tbuckley/cabot-search huggingface dataset:
Effects of purified perforin and granzyme A from cytotoxic T lymphocytes on guinea pig ventricular myocytes
Authors: B. Felzen, G. Berke, D. Rosen, R. Coleman, J. Tschopp, J. D.-E Young, O. Binah
Journal: Cardiovascular Research (1994)

Objective: Involvement of cytotoxic T lymphocytes (CTL) in heart transplant rejection as well as in viral myocarditis is well established, but the precise mechanisms whereby infiltrating CTL damage the myocardium are unknown. The aim of the study was to investigate how CTL derived perforin, the serine protease granzyme A, and the combination of both, damage guinea pig ventricular myocytes. Methods: Action potentials and membrane currents were recorded by means of the whole cell configuration from guinea pig ventricular myocytes. Results: Resembling the effects of CTL derived lytic granules, perforin caused gradual myocyte shortening and contracture, leading to complete loss of the rod shaped morphology and to cell destruction. These changes were preceded by shortening of action potential duration and reduction of resting potential and action potential amplitude, followed by complete inexcitability. Granzyme A alone was ineffective, but accelerated the deleterious effects of perforin on the morphological and electrophysiological properties of myocytes. The effects of perforin were further evaluated by measuring membrane currents by means of the whole cell voltage clamp. Perforin induced discrete changes in membrane current, reminiscent of single ion channels, with large conductance and open time of up to several seconds. Linear regression analysis of the channel I-V relations resulted in a conductance of 890 pS and a reversal potential of −7.6 mV. These results suggest that perforin induces large non-selective channels, which can account for most of the observed adverse effects. Conclusions: As CTL participate in the immunological rejection of the transplanted heart, it is conceivable, but remains to be shown, that part of this damage is inflicted by perforin containing lytic granules. Cardiovascular Research 1994;28:643-649
TCT-322 Utility of the Residual SYNTAX Score In Patients With Diabetes Mellitus After Percutaneous Coronary Intervention
Authors: Elias Sanidas, Philippe Genereux, Tullio Palmerini, Adriano Caixeta, Rakesh Malhotra, Ajay J. Kirtane, Ke Xu, Gary S. Mintz, Sorin Brener, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2013)
Clinical and Biological Aspects of Bereavement and Loss-Induced Depression: A Reappraisal
Authors: M. Biondi, A. Picardi
Journal: Psychotherapy and Psychosomatics (1996)

Loss and bereavement can be regarded as risk factors for the development of psychiatric and medical illness. Vulnerability to physical illness and mortality are increased during the first 2 years of bereavement, with men at higher risk than women. Symptoms of anxiety and a frank depressive syndrome are common during the first months of bereavement and, although depressive symptoms are usually transient and self-limited, bereaved individuals not rarely go on to develop major depression. In our perspective, loss perceived as irreparable, and persistence of perceived loss may favour the development of complicated grief and depression. Factors such as unexpectedness, absence of social support, concurrent loss or illness, and grief proneness may predict poor adjustment after bereavement. Complicated bereavement should be distinguished from uncomplicated bereavement, because patients with the latter need no treatment. In humans, there is evidence of increased adrenocortical activity and altered immune function following bereavement, whereas in non-human primates, biogenic amine systems appear to be involved in the response to maternal or social separation. According to a 'psychosomatic view of the brain', critical life events can both affect brain neurotransmitters and contribute to psychological and somatic symptoms of depression. Emotional events may be transduced into long-lasting brain changes, involving neurotransmitters, neuropeptides and receptors. Although only very limited evidence exists, long-term consequences could involve changes at the gene expression level.
Differential association of polymorphisms in the TNFalpha region with psoriatic arthritis but not psoriasis
Authors: T Höhler, S Grossmann, B Stradmann-Bellinghausen, W Kaluza, E Reuss, K de Vlam, E Veys, E Märker-Hermann
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To investigate the potential association of tumour necrosis factor α (TNFα) microsatellite and promoter alleles with psoriatic arthritis (PsA). Methods: DNA from 89 white patients with PsA, 65 patients with psoriasis, and 99 healthy white controls was investigated for two TNFα promoter (–238 and –308) and three microsatellite polymorphisms (TNFa, c, and d). Patients had previously been studied by serology for HLA class I antigens and by sequence-specific polymerase chain reaction for DRB1* alleles. In addition, TNFα production of Ficoll separated peripheral blood mononuclear cells (PBMC) into culture supernatants after stimulation with lipopolysaccharide, αCD3 antibodies, phytohaemagglutinin, and streptococcal superantigen C was determined. Results: A significant, HLA class I independent increase of the TNFa6c1d3 haplotype was found in the group with PsA but not among patients with psoriasis (32% <i>v</i> 8%, pc&lt;0.008; relative risk (RR)=5.3). In addition, patients with PsA showed a marked decrease of the TNF308A promoter allele (6% <i>v</i> 18%; pc&lt;0.008; RR=3.5) compared with healthy controls, which was independent of the increased frequency of the –238A polymorphism in this group. PBMC from patients with PsA secreted significantly less TNFα than cells from patients without arthritis. In particular, the TNFa6 microsatellite was associated with decreased TNFα production. Conclusion: These data indicate that allelic variations at the TNFα locus influence susceptibility to PsA. Decreased production of TNFα is at least in part genetically determined and might be related to the development of arthritis. However, the association of the TNF308G allele with the disease also points to other disease related haplotypes with still unknown susceptibility genes.
Studies on the effects of topical retinoic acid on photoageing
Authors: R. MARKS, L. LEVER
Journal: British Journal of Dermatology (1990)

