tbuckley/cabot-search huggingface dataset:
Cardiovascular Phenotype of a Mouse Strain With Disruption of Bradykinin B <sub>2</sub> -Receptor Gene
Authors: Paolo Madeddu, Maria Vittoria Varoni, Domenico Palomba, Costanza Emanueli, Maria Piera Demontis, Nicola Glorioso, Paolo Dessı̀-Fulgheri, Riccardo Sarzani, Vittorio Anania
Journal: Circulation (1997)

Background To evaluate the role of kinins in the regulation of cardiovascular function, we studied the phenotype of a mouse strain with disruption of the bradykinin B 2 -receptor gene (Bk 2r −/− ). Methods and Results Under basal conditions, tail-cuff blood pressure was higher in Bk2r −/− than in wild-type Bk2r +/+ and heterozygous Bk2r +/− mice (124±1 versus 109±1 and 111±2 mm Hg, respectively; P&lt;.01 for both comparisons), a difference that was confirmed by measurements of intra-arterial blood pressure in unanesthetized mice. Heart weight was greater in Bk2r −/− than in Bk2r +/+ and Bk2r +/− mice (505±10 versus 449±12 and 477±10 mg/100 g body wt, P&lt;.05). Chronic blockade of B 2 -receptors by Icatibant (50 nmol/100 g body wt twice a day SC) or inhibition of nitric oxide synthase by nitro- l -arginine-methyl ester (0.14 mmol/100 g body wt orally) increased the blood pressure of Bk2r +/+ to the levels of Bk2r −/− mice. Compared with the wild-type strain, both Bk2r −/− and Bk2r +/− mice showed exaggerated vasopressor responses to angiotensin II. In addition, chronic administration of an angiotensin AT 1 -receptor antagonist reduced the basal blood pressure of Bk2r −/− by 21±3 mm Hg (P&lt;.05) to the levels of Bk2r +/+ . No difference was detected between strains as far as plasma renin activity and the expression of renin and AT 1 -receptor genes are concerned. Chronic salt loading (0.84 mmol/g chow for 15 days) increased the blood pressure of Bk2r −/− and Bk2r +/− by 34±3 and 14±6 mm Hg, respectively, whereas it was ineffective in Bk2r +/+ . Conclusions Our results suggest that a normally functioning B 2 -receptor is essential for the maintenance of cardiovascular homeostasis in mice. Dysfunction of the kallikrein-kinin system could contribute to increase blood pressure levels by leaving the activity of vasoconstrictor agents unbalanced.
Crohn's Disease and its Consequences
Authors: J. W. Paulley
Journal: BMJ (1970)

SIR,-Your leading article on Crohn's Disease and its Consequences (11 April p. 65) says "Psychological factors are gener- ally held not to be aetiologically important" and cites to support such a "generally held" view but one reference, and that to an article which has been much criticised on account of its methodology.Dare I suggest that such selectivity if practised by psychiatrists would quite prop- erly call down the wrath of medical science?To redress the balance I draw your atten- tion to a few recent articles giving the opposite view.'-'-I am, etc.,
1069-119 Predictors of mortality in patients hospitalized with worsening heart failure: Insights from the ACTIV in CHF trial
Authors: Christopher M O'Connor, Kirkwood F Adams, Wendy A Gattis, Alejandro Barbagelata, Uri Elkayam, Frank Mc Grew, Jalal Ghali, Raymond Benza, Marc Klapholz, John Ouyang, Cesare Orlandi, Mihai Gheorghiade
Journal: Journal of the American College of Cardiology (2004)
258. CNS-Directed Antioxidant Enzyme Delivery: Protecting Neurons from Oxidative Stress and Apoptosis Induced by HIV-1
Authors: Tat Lokesh Agrawal, Jean-pierre Louboutin, David S. Strayer
Journal: Molecular Therapy (2006)

