tbuckley/cabot-search huggingface dataset:
Sympathetic control of major coronary artery diameter in the dog.
Authors: M Gerová, E Barta, J Gero
Journal: Circulation Research (1979)

The diameter of a major coronary artery, the ramus interventricularis ventralis (RIV), was measured in dogs with arrested hearts perfused by an extracorporeal circulation. The resting diastolic diameter was 1.78 +/- 0.07 mm (mean +/- SE) at a diastolic pressure of 74.2 +/- 3.4 mm Hg. Bilateral supramaximal stimulation of fibers leaving the cranial pole of the stellate ganglion decreased the diameter by 71.2 +/- 8.9 micrometer, i.e., 4.0 +/- 0.5% of the resting diameter. Stimulation of the left stellate ganglion contributed 59.8 +/- 5.7% of the maximum response; that of the right contributed 40.3 +/- 5.5%. Stimulation of the thoracic ganglia (T2-4) resulted in a 1.2 +/- 0.4% decrease in coronary vessel diameter. RIV failed to respond to bilateral caudal cervical ganglion stimulation. After iv administration of phentolamine, 1-2 mg/kg, no response to sympathetic stimulation could be elicited. Therefore, it appears that alpha-receptors are activated by the release of the sympathetic neurotransmitter to sympathetic stimulation and that beta-receptors are not involved in the response of RIV to sympathetic stimulation.
Whole-Genome Analysis of Sporadic Amyotrophic Lateral Sclerosis
Authors: Travis Dunckley, Matthew J. Huentelman, David W. Craig, John V. Pearson, Szabolcs Szelinger, Keta Joshipura, Rebecca F. Halperin, Chelsea Stamper, Kendall R. Jensen, David Letizia, Sharon E. Hesterlee, Alan Pestronk, Todd Levine, Tulio Bertorini, Michael C. Graves, Tahseen Mozaffar, Carlayne E. Jackson, Peter Bosch, April McVey, Arthur Dick, Richard Barohn, Catherine Lomen-Hoerth, Jeffrey Rosenfeld, Daniel T. O'Connor, Kuixing Zhang, Richard Crook, Henrik Ryberg, Michael Hutton, Jonathan Katz, Ericka P. Simpson, Hiroshi Mitsumoto, Robert Bowser, Robert G. Miller, Stanley H. Appel, Dietrich A. Stephan
Journal: New England Journal of Medicine (2007)

Approximately 90% of persons with amyotrophic lateral sclerosis (ALS) have the sporadic form, which may be caused by the interaction of multiple environmental factors and previously unknown genes.We performed a genomewide association analysis using 766,955 single-nucleotide polymorphisms (SNPs) found in 386 white patients with sporadic ALS and 542 neurologically normal white controls (the discovery series). Associations of SNPs with sporadic ALS were confirmed in two independent replication populations: replication series 1, with 766 case patients with the disease and 750 neurologically normal controls, and replication series 2, with 135 case patients and 275 controls.We identified 10 genetic loci that are significantly associated (P<0.05) with sporadic ALS in three independent series of case patients and controls and an additional 41 loci that had significant associations in two of the three series. The most significant association with disease in white case patients as compared with controls was found for a SNP near an uncharacterized gene known as FLJ10986 (P=3.0x10(-4); odds ratio for having the genotype in patients vs. controls, 1.35; 95% confidence interval, 1.13 to 1.62). The FLJ10986 protein was found to be expressed in the spinal cord and cerebrospinal fluid of patients and of controls. Specific SNPs seem to be associated with sex, age at onset, and site of onset of sporadic ALS.Variants of FLJ10986 may confer susceptibility to sporadic ALS. FLJ10986 and 50 other candidate loci warrant further investigation for their potential role in conferring susceptibility to the disease.
Myocardial Protection at a Crossroads
Authors: Roberto Bolli, Lance Becker, Garrett Gross, Robert Mentzer, David Balshaw, David A. Lathrop
Journal: Circulation Research (2004)

Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery).
Urticarial vasculitis associated with a monoclonal IgM gammopathy: Schnitzler's syndrome
Authors: L. BORRADORI, M. RYBOJAD, A. PUISSANT, A. DALLOT, O. VEROLA, P. MOREL
Journal: British Journal of Dermatology (1990)

Journal Article Urticarial vasculitis associated with a monoclonal IgM gammopathy: Schnitzler's syndrome Get access L. BORRADORI, L. BORRADORI Dermatology Clinic, Hôpital Saint Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar M. RYBOJAD, M. RYBOJAD Dermatology Clinic, Hôpital Saint Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar A. PUISSANT, A. PUISSANT Dermatology Clinic, Hôpital Saint Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar A. DALLOT, A. DALLOT Dermatology Clinic, Hôpital Saint Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar O. VEROLA, O. VEROLA Central Pathology Laboratory, Hôpital Saint Louis, Paris, France Search for other works by this author on: Oxford Academic Google Scholar P. MOREL P. MOREL Dermatology Clinic, Hôpital Saint Louis, Paris, France Dr P.Morel, Clinique Dermatologique, Hôpital Saint Louis, I Avenue Claude Vellefaux, 75010 Paris, France. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 1, 1 July 1990, Pages 113–118, https://doi.org/10.1111/j.1365-2133.1990.tb01831.x Published: 01 July 1990
Dendritic cell maturation by innate lymphocytes
Authors: Christian Münz, Ralph M. Steinman, Shin-ichiro Fujii
Journal: The Journal of Experimental Medicine (2005)

Pathogen recognition by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation and the initiation of adaptive immunity. Recent studies have shown that innate lymphocytes--natural killer (NK), natural killer T (NKT), and gammadelta T cells--also trigger DC maturation. This interaction in turn expands and activates innate lymphocytes and initiates adaptive T cell immunity. Here, we comment on the evidence that these pathways are TLR independent and have the potential to respond to infection, malignancy, and immunotherapy.
Hepatic low-density lipoprotein receptor–related protein deficiency in mice increases atherosclerosis independent of plasma cholesterol
Authors: Sonia M. S. Espirito Santo, Nuno M. M. Pires, Lianne S. M. Boesten, Gery Gerritsen, Niels Bovenschen, Ko Willems van Dijk, J. Wouter Jukema, Hans M. G. Princen, André Bensadoun, Wei-Ping Li, Joachim Herz, Louis M. Havekes, Bart J. M. van Vlijmen
Journal: Blood (2004)
Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome
Authors: Nancy J. Butcher, Tim-Rasmus Kiehl, Lili-Naz Hazrati, Eva W. C. Chow, Ekaterina Rogaeva, Anthony E. Lang, Anne S. Bassett
Journal: JAMA Neurology (2013)

Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition.To evaluate a possible association between 22q11.2 deletions and PD.An observational study of the occurrence of PD in the world's largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1-68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder.A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0-178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein-positive Lewy bodies were present in the expected distribution in 2 cases but absent in another.These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological presentation reminiscent of LRRK2-associated PD neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS should be considered for genetic testing, and those with a known 22q11.2 deletion should be monitored for the development of parkinsonian symptoms. Molecular studies of the implicated genes, including DGCR8, may help shed light on the underlying pathophysiology of PD in 22q11.2DS and idiopathic PD.
Legislation on research involving patients who are (temporarily) unable to give informed consent: differences between European countries
Authors: Michael A. Kuiper, Denise P. Veelo, Peter E. Spronk, Marcus J. Schultz
Journal: Intensive Care Medicine (2007)

Sir: Recently Ciroldi et al. reported on the ability of family members to predict patient's consent to critical care research [1]. They showed that family members designated to serve as surrogate decision makers fail to accurately consent to research in one-third to one-half of cases.
Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis
Authors: E Csinady, V H J van der Velden, R Joas, S Fischer, J F de Vries, H B Beverloo, M König, U Pötschger, J J M van Dongen, G Mann, O A Haas, E R Panzer-Grümayer
Journal: Leukemia (2009)
Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark
Authors: M. Frisch, B. V Pedersen, R. E Andersson
Journal: BMJ (2009)