Journal Article Studies on the effects of topical retinoic acid on photoageing R. MARKS, R. MARKS Department of Medicine (Dermatology), University of Wales College of Medicine, Cardiff, U.K. Professor R. Marks, Department of Medicine (Dermatology), University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, U.K. Search for other works by this author on: Oxford Academic Google Scholar L. LEVER L. LEVER Department of Medicine (Dermatology), University of Wales College of Medicine, Cardiff, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue s35, 1 April 1990, Pages 93–95, https://doi.org/10.1111/j.1365-2133.1990.tb16132.x Published: 01 April 1990
Antibodies Against the Hepatic Asialoglycoprotein Receptor Perfused In Situ Preferentially Attach to Periportal Liver Cells in the Rat
Authors: Barbara M. McFarlane, Jozsef Sipos, Christopher D. Gove, Ian G. McFarlane, Roger Williams
Journal: Hepatology (1990)

Autoantibodies reacting with the galactose–specific hepatic asialoglycoprotein receptor—a liver–specific component expressed on the surfaces of hepatocytes—are often found in patients with chronic active hepatitis of presumed autoimmune origin. As part of an investigation into whether these anti–asialoglycoprotein receptor antibodies might be involved in the development of periportal liver damage in chronic active hepatitis, livers of ether–anesthetized rats were perfused in situ with polyclonal guinea pig anti–rabbit asialoglycoprotein receptor or murine monoclonal antihuman galactose–specific hepatic asialoglycoprotein receptor antibodies in excess at &lt;8° C or, as a control, with guinea pig anti–human plasma protein antibodies or normal guinea pig serum. Rapid (1 min) antegrade (by way of portal vein) or retrograde (through hepatic veins by way of vena cava) perfusions were performed in a nonrecirculating (once–through) mode in Ca ++ –free medium. Blocks of liver tissue were immediately snapfrozen and the distribution of the antibody examined in cryostat sections by using an avidin–biotin immunohistochemical technique. In all of the perfusions with anti–asialoglycoprotein receptor (six antegrade, seven retrograde), the antibodies were found to be prominently and almost exclusively deposited on liver cells in the periportal areas. No deposition of immunoglobulins was detected in livers perfused with the control guinea pig sera. The findings suggest that the asialoglycoprotein receptor is expressed at high density mainly on cells in zone 1 of the hepatic lobule, and this may have implications for the development of periportal liver damage in chronic active hepatitis.(Hepatology 1990;11:408-415.)
THE SURGICAL TREATMENT OF UTERINE FIBRO-MYOMATA.
Authors: E. C. DUDLEY
Journal: JAMA (1896)

