tbuckley/cabot-search huggingface dataset:
Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer
Authors: Ronald C. Bruntz, Craig W. Lindsley, H. Alex Brown
Journal: Pharmacological Reviews (2014)

Phospholipase D is a ubiquitous class of enzymes that generates phosphatidic acid as an intracellular signaling species. The phospholipase D superfamily plays a central role in a variety of functions in prokaryotes, viruses, yeast, fungi, plants, and eukaryotic species. In mammalian cells, the pathways modulating catalytic activity involve a variety of cellular signaling components, including G protein–coupled receptors, receptor tyrosine kinases, polyphosphatidylinositol lipids, Ras/Rho/ADP-ribosylation factor GTPases, and conventional isoforms of protein kinase C, among others. Recent findings have shown that phosphatidic acid generated by phospholipase D plays roles in numerous essential cellular functions, such as vesicular trafficking, exocytosis, autophagy, regulation of cellular metabolism, and tumorigenesis. Many of these cellular events are modulated by the actions of phosphatidic acid, and identification of two targets (mammalian target of rapamycin and Akt kinase) has especially highlighted a role for phospholipase D in the regulation of cellular metabolism. Phospholipase D is a regulator of intercellular signaling and metabolic pathways, particularly in cells that are under stress conditions. This review provides a comprehensive overview of the regulation of phospholipase D activity and its modulation of cellular signaling pathways and functions.
Dose-Dependent Effect of Endothelin-1 on Blood Flow to Normal and Collateral-Dependent Myocardium
Authors: Jay H. Traverse, Dianne Judd, Robert J. Bache
Journal: Circulation (1996)

Background Plasma levels of endothelin-1 (ET-1) increase during ischemia and could potentially contribute to impairment of myocardial blood flow (MBF). Because collateral vessels demonstrate enhanced responsiveness to certain vasoconstrictors, blood flow to collateral-dependent myocardium could be particularly sensitive to increases in ET-1 levels. Methods and Results Studies were performed in 13 dogs in which collateral vessel development was produced by fluoroscopic embolization of the midleft anterior descending coronary artery with a hollow plug 4 to 6 weeks before the study. MBF was measured with radioactive microspheres at baseline and during 30-minute infusions of ET-1 (1, 10, and 100 ng/min) into the left main coronary artery. Because ET-1 stimulates endothelial prostacyclin release, aortic and coronary sinus levels of ET-1 and 6-keto–prostaglandin F 1α were measured at the end of each infusion. ET-1 increased MBF from 0.82 mL·min −1 ·g −1 at baseline to 0.92 mL·min −1 ·g −1 at 10 ng/min ( P &lt;.05), which corresponded to a coronary plasma concentration of 73±16 pg/mL. Blood flow in the collateral zone was less (0.74 mL·min −1 ·g −1 ) than in the normal zone ( P &lt;.05) and did not increase at an ET-1 dose of 10 ng/min. MBF in the normal and collateral zones significantly decreased when ET-1 was increased to 100 ng/min, corresponding to a coronary sinus concentration of 175±45 pg/mL ( P &lt;.05). ET-1 produced dose-related increases in aortic and coronary sinus 6-keto–prostaglandin F 1α and the transcoronary difference ( P &lt;.05). To assess the importance of prostacyclin in opposing the vasoconstriction produced by ET-1, additional studies were performed after cyclooxygenase blockade with indomethacin. After indomethacin administration, ET-1 (10 ng/min) caused a 120±23% increase in collateral vascular resistance ( P &lt;.05) and abolished the vasodilation that this dose produced in the normal zone. Conclusions Blood flow to normal myocardium is increased at moderate plasma elevations of ET-1, whereas collateral blood flow is unchanged. Only at significantly elevated plasma concentrations of ET-1 is blood flow to normal and collateral-dependent myocardium impaired. Coronary endothelial production of prostacyclin in response to increasing concentrations of ET-1 represents an important means of blunting the vasoconstrictor properties of ET-1 in the canine coronary circulation. Coronary collateral vessels demonstrate a much greater dependence on prostacyclin production in blunting the vasoconstrictor properties of ET-1.
Immunohistochemical analysis of measles related antigen in IBD Reply
Authors: A J WAKEFIELD
Journal: Gut (2001)