Oxidant stress-induced neuron apoptosis is a feature of many diseases affecting the CNS, including stroke, Alzheimer's disease and others. HIV-1 Tat is a soluble protein that induces neuronal apoptosis and is felt to play a critical role in HIV-1 induced CNS disease. Tat causes disruption of calcium homeostasis, increased production of reactive oxygen species (ROS) with consequent oxidative stress and apoptosis. We tested whether the anti-oxidant enzymes superoxide-dismutase (SOD1) or glutathione peroxidase (GPx1) delivered by rSV40 vectors could be used to mitigate HIV-1 Tat-induced neurotoxicity. Both enzymes detoxify oxygen free radicals. NT-2 derived neurons and primary neurons were transduced either with rSV40s carrying each transgene individually or in combination, first with one vector then the other. Post-transduction, cells were challenged with HIV-1 Tat. Apoptosis was measured by TUNEL assay. Cytosolic calcium was measured by split-beam photometry after preloading cells with FURA-2AM. Transduction with SOD1- and GPX1-carrying vectors provided excellent transgene expression (>90%), as assessed by Western blotting, direct assays of enzyme activity and immunostaining. Tat- induced maximal apoptosis at a concentration of 100 ng/ml at 6 hours, and showed a linear dose-response relationship. Neuronal cells transduced singly with either of the vectors, SV(SOD1) or SV(GPx1), were not protected from Tat-induced apoptosis. Interestingly, when doubly transduced cells were challenged with Tat they were >90% protected from apoptosis. Exposing neurons to Tat increased cytosolic free calcium. The patterns of protection from Tat-induced apoptosis were seen in these studies as well: intracellular Ca2+ release stimulated by Tat was not affected by single transduction. However, cells doubly transduced with both anti-oxidant enzymes were protected from Tat-induced calcium overload. These findings suggest that Tat-induced calcium fluxes are signaled via two different pathways involving ROS. We have therefore shown that SV40 vectors carrying anti-oxidant transgenes can protect neuronal cells from HIV-1 Tat-induced apoptosis. Gene therapy using these vectors may thus be useful in mitigating ROS-related neurotoxicity as is seen in HIV-1 encephalopathy and other CNS diseases.
Distinct Effects of Ligand-Induced PDGFRα and PDGFRβ Signaling in the Human Rhabdomyosarcoma Tumor Cell and Stroma Cell Compartments
Authors: Monika Ehnman, Edoardo Missiaglia, Erika Folestad, Joanna Selfe, Carina Strell, Khin Thway, Bertha Brodin, Kristian Pietras, Janet Shipley, Arne Östman, Ulf Eriksson
Journal: Cancer Research (2013)

Abstract Platelet-derived growth factor receptors (PDGFR) α and β have been suggested as potential targets for treatment of rhabdomyosarcoma, the most common soft tissue sarcoma in children. This study identifies biologic activities linked to PDGF signaling in rhabdomyosarcoma models and human sample collections. Analysis of gene expression profiles of 101 primary human rhabdomyosarcomas revealed elevated PDGF-C and -D expression in all subtypes, with PDGF-D as the solely overexpressed PDGFRβ ligand. By immunohistochemistry, PDGF-CC, PDGF-DD, and PDGFRα were found in tumor cells, whereas PDGFRβ was primarily detected in vascular stroma. These results are concordant with the biologic processes and pathways identified by data mining. While PDGF-CC/PDGFRα signaling associated with genes involved in the reactivation of developmental programs, PDGF-DD/PDGFRβ signaling related to wound healing and leukocyte differentiation. Clinicopathologic correlations further identified associations between PDGFRβ in vascular stroma and the alveolar subtype and with presence of metastases. Functional validation of our findings was carried out in molecularly distinct model systems, where therapeutic targeting reduced tumor burden in a PDGFR-dependent manner with effects on cell proliferation, vessel density, and macrophage infiltration. The PDGFR-selective inhibitor CP-673,451 regulated cell proliferation through mechanisms involving reduced phosphorylation of GSK-3α and GSK-3β. Additional tissue culture studies showed a PDGFR-dependent regulation of rhabdosphere formation/cancer cell stemness, differentiation, senescence, and apoptosis. In summary, the study shows a clinically relevant distinction in PDGF signaling in human rhabdomyosarcoma and also suggests continued exploration of the influence of stromal PDGFRs on sarcoma progression. Cancer Res; 73(7); 2139–49. ©2013 AACR.
Postprandial Blood Glucose Predicts Cardiovascular Events and All-Cause Mortality in Type 2 Diabetes in a 14-Year Follow-Up
Authors: Franco Cavalot, Andrea Pagliarino, Manuela Valle, Leonardo Di Martino, Katia Bonomo, Paola Massucco, Giovanni Anfossi, Mariella Trovati
Journal: Diabetes Care (2011)