The object of this paper is not to enlarge upon a great variety of procedures which have become or seem destined to become obsolete, but rather to present briefly the more useful operations for the treatment of fibro-myomata of the uterus. The subject will be divided as follows: 1, palliative operations. 2, radical vaginal operations. 3, radical abdominal operations. <h3>I. PALLIATIVE OPERATIONS.</h3> The palliative operations are,<i>a</i>, curettage,<i>b</i>, electrolysis,<i>c</i>, ligature of the uterine arteries and broad ligaments,<i>d</i>, removal of the uterine appendages. <h3>a. Curettage.</h3> —The irritating presence of the tumor often gives rise to hemorrhagic endometritis. Curettage is therefore indicated precisely as it would be in hemorrhagic endometritis from any other cause. The operation is generally followed by a degree of relief from the menorrhagia, is seldom permanent in its results and must usually therefore be repeated again and again. It is especially useful in connection with
Antidepressants increase, rather than decrease, risk of suicidal behaviours in younger patients
Authors: T. J. Moore
Journal: BMJ (2014)

Lu and colleagues’ study contains four substantial flaws, any of which would be fatal to the authors’ premise that Food and Drug Administration warnings about suicide risks of antidepressants led to an increase in suicidal behaviours.1

Firstly, the authors acknowledge that the insurance claims data on which they rely is generally not suitable for detecting …
Nora Kathleen Woll
Authors: Penella J Woll
Journal: BMJ (2004)

Former general practitioner Bottesford, Leicestershire (b Tynemouth 1914; q Durham 1938; MBE), died from old age on 15 May 2004.​2004.




Figure 1




Kathleen was working as a house officer when the second world war broke out. As the Royal Army Medical Corps was not taking on women doctors, she enlisted in the Indian Medical Service, where she became a major. After the war she did postgraduate training in child health, working in London and Newcastle upon Tyne. She then became a singlehanded family practitioner for over 30 years. She continued her interest in child health by introducing antenatal and immunisation clinics. In 1956 she was found to have a meningioma. She underwent pioneering surgery, leaving her with a dense right hemiplegia and facial palsy. She taught herself to write and give injections with her left hand, and resumed her work.
Corticotropin-releasing hormone is produced by rat corticotropes and modulates ACTH secretion in a paracrine/autocrine fashion.
Authors: F P Giraldi, F Cavagnini
Journal: Journal of Clinical Investigation (1998)

Anterior pituitary hormone secretion is mainly regulated by hypothalamic releasing factors, which reach the pituitary via portal vessels. It has been demonstrated recently that these peptides can also be produced by the pituitary itself, thus possibly modulating hormone secretion in a paracrine/autocrine fashion. The object of this study was to seek evidence for the synthesis and secretion of corticotropin-releasing hormone (CRH) within the anterior pituitary and to ascertain its biological relevance. Messenger RNA from adult rat anterior pituitary fragments and cell cultures was reverse transcribed and subjected to PCR amplification using primers specific to the rat CRH gene. As in the hypothalamus, a single 232-bp band was obtained. The correspondence of the amplified fragment to the sequence of the CRH gene was confirmed by Southern blotting and restriction enzyme digestion. Combined in situ reverse transcription-PCR amplification/immunocytochemistry demonstrated the presence of CRH mRNA in corticotropes. Medium from anterior pituitary primary cultures contained approximately 7 pg/microg protein of CRH immunoreactivity which presented the same chromatographic profile on HPLC as the mature CRH peptide. Incubation of anterior pituitary cells with an antibody directed against CRH markedly reduced basal ACTH secretion compared with serum-treated control wells (0.89+/-0.11 vs. 1.74+/-0.14 ng/200,000 cells in control wells after 1 h, P < 0.05; 1.17+/-0.10 vs. 2.16+/-0. 39 ng/200,000 cells after 2 h, P < 0.05; 1.45+/-0.12 vs. 3.12+/-0.61 ng/200,000 cells after 3 h, P < 0.05). Further, the ACTH response to potassium and to forskolin was markedly blunted by the CRH antiserum as well as by the CRH antagonist, alpha-helical CRH(9-41). In conclusion, this study demonstrates the presence of CRH mRNA in normal rat corticotropes and the secretion of the mature peptide by the anterior pituitary, pointing to the production of CRH at the site of its target cells. In addition, intrapituitary CRH contributes in a paracrine/autocrine fashion to ACTH secretion.
Intermittent Claudication — Be Conservative
Authors: Jay D. Coffman
Journal: New England Journal of Medicine (1991)