Editor,—What is one to make of the immunohistochemical study of Iizuka et al ( Gut 2000; 46: 163–169 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4])? Before addressing the possible scientific implications of their findings, it is worth clarifying a few points with respect to our own research. Iizuka et al state that “the measles hypothesis is based on the theory that measles antibody recognises measles virus itself and the measles virus antigen is uniquely present in Crohn's disease.” Is this the authors' hypothesis? It is certainly not ours. That the measles antibody used in our studies (not that used by the authors in the present study) recognises the measles virus is not in doubt. The appropriate question is “does the antibody detect human antigenic epitopes in addition to measles virus N-protein?” Specificity studies in our own laboratory, including application to mixed preparations of measles virus infected and uninfected cells, application to cell lines infected with other viruses, and tissue studies incorporating in situ hybridisation (ISH) and combined ISH-reverse transcription-polymerase chain reaction (RT-PCR)-ISH for measles virus N-gene in serial tissue sections of infected human tissues suggest that the antibody, when used appropriately, is specific for measles virus. Our own hypothesis relates not to the unique presence of measles in Crohn's disease but rather to the specific localisation of the virus to the hallmark lesions of this disease—granulomas and secondary lymphoid reactions—that are themselves a likely response to persistent and potentially causative antigen(s). While the focus of our studies has been the exclusive presence of viral antigen in these foci in Crohn's disease, Iizuka et al have assiduously avoided these pathological structures altogether. Instead, they have identified a pattern of non-specific … M Iizuka, First Department of Internal Medicine, Akita University School of Medicine, 1–1–1 Hondo, Akita 010–8543, Japan.iizuka{at}med.akita-u.ac.jp [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2Bmedical%2Bvirology%26rft.stitle%253DJ%2BMed%2BVirol%26rft.aulast%253DWakefield%26rft.auinit1%253DA.%2BJ.%26rft.volume%253D39%26rft.issue%253D4%26rft.spage%253D345%26rft.epage%253D353%26rft.atitle%253DEvidence%2Bof%2Bpersistent%2Bmeasles%2Bvirus%2Binfection%2Bin%2BCrohn%2527s%2Bdisease.%26rft_id%253Dinfo%253Adoi%252F10.1002%252Fjmv.1890390415%26rft_id%253Dinfo%253Apmid%252F8492105%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1002/jmv.1890390415&link_type=DOI [3]: /lookup/external-ref?access_num=8492105&link_type=MED&atom=%2Fgutjnl%2F48%2F1%2F136.atom [4]: /lookup/external-ref?access_num=A1993KX33200014&link_type=ISI
Effects of low flow on pulmonary vascular flow–pressure curves and pulmonary vascular impedance
Authors: S Brimioulle
Journal: Cardiovascular Research (1999)

Objective: Flow–pressure curves and vascular impedance are commonly used to investigate pulmonary circulation, but they may be affected at low flow by reflex neurohumoral activation. We therefore investigated the mechanical effects and the reflex effects of decreased flow on pulmonary vascular resistance and impedance. Methods: In ten anaesthetized dogs, we compared flow–pressure curves generated in less than 10 s to prevent sympathetic activation (fast curves), or generated over 20–30 min to allow neurohumoral equilibration (slow curves), in hyperoxia (inspired oxygen, 40%) and in hypoxia (inspired oxygen, 10%), before and after adrenergic blockade by phentolamine and propranolol. Resistance was assessed from the flow–pressure relationship. Impedance was computed from instantaneous flow and pressure obtained with an ultrasonic flowmeter and a micromanometer-tipped catheter. Results: At baseline, fast flow–pressure curves were steeper and had a lower pressure intercept. Transient low flow did not affect heart rate or pulmonary arterial elastance. Sustained low flow increased heart rate, resistance and elastance, suggesting baroreceptor-induced sympathetic stimulation. After adrenergic blockade, no difference persisted between effects of transient and sustained low flow. In hypoxia, slow and fast flow–pressure curves were similar. Hypoxia increased heart rate and resistance but did not decrease elastance, suggesting chemoreceptor-induced sympathetic stimulation. In hypoxia, differences between transient and sustained low flow were no longer significant, and were completely suppressed by adrenergic blockade. In two additional dogs, epinephrine infusion increased pulmonary vascular resistance and elastance. Conclusions: We conclude that (1) compared to transient low flow, sustained low flow is associated with increases in distal resistance and proximal elastance due to sympathetic stimulation and (2) these differences between the effects of transient and sustained low flow do not persist in hypoxia, because of an already present chemoreceptor-induced sympathetic stimulation.
Mitral valve area in combined mitral stenosis and regurgitation.
Authors: J Askenazi, C J Carlson, J S Alpert, L Dexter
Journal: Circulation (1976)

