive values more likely to be experienced in clinical practice. For this series, a clincial suspicion of TB was helpful in targeting areas of the clinical spectrum in which nucleic acid amplification tests can make an important contribution.