tbuckley/cabot-search huggingface dataset:
STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS
Authors: Lester S. King
Journal: The Journal of Experimental Medicine (1942)

50 per cent glycerine injected intraperitoneally, intramuscularly, or intravenously, greatly enhances the activity of equine encephalomyelitis virus injected intramuscularly, increasing its virulence up to 100-fold. The same effect is produced by very concentrated sodium chloride. The result appears due to dehydration of the nervous system, suddenly produced. Gradual withdrawal of body fluids, produced by depriving animals of drinking water, results in sharp concentration of the blood, equal to that produced by glycerine or salt. But such deprivation of water alone does not result in significant dehydration of the brain, nor does it have any effect on virus action. The facilitation effect is not produced by drastic procedures involving shifts of electrolytes without loss of total water from the brain. Glycerine has no facilitating action when the virus is administered intranasally or intraocularly, suggesting a fundamental difference in pathogenesis between these routes and the intramuscular.
Activation of the Interleukin-6/STAT3 Antiapoptotic Pathway in Esophageal Cells by Bile Acids and Low pH: Relevance to Barrett's Esophagus
Authors: Katerina Dvorak, Melissa Chavarria, Claire M. Payne, Lois Ramsey, Cara Crowley-Weber, Barbora Dvorakova, Bohuslav Dvorak, Harris Bernstein, Hana Holubec, Richard E. Sampliner, Carol Bernstein, Anil Prasad, Sylvan B. Green, Harinder Garewal
Journal: Clinical Cancer Research (2007)

Abstract Objectives: The molecular factors contributing to the development of Barrett's esophagus (BE) are unclear. Our previous studies showed that BE tissues secrete interleukin-6 (IL-6) and express proteins associated with IL-6 signaling, including IL-6 receptor, activated signal transducer and activators of transcription 3 (STAT3), and antiapoptotic proteins Bcl-xL and Mcl-1. Here, we test the hypothesis that bile acids and gastric acids, two components of refluxate associated with gastresophageal reflux disease, activate the IL-6/STAT3 pathway. Materials and Methods: Immunohistochemistry was used to assess levels of phosphorylated STAT3 in esophageal tissue samples from BE patients with different grades of dysplasia. Seg-1 esophageal adenocarcinoma cells were evaluated for STAT3 activation and IL-6 and Bcl-xL expression by molecular biology techniques, including Western blot, reverse transcription–PCR, and ELISA after exposure to control media (pH 7.4), media supplemented with a 0.1 mmol/L bile acid cocktail with media at pH 4 or media at pH 4 with bile acid cocktail. Results: Immunohistochemical analysis showed that activated, phosphorylated STAT3 is expressed in nuclei of dysplastic BE and cancer tissues. Treatment of Seg-1 cells with media containing bile acid cocktail and acidified to pH 4 resulted in increased activation of STAT3, IL-6 secretion, and increased expression of Bcl-xL. Inhibition of the STAT3 pathway using STAT3 small interfering RNA or Janus-activated kinase inhibitor resulted in increased apoptosis. Conclusions: The IL-6/STAT3 antiapoptotic pathway is induced by short exposure to bile acid cocktail and low pH. This alteration, if persistent in vivo, may underlie the development of dysplastic BE and tumor progression.
Migraine and cognitive decline among women: prospective cohort study
Authors: P. M. Rist, J. H. Kang, J. E. Buring, M. M. Glymour, F. Grodstein, T. Kurth
Journal: BMJ (2012)