Eight patients with mixed mitral stenosis and regurgitation underwent hemodynamic and angiographic study prior to mitral valve replacement. The stenotic orifice of the mitral valve was calculated employing the total left ventricular stroke volume by cineangiography as the numerator of the Gorlin Formula. Excellent agreement with the measured orifice of the mitral valve was obtained using a value of 37.9 (0.85 X 44.5) for the constant in the Gorlin formula as recommended by Cohen and Gorlin. Recalculation of this constant independently by our data yielded a value that was almost identical. Regurgitant flows and orifice sizes were calculated for each patient using the same constant as for calculation of the stenotic orifices.
Inducible nitric oxide synthase protein expression after in vivo endothelial denudation of the rat carotid artery: role of the platelets
Authors: J.A. Rodriguez-Feo, F. González-Fernández, S. Casado, J.M. Rubio, I. Millás, M. Garcia-Durán, L. Rico, J. Farré, L. Sánchez de Miguel, A. López-Farré
Journal: Journal of the American College of Cardiology (1998)
Viral and host factors in early hepatitis C virus infection
Authors: James W. Mosley, Eva A. Operskalski, Leslie H. Tobler, William W. Andrews, Bruce Phelps, Janel Dockter, Cristina Giachetti, Michael P. Busch
Journal: Hepatology (2005)

Since 1980, the Transfusion-transmitted Viruses Study (TTVS) (1974-1980) has continued to maintain its computerized database and stored sera to enable ongoing study of new transfusion events since the 1970s. Most recently, we have used this resource to study parameters of acute hepatitis C virus (HCV) infection among 94 donor-recipient pairs in which there was transmission. In addition, frequent recipient observations permitted further characterization of the early phase of the infection's course. Donor RNA load ranged from 3.7 to 3,160,000 IU/mL. Onset of recipient viremia was judged from a total of 67 sera collected during the 4th through 8th days posttransfusion; only 2 of the 67 sera were still RNA nonreactive by that time. The recipients' latent periods to an alanine aminotransferase (ALT) elevation of > or =90 IU/L ranged from 6 to 112 days (median, 46 days) and was shorter with higher donor RNA levels. Descriptors of the recipient's illness showed several strongly positive and negative correlations. The latent period tended to be shorter in the 37% of cases that were clinically overt. Attributes of donors with genotypes 1 and non-1 and subtypes 1a and 1b did not differ significantly. Recipients with genotype 1 strains had shorter latent intervals than non-1 strains. On multivariate analysis, latent period was significantly associated (negatively) only with the highest ALT level during the first 120 days of follow-up (P = .014). In conclusion, host factors are more important determinants of acute HCV infection dynamics than virus-associated factors.
Prostacyclin for Secondary Pulmonary Hypertension
Authors: Vallerie V. McLaughlin, Stuart Rich
Journal: Annals of Internal Medicine (2000)