<b>Objective</b> To determine whether the repeatedly observed low risk of ulcerative colitis after appendicectomy is related to the appendicectomy itself or the underlying morbidity, notably appendicitis or mesenteric lymphadenitis. <b>Design</b> Nationwide cohort studies. <b>Setting</b> Sweden and Denmark. <b>Participants</b> 709 353 Swedish (1964-2004) and Danish (1977-2004) patients who had undergone appendicectomy were followed up for subsequent ulcerative colitis. The impact of appendicectomy on risk was also studied in 224 483 people whose parents or siblings had inflammatory bowel disease. <b>Main outcome measures</b> Standardised incidence ratios and rate ratios as measures of relative risk. <b>Results</b> During 11.1 million years of follow-up in the appendicectomy cohort, 1192 patients developed ulcerative colitis (10.8 per 100 000 person years). Appendicectomy without underlying inflammation was not associated with reduced risk (standardised incidence ratio 1.04, 95% confidence interval 0.95 to 1.15). Before the age of 20, however, appendicectomy for appendicitis (0.45, 0.39 to 0.53) or mesenteric lymphadenitis (0.65, 0.46 to 0.90) was associated with significant risk reduction. A similar pattern was seen in those with affected relatives, whose overall risk of ulcerative colitis was clearly higher than the background risk (1404 observed <i>v</i> 446 expected; standardised incidence ratio 3.15, 2.99 to 3.32). In this cohort, appendicectomy without underlying appendicitis did not modify risk (rate ratio 1.04, 0.66 to 1.55, <i>v</i> no appendicectomy), while risk after appendicectomy for appendicitis was halved (0.49, 0.31 to 0.74). <b>Conclusions</b> In individuals with or without a familial predisposition to inflammatory bowel disease, appendicitis and mesenteric lymphadenitis during childhood or adolescence are linked to a significantly reduced risk of ulcerative colitis in adulthood. Appendicectomy itself does not protect against ulcerative colitis.
Some Mechanical Properties of Isolated Mammalian Cardiac Muscle
Authors: BRIAN F. HOFFMAN, ARTHUR L. BASSETT, HERBERT J. BARTELSTONE
Journal: Circulation Research (1968)

Isolated preparations of mammalian cardiac muscle have been employed to study possible mechanisms responsible for changes in diastolic compliance. Muscles have been studied at rest and during isometric and afterloaded contractions, at fixed initial length and during programmed, cyclic changes in length, and under the influence of paired stimulation, catecholamines, and elevated extracellular calcium concentrations. The results obtained indicate that, although there is a series viscous element in cardiac muscle, which accounts for stress-relaxation, some changes in compliance apparently result from alterations in the extensibility of the contractile element. This conclusion is based primarily on experiments showing shifts in the apex of the length-tension curve produced by action of inotropic agents which alter diastolic compliance and on experiments showing that the rate and extent of relaxation of afterloaded contractions depend on the extent of shortening during contraction.
IDIOTYPIC DETERMINANTS OF IMMUNOGLOBULIN M DETECTED ON THE SURFACE OF HUMAN LYMPHOCYTES BY CYTOTOXICITY ASSAYS
Authors: P. Wernet, T. Feizi, H. G. Kunkel
Journal: The Journal of Experimental Medicine (1972)

The complement-mediated cytotoxicity assay has been used to demonstrate surface immunoglobulin determinants on human peripheral blood lymphocytes. In two individuals with monoclonal serum IgM components, idiotypic antisera demonstrated similar components on a significant proportion of the peripheral blood lymphocytes.
Author's response: allergic rhinitis and asthma require an integrated management
Authors: Eric de Groot
Journal: Thorax (2012)

I thank Drs Camargos and colleagues for their comments1 regarding our paper.2 I agree with our Brazilian colleagues that additional randomised controlled trials are needed assessing the effect of allergic rhinitis treatment on asthma control in children.