<b>Objective</b> To evaluate the association between migraine and cognitive decline among women. <b>Design</b> Prospective cohort study. <b>Setting</b> Women’s Health Study, United States. <b>Participants</b> 6349 women aged 65 or older enrolled in the Women’s Health Study who provided information about migraine status at baseline and participated in cognitive testing during follow-up. Participants were classified into four groups: no history of migraine, migraine with aura, migraine without aura, and past history of migraine (reports of migraine history but no migraine in the year prior to baseline). <b>Main outcome measures</b> Cognitive testing was carried out at two year intervals up to three times using the telephone interview for cognitive status, immediate and delayed recall trials of the east Boston memory test, delayed recall trial of the telephone interview for cognitive status 10 word list, and a category fluency test. All tests were combined into a global cognitive score, and tests assessing verbal memory were combined to create a verbal memory score. <b>Results</b> Of the 6349 women, 853 (13.4%) reported any migraine; of these, 195 (22.9%) reported migraine with aura, 248 (29.1%) migraine without aura, and 410 (48.1%) a past history of migraine. Compared with women with no history of migraine, those who experienced migraine with or without aura or had a past history of migraine did not have significantly different rates of cognitive decline in any of the cognitive scores: values for the rate of change of the global cognitive score between baseline and the last observation ranged from −0.01 (SE 0.04) for past history of migraine to 0.08 (SE 0.04) for migraine with aura when compared with women without any history of migraine. Women who experienced migraine were also not at increased risk of substantial cognitive decline (worst 10% of the distribution of decline). When compared with women without a history of migraine, the relative risks for the global score ranged from 0.77 (95% confidence interval 0.46 to 1.28) for women with migraine without aura to 1.17 (0.84 to 1.63) for women with a past history of migraine. <b>Conclusion</b> In this prospective cohort of women, migraine status was not associated with faster rates of cognitive decline.
Adult Niemann‐Pick disease masquerading as sea blue histiocyte syndrome: Report of a case confirmed by lipid analysis and enzyme assays
Authors: Steve Landas, Kathy Foucar, Gloria N. Sando, Ralph Ellefson, Henry E. Hamilton
Journal: American Journal of Hematology (1985)

Abstract We present the clinical, pathologic, and metabolic findings of an adult woman with debilitating coronary artery disease and hepatosplenomegaly who was discovered to have multiorgan infiltration by sea blue histiocytes. A diagnosis of sea blue histiocyte (SBH) syndrome was made and no further workup performed. The patient suffered from progressive heart failure and sepsis following coronary artery bypass surgery and died 9 months after presentation. Tissues examined at autopsy showed pronounced infiltrates of both granular sea blue histiocytes and foamy, vacuolated histiocytes, which were morphologically compatible with Niemann‐Pick cells. Ultra‐structural examination of these cells revealed lamellar myelin‐like figures as described in Niemann‐Pick (N‐P) disease. Fibroblast enzyme assay studies and liver lipid analyses performed after the patient's death revealed pronounced sphingomyelinase deficiency and a lipid profile diagnostic of N‐P disease, type B. This case adds further support to the claim that some cases of apparent SBH syndrome actually represent a type of N‐P disease.
Bronchodilators in COPD.
Authors: J C Yernault, A Noseda
Journal: Thorax (1994)

aggerated sensitivity to LTC4 has been ob- served to be a characteristic of s-salbutamol in allergic animals.7There can be no doubt that allergic hyperreactivity in the guinea pig is spasmogen selective, with LTC4, LTE4, and histamine being sensitive indicators of this phenomenon.However, following protracted (six days) exposure to salbutamol (1 mg/kg/ day) there is a divergence of changed re- sponsiveness such that it might be concluded from studies using LTC4 or LTE4 that airway responsiveness had increased whereas, at the same time and in the same anirnal, reduced responsiveness to histamine would favour a contrary conclusion.Hence, before ca- tegorising changes in airway responsiveness due to sympathomimetics as being small in asthmatic subjects, it would be prudent to examine a wider range of test spasmogens.When first investigated by use of sophisticated recording techniques, it was concluded that allergic airway hyperreactivity did not occur in the guinea pig.8By giving consideration to alternative test spasmogens it is now possible to demonstrate substantial increased airway responsiveness during a modest allergic reaction in this species.3Furthermore, it is possible to define circumstances whereby sus- tained exposure to sympathomimetics heightens susceptibility to certain allergic mediators so that the response to a low dose of antigen is transformed from a source of mild dis- comfort to sudden death.In the absence of experimental data, it cannot be presumed that this phenomenon cannot occur in asthma.
Interactions of Viruses with Dendritic Cells: A Double-edged Sword
Authors: Nina Bhardwaj
Journal: The Journal of Experimental Medicine (1997)

Diverse mechanisms are used by viruses to inhibit, block, or evade the immune response (see review in reference ([1][1])). These include reduced expression of critical antigenic epitopes (e.g., EBV in latency), genetic variation of class I–restricted CTL epitopes (HIV-1), clonal exhaustion of CTLs
Detection of Cerebrospinal Fluid Leaks by Intrathecal Contrast-Enhanced Magnetic Resonance Myelography
Authors: Athina Papadopoulou, Frank-Johannes Ahlhelm, Stephan Ulmer, Ludwig Kappos, Till Sprenger
Journal: JAMA Neurology (2013)