Letters18 January 2000Prostacyclin for Secondary Pulmonary HypertensionVallerie V. McLaughlin, MD and Stuart Rich, MDVallerie V. McLaughlin, MDRush Heart Institute; Chicago, IL 60612 (McLaughlin)Rush Heart Institute; Chicago, IL 60612 (Rich)Search for more papers by this author and Stuart Rich, MDRush Heart Institute; Chicago, IL 60612 (McLaughlin)Rush Heart Institute; Chicago, IL 60612 (Rich)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-2-200001180-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Mild pulmonary hypertension is not uncommon in the setting of sickle cell disease and may be present in up to two thirds of patients, along with left atrial and left ventricular dilatation. In fact, pulmonary hypertension may be related to elevated left-sided filling pressures or a high output state from anemia. Although Kaur and colleagues did not give the individual data for the four patients with sickle cell disease, such as the mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output, we are given the pulmonary resistance. Of note, the pulmonary vascular resistance in these four ... Author, Article, and Disclosure InformationAffiliations: Rush Heart Institute; Chicago, IL 60612 (McLaughlin)Rush Heart Institute; Chicago, IL 60612 (Rich) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCompassionate Use of Continuous Prostacyclin in the Management of Secondary Pulmonary Hypertension: A Case Series Vallerie V. McLaughlin , Diane E. Genthner , Maureen M. Panella , Dina M. Hess , and Stuart Rich Prostacyclin for Secondary Pulmonary Hypertension Karamjit Kaur , Bernice Brown , and Fred Lombardo Metrics 18 January 2000Volume 132, Issue 2Page: 165KeywordsCardiac outputCase seriesProstacyclinPulmonary arteriesPulmonary capillary wedgePulmonary diseasesPulmonary hypertensionPulmonary vascular diseasesPulmonary vascular resistanceSickle cell disease Issue Published: 18 January 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Letter by Eller et al Regarding Article, “Lower Mortality from Coronary Heart Disease and Stroke at Higher Altitudes in Switzerland”
Authors: Kathrin Eller, Ivan Tancevski, Philipp Eller
Journal: Circulation (2010)

We read with great interest the article titled "Lower Mortality from Coronary Heart Disease and Stroke at Higher Altitudes in Switzerland" by Faeh et al. 1 In the large Swiss National Cohort, the authors convincingly show a lower mortality from coronary heart disease (Ϫ22% per 1000 m) and stroke (Ϫ12% per 1000 m) with increasing altitude.They conclude that this effect may be due to factors related to climate, although there was no adjustment for classic risk factors of atherosclerosis such as diabetes mellitus.Interestingly, there is a clear regional variability in the incidence of diabetes mellitus type 2 and its sequel, end-stage renal failure, in the neighboring Alpine state of Austria, where mountainous areas such as Tyrol have a significantly lower incidence of type 2 diabetes mellitus in comparison with lowlands. 2Like German Switzerland, Austria has an ethnically homogenous population, universal access to health care, and places of residence allocated between 200 and 2000 m with only minimal changes in geographic latitude.Clinician investigators and article reviewers would greatly benefit from knowing whether there is a similar regional variability in the incidence of type 2 diabetes mellitus in Switzerland, inasmuch as diabetes mellitus constitutes a crucial risk factor for atherosclerosis, 3 and may explain on its own the different mortality for coronary heart disease and stroke in highlanders and lowlanders in Switzerland.
Biomarkers of HPV in Head and Neck Squamous Cell Carcinoma
Authors: Caihua Liang, Carmen J. Marsit, Michael D. McClean, Heather H. Nelson, Brock C. Christensen, Robert I. Haddad, John R. Clark, Richard O. Wein, Gregory A. Grillone, E. Andres Houseman, Gordana Halec, Tim Waterboer, Michael Pawlita, Jeffrey F. Krane, Karl T. Kelsey
Journal: Cancer Research (2012)

Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.
Infants of low birth weight.
Authors: H B Valman
Journal: BMJ (1979)

S2Low birth weight infants weigh 2500 g or less at birth.Infants may be 32 1 /// /// _ IS -small at birth owing to a short gestation period (born too early) or because 3,11 13 /// /// / of a retarded growth rate.Whenthe period of gestation is less than 37 36-<1 fhD /// /completed weeks the infant is called preterm.A baby with retarded growth 24-10, /// ///5 2rate is "light-for-dates" and may be either malnourished or rarely hypoplastic (for example, an infant with a chromosome abnormality).Some babies who are preterm are also light-for-dates.
Femoral Neuropathy in Scurvy
Authors: James Hood
Journal: New England Journal of Medicine (1969)