To evaluate whether postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a long-term follow-up taking into account A1C and the main cardiovascular risk factors.Consecutive type 2 diabetic patients (n = 505) followed up at our diabetes clinic were evaluated at baseline (1995) for the main cardiovascular risk factors and for five glycemic control parameters (fasting blood glucose, blood glucose 2 h after breakfast, blood glucose 2 h after lunch, blood glucose before dinner, and A1C); all-cause mortality and the first cardiovascular events occurring during the 14-year follow-up were measured.We observed 172 cardiovascular events (34.1% of the population) and 147 deaths (29.1% of the population). Using the Cox analysis with the backward method, we categorized the variables according to the therapeutic targets of the American Diabetes Association. Our observations were as follows. When the five glycemic control parameters were considered together, the predictors were 1) for cardiovascular events, blood glucose 2 h after lunch (hazard ratio 1.507, P = 0.010) and A1C (1.792, P = 0.002); and 2) for mortality, blood glucose 2 h after lunch (1.885, P < 0.0001) and A1C (1.907, P = 0.002). When blood glucose 2 h after lunch and A1C were considered together with the main cardiovascular risk factors, the following glycemic control parameters were predictors: 1) for cardiovascular events, blood glucose 2 h after lunch (1.452, P = 0.021) and A1C (1.732, P = 0.004); and 2) for mortality, blood glucose 2 h after lunch (1.846, P = 0.001) and A1C (1.896, P = 0.004).In type 2 diabetes, both postprandial blood glucose and A1C predict cardiovascular events and all-cause mortality in a long-term follow-up.
The Effect of the Valsalva Maneuver on the Circulation
Authors: E. ELISBERG, E. SINGIAN, G. MILLER, L. N. KATZ
Journal: Circulation (1953)

The normal response following sustained straining, as in a Valsalva maneuver, is a rise in systemic arterial pressure and a reflex slowing of the heart rate. This response was found to be abolished in some patients with mitral stenosis, with organic heart disease, with pulmonary vascular disease (including kyphoscoliosis), or with congenital heart disease. It was abolished in all three instances of pericardial disease studied. The relationship of the presence or absence of a poststraining bradycardia to cardiovascular dynamics at rest and on exercise as determined by right heart catheterization is presented, and the suggestion is made that the Valsalva maneuver, when performed under electrocardiographic control, may be a simple, dynamic stress test of the circulation. This suggestion is waiting for further exploration.
Bundling Informed Consent and Advance Care Planning in Chronic Cardiovascular Disease
Authors: James N. Kirkpatrick, Paul J. Hauptman, Sarah J. Goodlin
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia
Authors: Francesco Fazi, Giuseppe Zardo, Vania Gelmetti, Lorena Travaglini, Alberto Ciolfi, Luciano Di Croce, Alessandro Rosa, Irene Bozzoni, Francesco Grignani, Francesco Lo-Coco, Pier Giuseppe Pelicci, Clara Nervi
Journal: Blood (2007)
Bone Marrow in Lupus Erythematosus
Authors: EDWARD CHIRITO
Journal: Annals of Internal Medicine (1977)

Comments1 June 1977Bone Marrow in Lupus ErythematosusEDWARD CHIRITO, M.D.EDWARD CHIRITO, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-6-831_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The review article "Hematologic Aspects of Systemic Lupus Erythematosus" by Budman and Steinberg (Ann Intern Med86:220-229, 1977) omits mention of the bone marrow as a target organ in the disease. Rosen and associates (1) have reported five patients with the bone-marrow morphologic features of myelofibrosis in association with the lupus erythematosus cell phenomenon. In addition, all five had antinuclear antibodies in the serum, and two had a positive direct antiglobulin reaction (Coombs' Test). Clinically, four were female, four had unexplained fever, and two arthralgia. Only one patient was under age 50 and none manifested the classical...Reference1. ROSEN J, CRAMER A, DUBOIS E, and LUKES R: Systemic lupus erythematosus (SLE) and myelofibrosis: a possible pathogenetic relationship, Clinical Research 21:565, 1973 Google Scholar1. CASSILETH P and MYERS A: Erythroid aplasia in systemic lupus erythematosus. Am J Med 55:706-710, 1973 CrossrefMedlineGoogle Scholar2. KRANTZ S, MOORE W, and ZOENTZ S: Studies on pure red cell aplasia. V. Presence of erythroblast cytotoxicity in yG-globulin fraction of plasma. J Clin Invest 52:324-336, 1973 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: EDWARD CHIRITO, M.D.Affiliations: Department of Physiology McGill University Montreal. PQ H3C 3G1 Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1977Volume 86, Issue 6 Page: 831-832 Keywords Antinuclear antibodies Arthralgia Bone marrow Fevers Lupus erythematosus Systemic lupus erythematosus ePublished: 1 December 2008 Issue Published: 1 June 1977 PDF downloadLoading ...
Community acquired lobar pneumonia in patients with HIV infection and AIDS.
Authors: R F Miller, N M Foley, D Kessel, A A Jeffrey
Journal: Thorax (1994)