A 70-year-old woman had double vision, nausea, neck pain, and acute bilateral hypacusis. The neurological examination showed nerve VI palsy on the right. There was no history of trauma. Brain magnetic resonance (MR) imaging was indicative of intracranial hypotension, with diffuse pachymeningeal thickening, strong dural enhancement, and frontoparietal subdural hygromas. A radioisotope cisternography, performed in the search for a potential spinal cerebrospinal fluid (CSF) leak, was inconclusive. Thus, intrathecal gadolinium-enhanced MR myelography was considered as a possible alternative. Before intrathecal gadolinium administration, an MR image of the spinal cord showed a small perineural cyst at the level of L2 on the right but no evidence of a CSF leakage. The intrathecal gadolinium-enhanced MR myelography provided clear-cut evidence of dural leaks along the right L2 and L3 nerve roots (Figure). According to these findings, targeted epidural blood patching was performed and the patient’s symptoms gradually improved during the following month. At 1-year follow-up, she was asymptomatic.
Efficacy of Quinidine in High-Risk Patients With Brugada Syndrome
Authors: Bernard Belhassen, Aharon Glick, Sami Viskin
Journal: Circulation (2004)

Automatic implantable cardioverter-defibrillator therapy is considered the only effective treatment for high-risk patients with Brugada syndrome. Quinidine depresses I(to) current, which may play an important role in the arrhythmogenesis of this disease.The effects of quinidine bisulfate (mean dose, 1483+/-240 mg) on the prevention of inducible and spontaneous ventricular fibrillation (VF) were prospectively evaluated in 25 patients (24 men, 1 woman; age, 19 to 80 years) with Brugada syndrome. There were 15 symptomatic patients (including 7 cardiac arrest survivors and 7 patients with unexplained syncope) and 10 asymptomatic patients. All 25 patients had inducible VF at baseline electrophysiological study. Quinidine prevented VF induction in 22 of the 25 patients (88%). After a follow-up period of 6 months to 22.2 years, all patients are alive. Nineteen patients were treated with quinidine for 6 to 219 months (mean+/-SD, 56+/-67 months). None had an arrhythmic event, although 2 had non-arrhythmia-related syncope. Administration of quinidine was associated with a 36% incidence of side effects that resolved after drug discontinuation.Quinidine effectively prevents VF induction in patients with Brugada syndrome. Our data suggest that quinidine also suppresses spontaneous arrhythmias and could prove to be a safe alternative to automatic implantable cardioverter-defibrillator therapy for a substantial proportion of patients with Brugada syndrome. Randomized studies comparing these two therapies seem warranted.
Cardiovascular Risk of High- Versus Moderate-Intensity Aerobic Exercise in Coronary Heart Disease Patients
Authors: Øivind Rognmo, Trine Moholdt, Hilde Bakken, Torstein Hole, Per Mølstad, Nils Erling Myhr, Jostein Grimsmo, Ulrik Wisløff
Journal: Circulation (2012)

Background— Exercise performed at higher relative intensities has been found to elicit a greater increase in aerobic capacity and greater cardioprotective effects than exercise at moderate intensities. An inverse association has also been detected between the relative intensity of physical activity and the risk of developing coronary heart disease, independent of the total volume of physical activity. Despite that higher levels of physical activity are effective in reducing cardiovascular events, it is also advocated that vigorous exercise could acutely and transiently increase the risk of sudden cardiac death and myocardial infarction in susceptible persons. This issue may affect cardiac rehabilitation. Methods and Results— We examined the risk of cardiovascular events during organized high-intensity interval exercise training and moderate-intensity training among 4846 patients with coronary heart disease in 3 Norwegian cardiac rehabilitation centers. In a total of 175 820 exercise training hours during which all patients performed both types of training, we found 1 fatal cardiac arrest during moderate-intensity exercise (129 456 exercise hours) and 2 nonfatal cardiac arrests during high-intensity interval exercise (46 364 exercise hours). There were no myocardial infarctions in the data material. Because the number of high-intensity training hours was 36% of the number of moderate-intensity hours, the rates of complications to the number of patient-exercise hours were 1 per 129 456 hours of moderate-intensity exercise and 1 per 23 182 hours of high-intensity exercise. Conclusions— The results of the current study indicate that the risk of a cardiovascular event is low after both high-intensity exercise and moderate-intensity exercise in a cardiovascular rehabilitation setting. Considering the significant cardiovascular adaptations associated with high-intensity exercise, such exercise should be considered among patients with coronary heart disease.
Marrow Transplantation for the Treatment of Chronic Myelogenous Leukemia
Authors: E D Thomas, R A Clift, A Fefer, F R Appelbaum, P Beatty, W I Bensinger, C D Buckner, M A Cheever, H J Deeg, K Doney
Journal: Annals of Internal Medicine (1986)