FEMORAL neuropathy may occur in various hemorrhagic disorders, but has not been recorded in scurvy. This is a report of the occurrence of bilateral femoral neuropathy in scurvy.Case ReportIn a study of the metabolism of L-ascorbic acid in experimentally induced scurvy, a healthy 26-year-old man (plasma ascorbic acid of 1.08 mg per 100 ml), who had given his informed consent, received no ascorbic acid for 91 days. On the 71st day he complained of numbness of the calves; hypesthesia to light touch and pinprick was present on the medial aspect of each calf (when the plasma ascorbic acid . . .
High sensitivity cardiac troponin in patients with chest pain
Authors: A. S. V. Shah, D. E. Newby, N. L. Mills
Journal: BMJ (2013)

For most patients presenting with a spinal cord syndrome MR scanning has become the key investigation in establishing the diagnosis. However, myelopathy with normal spinal imaging remains a common clinical conundrum. In this review we discuss the diagnoses to consider for the neurologist presented with a patient with “MR normal myelopathy”. We will illustrate this scenario with a series of short cases and consider the further investigation of “MRI normal” myelopathy.
Mutations in the Cone-Rod Homeobox Gene Are Associated with the Cone-Rod Dystrophy Photoreceptor Degeneration
Authors: Prabodha K Swain, Shiming Chen, Qing-Liang Wang, Louisa M Affatigato, Caraline L Coats, Kevin D Brady, Gerald A Fishman, Samuel G Jacobson, Anand Swaroop, Edwin Stone, Paul A Sieving, Donald J Zack
Journal: Neuron (1997)

Crx is a novel paired-like homeodomain protein that is expressed predominantly in retinal photoreceptors and pinealocytes. Its gene has been mapped to chromosome 19q13.3, the site of a disease locus for autosomal dominant cone-rod dystrophy (CORDII). Analysis of the proband from a family with autosomal dominant CORD revealed an Arg41Trp substitution in the third residue of the CRX homeodomain. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. Recombinant CRX homeodomain containing the Arg41Trp substitution showed decreased DNA binding activity. Analysis of another 169 CORD probands identified three additional CRX sequence variations (Arg41Gln, Val242Met, and a 4 bp deletion in codons 196/7) that were not found among the controls. This data suggests that mutations in the CRX gene are associated with photoreceptor degeneration and that the Crx protein is necessary for the maintenance of normal cone and rod function.
Cyril Joseph Thornberry
Authors: David Thornberry
Journal: BMJ (2004)

Former consultant obstetrician and gynaecologist Birkenhead and Wallasey Hospitals (b Northern Ireland 1918; q Royal College of Surgeons of Ireland 1941; FRCOG), died from complications of leukaemia on 13 June 2004.​2004.




Figure 1




Joe did house jobs in Huddersfield before serving as a surgeon lieutenant in the Royal Navy in the Mediterranean and the Far East. On his demobilisation he worked in orthopaedics in Plymouth before embarking on a career in obstetrics and gynaecology. He was appointed consultant in Birkenhead in 1962. Joe was an enthusiastic dinghy sailor and used to act as medical officer at the Oulton Park Motor Racing Circuit and occasionally for Tranmere Rovers Football Club, and later at Newton Abbot Race Course. He leaves a wife, Elizabeth, and two children.
BMA meeting: Market reforms have failed to deliver better health care, say doctors
Authors: A. Cole
Journal: BMJ (2008)

Doctors at the BMA’s annual conference in Edinburgh have united in calling for an end to England’s market driven reforms in health care, which, they claimed, threaten to undermine and fragment core NHS services.

Members of the representative body voted by large majorities to press to keep NHS services within the public sector and to inform the public of the detrimental effects of handing over health services to the private sector. They also proposed that NHS providers should have “preferred provider” status in delivering NHS care to NHS patients.

The private sector should be used to treat NHS patients only when the NHS had insufficient capacity, said Stephen Austin from …