Severe peripheral vascular disease is a common disorder that frequently creates substantial morbidity in our aging population. A nonsurgical approach to the treatment of intermittent claudication, one of the chief manifestations of the disease, was widely expected after the introduction of percutaneous transluminal angioplasty about 20 years ago. The article by Tunis and associates in this issue of the Journal 1 explores the effect of angioplasty on the rate of surgical procedures for peripheral vascular disease. The study raises many important issues, among them the epidemiologic features of the disease, the therapeutic approaches available for those affected, and the appropriateness of . . .
Concentrations of an activator protein for sphingolipid hydrolysis in liver and brain samples from patients with lysosomal storage diseases.
Authors: K Inui, D A Wenger
Journal: Journal of Clinical Investigation (1983)

The hydrolysis of sphingolipids by lysosomal enzymes requires the presence of additional proteins, which have been called activator proteins. The number of activator proteins, their specificity, exact mechanism of action, and response to a storage process all remain to be determined. In this study, antibodies to an activator protein known to bind sphingolipids and activate the enzymatic hydrolysis of GM1 ganglioside and sulfatide were used to estimate the concentration of this activator protein in small samples of liver and brain from patients with lysosomal storage diseases. By using rocket immunoelectrophoresis, the concentration of cross-reacting material (CRM) was determined. Control livers had an average of 0.95 +/- 0.18 (mean +/- 1 SD) microgram CRM/mg protein in the extracts, and control brains had an average of 0.25 +/- 0.14 microgram CRM/mg protein. Extremely high levels of CRM were found in extracts of livers from patients with type 1 GM1 gangliosidosis (15.1 and 16.9), and type A Niemann-Pick disease (10.7). Extracts of brain samples revealed a large amount of CRM in type 1 GM1 gangliosidosis (14.8), Tay-Sachs disease (5.3 and 8.7), and Sandhoff disease (13.5). Significantly elevated CRM was also measured in brain samples from patients with type 2 GM1 gangliosidosis, type A Niemann-Pick disease, metachromatic leukodystrophy, and Krabbe disease. The highest levels are found in those genetic diseases where the lipids stored, primarily or secondarily to the genetic defect, bind to this activator protein. This activator protein may have an important function in regulating intralysosomal lipid catabolism, and changes in its concentration in certain genetic diseases may be the cause of clinical, biochemical, and pathological heterogeneity found in the patients.
Government moves to end stigma of mental illness
Authors: Mark Gould
Journal: BMJ (2004)

The government's Social Exclusion Unit (SEU) has announced far-reaching proposals which it hopes will end the stigma and discrimination attached to mental illness and encourage people back into meaningful lives.This week the unit launched its report, Mental Health and Social Exclusion, which calls for health services to focus on the social as well as medical needs of hundreds of thousands of people excluded from wider society by mental illness.The report sets out a five year plan with an ambitious antistigma and discrimination campaign aimed at employers, schools, and the media, which it hopes will dispel cultural myths that people with mental illness are dangerous, unstable, and unemployable.All psychiatric patients in hospital are to be given vocational advice and support, and trusts will be told to strengthen links with job centres.NHS day centres must be redesigned with a focus on re-integrating patients into the community via job training, advice about employment, education, or voluntary work.
No-Smoking Policies in Hospitals
Authors: Edward A. Sceppa
Journal: JAMA (1992)

<h3>To the Editor.</h3> —I found the article by Joseph and O'Neil<sup>1</sup>to be an excellent account of how well hospital smoke-free policies may be implemented. However, I found the ethical implications of the article to be disturbing. Because hospitals' no-smoking policies are medically appropriate does not imply that they are ethically justifiable. The Department of Veterans Affairs (VA) certainly may prevent smoking patients from subjecting nonsmoking patients to the risks as well as the nuisance of passive smoke. However, it is much more difficult to justify preventing patients from smoking to promote their own health. Health promotion to attain the goal of personal longevity is, as I believe some authors have correctly argued,<sup>2,3</sup>the popular, personal ethic of today that is largely replacing older ethics, such as living life for the betterment of society or the attainment of an afterlife. To act contrary to the ethic of life
Diagnosis of Pulmonary Embolism
Authors: James F. Morris, Gerbail T. Krishnamurthy
Journal: Annals of Internal Medicine (1991)