Community acquired bacterial pneumonia is increasingly encountered in HIV infected individuals and some patients have a radiographic lobar pneumonia.A retrospective review of clinical features, microbiological diagnosis, and outcome of community acquired lobar pneumonia was carried out in HIV positive patients admitted to a specialist unit from 1987 to 1993.Forty nine episodes occurred in 45 patients, all of whom were men. CD4 counts ranged widely. A bacteriological diagnosis was made in 25 episodes (51%), seven patients had more than one infective cause. The commonest pathogens were Streptococcus pneumoniae (11 episodes), Staphylococcus aureus (six), Pneumocystis carinii (three), Haemophilus influenzae (three), and Pseudomonas aeruginosa (two). Four patients died. Other complications included intrapulmonary cavitation or abscess formation (11 episodes), empyema (three), and pleural effusion (10 episodes).Many different infections cause community acquired lobar pneumonia in HIV positive men. Some patients have co-infections and there is a high complication rate.
Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients
Authors: S Schnittger, U Bacher, C Haferlach, W Kern, T Haferlach
Journal: Leukemia (2007)
Periodic Apnea, Exercise Hypoventilation, and Hypothalamic Dysfunction
Authors: MICHAEL A. MOSKOWITZ
Journal: Annals of Internal Medicine (1976)

Periodic apnea and exercise hypoventilation were observed in a 14-year-old boy. Hyperphagia, obesity, serum hyperosmolality without diabetes insipidus or appropriate thirst, and retardation of growth and sexual development indicated a hypothalamic disorder. Neurologic evaluation was normal except for electroencephalographic changes induced by apnea. Pulmonary function tests, resting arterial blood gases in the wakeful state, and ventilatory response to inhaled CO2 were also normal. Acute hypoxemia and respiratory acidosis occurred with apnea during sleep and with insufficient ventilation during exercise. The central origin of sleep apneas was shown by esophageal pressure monitoring. The hypothalamic dysfunction and exercise hypoventilation distinguish this patient from others with obesity and periodic apnea.
A New Paradigm for Plaque Stabilization
Authors: John A. Ambrose, Eulogio E. Martinez
Journal: Circulation (2002)

The concept of plaque stabilization was developed to explain how lipid lowering could decrease adverse coronary events without a substantial reduction in the regression of atherosclerosis. Plaques were stabilized by reducing serum cholesterol leading to several favorable pathobiological changes in the vessel wall of lipid-rich plaques responsible for a majority of acute coronary events. However, this concept is limited for several reasons including that it does not incorporate strategies directed against either plaques that have already destabilized or non-lipid-rich plaques, which are the substrate for at least one third of major coronary thrombi and may or may not be stabilized by lipid lowering. For the destabilized plaque with overlying thrombus, either percutaneous intervention, long-term antithrombotic and/or anticoagulant therapy, or possibly aggressive lipid lowering stabilizes lesions by reducing subsequent thrombosis at the lesion site and, at least with lipid lowering, by improving endothelial function and possibly reducing inflammation. Short-term, in-hospital antithrombotic approaches alone with agents like the GP platelet IIb/IIIa inhibitors have not been effective in this situation. For other plaques not presently destabilized, the main goal of therapy is reducing future acute coronary events. Several classes of drugs, including ACE inhibitors, beta-blockers, and antithrombotic agents in addition to lipid-lowering agents, reduce events, and this may be attributable, at least in part, to plaque-stabilizing effects.
261 LONG-TERM SORAFENIB EXPOSURE IN HEPATOCELLULAR CANCER CELL LINES: RESISTANCE, RISK OF REBOUND GROWTH AND EPITHELIAL TO MESENCHYMAL TRANSITION
Authors: H. van Malenstein, C. Verslype, P. Windmolders, L. Libbrecht, F. Nevens, J. van Pelt
Journal: Journal of Hepatology (2011)
Burkitt's Tumor
Authors: PAUL P. CARBONE
Journal: Annals of Internal Medicine (1969)