In the study by Camargos et al , steroid naive asthmatic patients received fluticasone propionate either through a face …
Histochemical and immunohistochemical evidence for hepatic zone 3 distribution of alcohol dehydrogenase in rats
Authors: Shinzo Kato, Hiromasa Ishii, Sadakazu Aiso, Shuji Yamashita, Daisuke Ito, Masaharu Tsuchiya
Journal: Hepatology (1990)

The distribution of alcohol dehydrogenase in the hepatic acinus was examined by both histochemical and immunohistochemical approaches. The immunohistochemical method using anti-alcohol dehydrogenase antibody indicated zone 3 predominance of this enzyme in the hepatic acinus, whereas a conventional histochemical method showed slight zone 1 predominance. However, when the histochemical technique was improved by using 2% glutaraldehyde instead of formalin for fixation and by adding phenazine methosulfate (0.33 mmol/L) to the staining incubation mixture, this method also supported zone 3 predominance of alcohol dehydrogenase. Evidence for zone 3 distribution of alcohol dehydrogenase may be of value in elucidating the mechanism of zone 3 liver damage by alcohol. (Hepatology 1990;12:66-69).
Safety and side effects of sustained-release niacin
Authors: M. Shields
Journal: JAMA (1994)

To the Editor.  —The recent article by Dr McKenney and colleagues 1 is quite misleading with regard to its conclusions concerning IR niacin. The premise of the study was to distinguish between the effects of IR and SR niacin, which the authors did accomplish, but the two compounds were not distinguished adequately in the authors' conclusions.  In addition, the niacin was not given in the correct manner to eliminate flushing in this study. To minimize flushing and other side effects one starts with a small dose (50 mg three times daily) with food. After several days the flushing will cease. If the daily dose is gradually increased by small increments over several weeks, full therapeutic doses can eventually be tolerated with minimal to no vasodilatory or other uncomfortable effects. 2   McKenney et al verify once again that vasodilatory symptoms are the primary symptoms associated with IR niacin therapy. All of
PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?
Authors: GREGOR HASLER
Journal: World Psychiatry (2010)