One hundred ninety-eight patients with chronic myelogenous leukemia received marrow transplants after intensive chemotherapy and total body irradiation. Multivariate analysis showed disease status at time of transplantation to be the most powerful predictor of survival. The probability of long-term survival for allogeneic graft recipients was 49% for 67 patients in the first chronic phase, 58% for 12 in the second chronic phase, 15% for 46 in the accelerated phase, and 14% for 42 in the blastic phase. The major cause of death was interstitial pneumonia for patients in the chronic phase, and relapse for those in the blastic or accelerated phases. Factors favoring survival were early transplantation, age less than 30 years, and absence of severe graft-versus-host disease. Splenectomy or spleen size did not influence survival. For recipients of syngeneic grafts survival probability was 87% for 16 patients in the chronic phase, 27% for 7 in the accelerated phase, and 12% for 8 in the blastic phase. Of the 198 patients, 71 are alive without Philadelphia chromosomes 1 to 9 years after receiving their graft. All but 4 long-term disease-free survivors have Karnofsky performance scores of 80% or better.
The contrasting roles of PPARδ and PPARγ in regulating the metabolic switch between oxidation and storage of fats in white adipose tissue
Authors: Lee D Roberts, Andrew J Murray, David Menassa, Tom Ashmore, Andrew W Nicholls, Julian L Griffin
Journal: Genome biology (2011)

The nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and peroxisome proliferator-activated receptor δ (PPARδ) play central roles in regulating metabolism in adipose tissue, as well as being targets for the treatment of insulin resistance. While the role of PPARγ in regulating insulin sensitivity has been well defined, research into PPARδ has been limited until recently due to a scarcity of selective PPARδ agonists. The metabolic effects of PPARγ and PPARδ activation have been examined in vivo in white adipose tissue from ob/ob mice and in vitro in cultured 3T3-L1 adipocytes using 1H nuclear magnetic resonance spectroscopy and mass spectrometry metabolomics to understand the receptors' contrasting roles. These steady state measurements were supplemented with 13C-stable isotope substrate labeling to assess fluxes, in addition to respirometry and transcriptomic microarray analysis. The metabolic effects of the receptors were readily distinguished, with PPARγ activation characterized by increased fat storage, synthesis and elongation, while PPARδ activation caused increased fatty acid β-oxidation, tricarboxylic acid cycle rate and oxidation of extracellular branch chain amino acids. Stimulated glycolysis and increased fatty acid desaturation were common pathways for the agonists. PPARγ and PPARδ restore insulin sensitivity through varying mechanisms. PPARδ activation increases total oxidative metabolism in white adipose tissue, a tissue not traditionally thought of as oxidative. However, the increased metabolism of branch chain amino acids may provide a mechanism for muscle atrophy, which has been linked to activation of this nuclear receptor. PPARδ has a role as an anti-obesity target and as an anti-diabetic, and hence may target both the cause and consequences of dyslipidemia.
Levels of description and conflated doctrines
Authors: John A. Bullinaria
Journal: Behavioral and Brain Sciences (1999)

It seems that I often say things that might mistakenly be thought to identify me as an adherent of the radical neuron doctrine. I take the opportunity to explain my position more clearly and argue that many apparent conflations of the radical and trivial neuron doctrines are merely the result of misunderstanding what is meant when neuroscientists talk about the relations between different levels of description. It follows that there may be considerably fewer followers of the radical doctrine than Gold &amp; Stoljar suggest.
Transplantation of Nanoparticle Transfected Skeletal Myoblasts Overexpressing Vascular Endothelial Growth Factor-165 for Cardiac Repair
Authors: Lei Ye, Husnain Kh Haider, RuSan Tan, WeeChi Toh, Peter K. Law, WeeBeng Tan, LiPing Su, Wei Zhang, RuoWen Ge, Yong Zhang, YeanTeng Lim, Eugene K.W. Sim
Journal: Circulation (2007)