Letters15 April 1991Diagnosis of Pulmonary EmbolismJames F. Morris, MD, Gerbail T. Krishnamurthy, MDJames F. Morris, MDSearch for more papers by this author, Gerbail T. Krishnamurthy, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-8-702 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editors: Hull and Raskob (1) urge a change in the way lung scans are interpreted (1). In their study, 23% (Biello criteria) or 25.5% (McNeil criteria) of patients with low-probability scans had angiographic evidence of pulmonary emboli. Of equal interest, 40.4% (Biello) or 38% (McNeil) of their patients with high-probability scans had no other evidence of pulmonary embolism. They urge a change in reporting low-probability ventilation-perfusion scans, but they offer no recommendations of their own.Most agree that normal pulmonary angiograms and lung scans rule out significant pulmonary embolism, but as Kipper and colleagues (2) point out, neither...References1. HullRaskob RG. Low-probability lung scan findings: a need for change. Ann Intern Med. 1991;114:142-3. LinkGoogle Scholar2. KipperMoserKortmanAshburn MKKW. Long term follow-up of patients with suspected pulmonary embolism and a normal lung scan. Chest. 1982;82:411-5. CrossrefMedlineGoogle Scholar3. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA. 1990;263:2753-9. CrossrefMedlineGoogle Scholar4. LeeBielloKumarSiegel MDBB. "Low-probability" ventilation-perfusion scintigrams: clinical outcomes in 99 patients. Radiology. 1985;156:497-500. CrossrefMedlineGoogle Scholar5. KrishnamurthyMorrisBobba GJV. Pulmonary embolism and deep venous thrombosis. Ann Intern Med. 1983;99:412-3. LinkGoogle Scholar1. HullRaskob RG. Low-probability lung scan findings: a need for change. Ann Intern Med. 1991;114:142-3. LinkGoogle Scholar2. Moser K. Venous thromboembolism. Am Rev Respir Dis. 1990;141:235-49. CrossrefMedlineGoogle Scholar3. BounameauxCiraficide Moerloose HPP. Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism. Lancet. 1991;1:196-200. CrossrefGoogle Scholar4. . Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Affairs Medical Center Portland, OR 97207 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDiagnostisches Vorgehen bei Verdacht auf Lungenembolie 15 April 1991Volume 114, Issue 8Page: 702-703KeywordsAngiographyLungsPulmonary embolismVentilation perfusion Issue Published: 15 April 1991 PDF downloadLoading ...
REGULATION OF PHOSPHOLIPASE C ISOZYMES BY RAS SUPERFAMILY GTPASES
Authors: T. Kendall Harden, John Sondek
Journal: The Annual Review of Pharmacology and Toxicology (2006)

The physiological effects of many extracellular stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid-signaling pathways. These signaling responses include the classically described conversion of PtdIns(4,5)P(2) to the Ca(2+)-mobilizing second messenger Ins(1,4,5)P(3) and the protein kinase C-activating second messenger diacylglycerol as well as alterations in membrane association or activity of many proteins that harbor phosphoinositide binding domains. Here we discuss how the family of PLCs elaborates a minimal catalytic core typified by PLC-delta to confer multiple modes of regulation on their phospholipase activities. Although PLC-dependent signaling is prominently regulated by direct interactions with heterotrimeric G proteins or tyrosine kinases, the existence of at least 13 divergent PLC isozymes promises a diverse repertoire of regulatory mechanisms for this class of important signaling proteins. We focus here on the recently realized and extensive regulation of inositol lipid signaling by Ras superfamily GTPases directly acting on PLC isozymes and conclude by considering the biological and pharmacological ramifications of this regulation.
Sustained release of VEGF through PLGA microparticles improves vasculogenesis and tissue remodeling in an acute myocardial ischemia–reperfusion model
Authors: Fabio R. Formiga, Beatriz Pelacho, Elisa Garbayo, Gloria Abizanda, Juan J. Gavira, Teresa Simon-Yarza, Manuel Mazo, Esther Tamayo, Carlos Jauquicoa, Carlos Ortiz-de-Solorzano
Journal: Journal of Controlled Release (2010)