Due to the clinical and etiological heterogeneity of major depressive disorder, it has been difficult to elucidate its pathophysiology. Current neurobiological theories with the most valid empirical foundation and the highest clinical relevance are reviewed with respect to their strengths and weaknesses. The selected theories are based on studies investigating psychosocial stress and stress hormones, neurotransmitters such as serotonin, norepinephrine, dopamine, glutamate and gamma-aminobutyric acid (GABA), neurocircuitry, neurotrophic factors, and circadian rhythms. Because all theories of depression apply to only some types of depressed patients but not others, and because depressive pathophysiology may vary considerably across the course of illness, the current extant knowledge argues against a unified hypothesis of depression. As a consequence, antidepressant treatments, including psychological and biological approaches, should be tailored for individual patients and disease states. Individual depression hypotheses based on neurobiological knowledge are discussed in terms of their interest to both clinicians in daily practice and clinical researchers developing novel therapies.
A Phase I Clinical Trial of Single-Dose Intrapleural IFN-β Gene Transfer for Malignant Pleural Mesothelioma and Metastatic Pleural Effusions: High Rate of Antitumor Immune Responses
Authors: Daniel H. Sterman, Adri Recio, Richard G. Carroll, Colin T. Gillespie, Andrew Haas, Anil Vachani, Veena Kapoor, Jing Sun, Richard Hodinka, Jennifer L. Brown, Michael J. Corbley, Michael Parr, Mitchell Ho, Ira Pastan, Michael Machuzak, William Benedict, Xin-qiao Zhang, Elaina M. Lord, Leslie A. Litzky, Daniel F. Heitjan, Carl H. June, Larry R. Kaiser, Robert H. Vonderheide, Steven M. Albelda
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This phase 1 dose escalation study evaluated the safety and feasibility of single-dose intrapleural IFN-β gene transfer using an adenoviral vector (Ad.IFN-β) in patients with malignant pleural mesothelioma (MPM) and metastatic pleural effusions (MPE). Experimental Design: Ad.IFN-β was administered through an indwelling pleural catheter in doses ranging from 9 × 1011 to 3 × 1012 viral particles (vp) in two cohorts of patients with MPM (7 patients) and MPE (3 patients). Subjects were evaluated for (a) toxicity, (b) gene transfer, (c) humoral, cellular, and cytokine-mediated immune responses, and (d) tumor responses via 18-fluorodeoxyglucose-positron emission tomography scans and chest computed tomography scans. Results: Intrapleural Ad.IFN-β was generally well tolerated with transient lymphopenia as the most common side effect. The maximally tolerated dose achieved was 9 × 1011 vp secondary to idiosyncratic dose-limiting toxicities (hypoxia and liver function abnormalities) in two patients treated at 3 × 1012 vp. The presence of the vector did not elicit a marked cellular infiltrate in the pleural space. Intrapleural levels of cytokines were highly variable at baseline and after response to gene transfer. Gene transfer was documented in 7 of the 10 patients by demonstration of IFN-β message or protein. Antitumor immune responses were elicited in 7 of the 10 patients and included the detection of cytotoxic T cells (1 patient), activation of circulating natural killer cells (2 patients), and humoral responses to known (Simian virus 40 large T antigen and mesothelin) and unknown tumor antigens (7 patients). Four of 10 patients showed meaningful clinical responses defined as disease stability and/or regression on 18-fluorodeoxyglucose-positron emission tomography and computed tomography scans at day 60 after vector infusion. Conclusions: Intrapleural instillation of Ad.IFN-β is a potentially useful approach for the generation of antitumor immune responses in MPM and MPE patients and should be investigated further for overall clinical efficacy.
Simultaneous recordings of oesophageal acid exposure with conventional pH monitoring and a wireless system (Bravo)
Authors: S B. des Varannes
Journal: Gut (2005)

<b>Objectives:</b> Oesophageal pH monitoring is a useful test for the diagnosis of gastro-oesophageal reflux disease (GORD) but has some limitations related to the nasopharyngeal electrode. Recently, a telemetric catheter free system (CFS) (Bravo; Medtronic) was developed. The aim of this study was to determine the concordance of data between the conventional pH measurement system (CPHMS) and the CFS Bravo. <b>Methods:</b> Forty patients with symptoms suggestive of GORD underwent 24 hour oesophageal pH monitoring using the CPHMS with a nasopharyngeal electrode and the Bravo CFS simultaneously. The sensitive tips of both electrodes were positioned at the same level under fluoroscopy. In addition to automatic analysis, each reflux episode was checked visually and characterised. <b>Results:</b> There was a significant correlation (<i>r</i> = 0.87, p&lt;0.0001) between the 24 hour oesophageal acid exposures recorded by the CPHMS and the CFS. Twenty four hour oesophageal acid exposure was significantly lower with the CFS than with the CPHMS (2.4 (0.4–8.7) <i>v</i> 3.6 (0.7–8.6); p&lt; 0.0001). Consequently, with the CFS, the cut off level for the diagnosis of GORD, as calculated from the regression equation, was 2.9% (for the 4.2% cut off determined in controls with the CPHMS). After this adjustment, concordance of the diagnosis of GORD was 88% (kappa 0.760). Diagnosis of GORD was established in more patients with the CFS 48 hour results than with the 24 hour results. <b>Conclusions:</b> Despite strong correlations between oesophageal acid exposure recorded with the two devices, the Bravo CFS significantly under recorded acid exposure compared with the CPHMS. Provided some correcting factors are used, the Bravo CFS can improve the sensitivity of pHmetry for the diagnosis of GORD by allowing more prolonged recordings.