We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF165) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium.Based on optimized transfection procedure using enhanced green fluorescent protein (pEGFP), HSM were transfected with plasmid-hVEGF165 (phVEGF165) carried by PEI (PEI-phVEGF165) nanoparticles. The transfected HSM were characterized for transfection and expression of hVEGF165 in vitro and transplanted into rat heart model of acute myocardial infarction (AMI): group-1=DMEM injection, group-2= HSM transplantation, group-3= PEI-phVEGF165-transfected HSM (PEI-phVEGF165 myoblast) transplantation. A total of 48 rats received cyclosporine injection from 3 days before and until 4 weeks after cell transplantation. Echocardiography was performed to assess the heart function. Animals were sacrificed for molecular and histological studies on the heart tissue at 4 weeks after treatment. Based on optimized transfection conditions, transfected HSM expressed hVEGF165 for 18 days with >90% cell viability in vitro. Apoptotic index was reduced in group-2 and group-3 as compared with group-1. Blood vessel density (x400) by immunostaining for PECAM-1 in group-3 was significantly higher (P=0.043 for both) as compared with group-1 and group-2 at 4 weeks. Regional blood flow (ml/min/g) in the left ventricular anterior wall was higher in group-3 (P=0.043 for both) as compared with group-1 and group-2. Improved ejection fraction was achieved in group-3 (58.44+/-4.92%) as compared with group-1 (P=0.004).PEI nanoparticle mediated hVEGF165 gene transfer into HSM is feasible and safe. It may serve as a novel and efficient alternative for angiomyogenesis in cardiac repair.
Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells
Authors: Christoph Becker, Stefan Wirtz, Manfred Blessing, Jaana Pirhonen, Dennis Strand, Oliver Bechthold, Julia Frick, Peter R. Galle, Ingo Autenrieth, Markus F. Neurath
Journal: Journal of Clinical Investigation (2003)

IL-12 p40–related cytokines such as IL-12 p35/p40 heterodimer and IL-23 (p19/p40) are potent regulators of adaptive immune responses. Little is known, however, about the transcriptional regulation of the p40 gene in vivo. In an attempt toward this goal, we have generated transgenic mice expressing firefly luciferase under the control of the IL-12 p40 promoter. High constitutive transgene expression was found in the small intestine only, whereas little reporter gene activity was observed in other tissues. Within the small bowel, constitutive promoter activity was restricted to the terminal ileum and associated with high expression of p40 mRNA as well as p40 and IL-23 p19/p40 proteins. The cells constitutively producing IL-12 p40 were identified as CD8α and CD11b double-negative CD11c+ lamina propria dendritic cells (LPDCs) that represent a major cell population in the lamina propria of the small intestine, but not in the colon. FISH directly demonstrated the uptake of bacteria by a subset of LPDCs in the terminal ileum that was associated with p40 expression. Furthermore, little or no p40 protein expression in LPDCs was found in the terminal ileum of germfree mice, indicating a key role of the intestinal flora for constitutive p40 expression. In addition, analysis of transgenic mice with a mutated NF-κB target site in the p40 promoter showed a critical role of NF-κB for constitutive transgene expression. Our data reveal important functional differences between the mucosal immune systems of the small and large bowel in healthy mice and suggest that the high bacterial load in the terminal ileum activates p40 gene transcription in LPDCs through NF-κB. These data suggest a predisposition of the terminal ileum to develop chronic inflammatory responses through IL-23 and thus may provide a molecular explanation for the preferential clinical manifestation of Crohn disease in this part of the gut.
ETIOLOGY OF OROYA FEVER
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1926)

Experiments are reported in which Bartonella bacilliformis was transmitted from infected to normal rhesus monkeys by the bite of the tick, Dermacentor andersoni. A long period of feeding, both on the infected animal and on the normal animal subjected to infection, was required in order to secure positive results. The infection transmitted by the ticks was mild, but definite, as shown by the recovery of Bartonella bacilliformis from the lymph nodes and blood.
Incidence, Predictors, Treatment, and Long-Term Prognosis of Patients With Restenosis After Drug-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease
Authors: Jong-Young Lee, Duk-Woo Park, Young-Hak Kim, Sung-Cheol Yun, Won-Jang Kim, Soo-Jin Kang, Seung-Whan Lee, Cheol-Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2011)