Burkitt's tumor is a malignant neoplasm of predominantly undifferentiated lymphoreticular cells. Malignant lymphoma of this cell type usually occurs in children, has a characteristic anatomic distribution, and cytologically can be differentiated from acute lymphoblastic leukemia and poorly differentiated lymphoma of the histiocytic or lymphocytic type. Patients with Burkitt's tumor in Africa and the United States were studied on a common protocol. The patients in Africa often had localized jaw tumors while American patients had generalized disease with bone marrow and abdominal involvement. The response to cyclophosphamide was dramatic and persistent in both groups of patients. Immunologic deficiencies of antibody production and immune globulin levels were seen in both groups. Serologic studies indicated high titers of anti-herpes-like virus antibody in African Burkitt's tumor and in infectious mononucleosis patients. Titers in American patients with Burkitt's tumor were only moderately elevated.
Pathophysiology of Congenital Heart Disease
Authors: Mary Allen Engle
Journal: JAMA (1970)

From the planning of the conference on pathophysiology of congenital heart disease to the design of the cover, this book represents the work of experts. It is in response to the question, "Where have we been and where are we going?" The editors noted with admiration the tremendous advances of the recent past in the diagnosis and management of patients with congenital heart disease and then addressed themselves to what the future holds in the way of filling gaps in knowledge and developing new directions of research. In July 1967, they assembled in a conference 33 of the leading investigators in the fields of cardiovascular physiology, teratology, and instrumentation. They came chiefly from the west coast and east coast of the United States and from West Germany. The subjects of the studies they reported in the 28 chapters of this book range from chick embryos through ewes, Alaskan huskies, to
Neurologic Disease Associated with<i>Mycoplasma pneumoniae</i>Pneumonitis
Authors: ARNOLD S. BAYER
Journal: Annals of Internal Medicine (1981)

Several neurologic syndromes (including Guillain-Barré) complicated Mycoplasma pneumoniae pneumonitis in a young man. At onset of neurologic disease, buffy coat and cerebrospinal fluid cultures on inert media were negative for M. pneumoniae. However, metabolically active mycoplasma were identified in both body fluids by enhanced uptake of 14C-uracil versus 3H-uridine, with marked reduction in normal uridine-to-uracil uptake ratios (> 1000:1) in tissue culture. Uridine-to-uracil ratios were 8.5:1 and 15:1 for buffy coat and cerebrospinal fluid, respectively. Indirect fluorescent antibody (FA) studies confirmed the species as M. pneumoniae. In convalescence, uridine-to-uracil ratios and FA studies of buffy coat normalized, indicating clearance of M. pneumoniae from blood. Cell lines inoculated with "convalescent" cerebrospinal fluid showed slightly increased uracil uptake, slightly decreased uptake ratios, and persistent FA staining of approximately 5% of cells, indicating incomplete clearance of M. pneumoniae. Immune complexes were undetectable in either buffy coat or spinal fluid. This indicates that certain M. pneumoniae-associated neurologic disorders may be related to direct neural infection and not immunologically mediated as has been suggested.
Wood-Pulp Workers' Disease: A Hypersensitivity Pneumonitis Caused by Alternaria
Authors: DONALD P. SCHLUETER
Journal: Annals of Internal Medicine (1972)

Respiratory disease resulting from prolonged exposure to logs contaminated with Alternaria may be owing to a hypersensitivity reaction. Two patients had heavy and prolonged exposure to this mold during the manufacture of wood pulp. Their exposure led to recurrent episodes of chills, fever, and dyspnea that were followed by irreversible alterations in pulmonary function. Lung biopsy specimens showed changes compatible with a hypersensitivity pneumonitis. An inhalation challenge with an extract of Alternaria reproduced the clinical features of their disease.