tbuckley/cabot-search huggingface dataset:
Genetic Linkage of the <i>ACE</i> Gene to Plasma Angiotensin-Converting Enzyme Activity but Not to Blood Pressure
Authors: R. Kreutz, N. Hübner, D. Ganten, K. Lindpaintner
Journal: Circulation (1995)

Background An allelic variant of the ACE gene has been found to be linked to plasma angiotensin-converting enzyme (ACE) activity in humans and has been implicated in the etiology of some common cardiovascular disorders. Previously, we have shown significant genetic linkage of blood pressure to a region on rat chromosome 10 that contains ACE in an experimental F 2 -intercross between the stroke-prone spontaneously hypertensive rat (SHRSP HD ) and the normotensive Wistar-Kyoto (WKY HD -0) reference strain. Subsequent investigations revealed marked differences in plasma ACE activity among the SHRSP HD and WKY HD -0 strains. Nonetheless, the physiological relevance of these findings remained obscure. We therefore investigated the genetic determination of plasma ACE activity and its relation to blood pressure and dietary NaCl exposure in a model of experimental genetic hypertension, the SHRSP HD . Methods and Results We conducted a further crossbreeding experiment between SHRSP HD and a congenic reference strain, WKY HD -1, that carries a 6-centimorgan (cM) long, SHRSP-homologous segment introgressed in chromosome 10, 26 cM remote from ACE . This allowed us to contrast effects on blood pressure and ACE activity conferred by the ACE locus with other more remote loci within the congenic chromosomal region. Genetic analysis in this F 2 (WKY HD -1×SHRSP HD ) cross revealed that plasma ACE activity was determined almost entirely by genetic effects of the ACE gene locus (lod score=43). However, neither plasma ACE nor the ACE locus showed any cosegregation with blood pressure before or after dietary NaCl exposure. Conclusions These results demonstrate that a molecular variant of the ACE gene determines plasma ACE activity but exhibits no direct effect on blood pressure. Moreover, the findings also exclude the possibility that plasma ACE is secondarily affected by blood pressure or excess dietary NaCl exposure. Our results reconcile the previous discrepancy between findings in human and experimental hypertension.
Defective peroxisomal proliferators activated receptor gamma activity due to dominant‐negative mutation synergizes with hypertension to accelerate cardiac fibrosis in mice
Authors: Adrienn Kis, Colin Murdoch, Min Zhang, Anjana Siva, Sergio Rodriguez‐Cuenca, Stefania Carobbio, Agnes Lukasik, Margaret Blount, Steve O'Rahilly, Sarah L. Gray, Ajay M. Shah, Antonio Vidal‐Puig
Journal: European Journal of Heart Failure (2009)

Humans with inactivating mutations in peroxisomal proliferators activated receptor gamma (PPARgamma) typically develop a complex metabolic syndrome characterized by insulin resistance, diabetes, lipodystrophy, hypertension, and dyslipidaemia which is likely to increase their cardiovascular risk. Despite evidence that the activation of PPARgamma may prevent cardiac fibrosis and hypertrophy, recent evidence has suggested that pharmacological activation of PPARgamma causes increased cardiovascular mortality. In this study, we investigated the effects of defective PPARgamma function on the development of cardiac fibrosis and hypertrophy in a murine model carrying a human dominant-negative mutation in PPARgamma.Mice with a dominant-negative point mutation in PPARgamma (P465L) and their wild-type (WT) littermates were treated with either subcutaneous angiotensin II (AngII) infusion or saline for 2 weeks. Heterozygous P465L and WT mice developed a similar increase in systolic blood pressure, but the mutant mice developed significantly more severe cardiac fibrosis to AngII that correlated with increased expression of profibrotic genes. Both groups similarly increased the heart weight to body weight ratio compared with saline-treated controls. There were no differences in fibrosis between saline-treated WT and P465L mice.These results show synergistic pathogenic effects between the presence of defective PPARgamma and AngII-induced hypertension and suggest that patients with PPARgamma mutation and hypertension may need more aggressive therapeutic measures to reduce the risk of accelerated cardiac fibrosis.
A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarray immunoassay
Authors: Jing Lin, Francesca M. Bruni, Zhiyan Fu, Jennifer Maloney, Ludmilla Bardina, Attilio L. Boner, Gustavo Gimenez, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2012)
Cetuximab in Advanced Non-Small Cell Lung Cancer
Authors: Ramaswamy Govindan
Journal: Clinical Cancer Research (2004)

The epidermal growth factor receptor (EGFR) is frequently overexpressed in non-small cell lung cancer (NSCLC). EGFR activation results in phosphorylation of several downstream intracellular substrates involved in cell proliferation, angiogenesis, and inhibition of apoptosis. Cetuximab (C225, Erbitux), a monoclonal antibody directed against ligand binding in the extracellular domain of EGFR, inhibits tumor growth and is synergistic with chemotherapy and radiation. Cetuximab has been studied in combination with chemotherapy in previously untreated metastatic NSCLC. The response rates in preliminary reports range from 29% to 53%. In patients with refractory/recurrent NSCLC, the combination of docetaxel and cetuximab resulted in a promising response rate of 28%, higher than the typical response rates seen with docetaxel monotherapy in this setting. Addition of cetuximab to chemotherapy is generally well tolerated. Molecular mechanisms predicting response to cetuximab therapy are currently not well understood. Studies are ongoing to assess the single-agent activity of cetuximab in metastatic NSCLC.
New and Important Pharmaceutic Product.
Authors: E. C. Mann
Journal: JAMA (1894)

New York, November, 1894. <h3>To the Editor:</h3> —On July 28, last, we presented to the members of the medical profession through the columns of theJournal, a new brain and nerve tissue chemic food. The glycero-acid phosphate, the formula of which is almost identical with that of the lecithin of the brain cell and nerve tissue, C<sub>44</sub>H<sub>90</sub>NPO<sub>9</sub>; and which furnishes the proper chemic nerve cell and nerve tissue food to the vesicular neurine of the brain where nervous force is generated, and to the tubular or fibrous neurine which conducts it. In answer to numerous inquiries and requests for samples I have sent to all who requested it, a sample of this nerve food with the result that it is now in successful use in many of our hospitals with good clinical results. For many years I have felt the necessity for a preparation of
Renin angiotensin system-dependent hypertrophy as a contributor to heart failure in hypertensive rats: different characteristics from renin angiotensin system-independent hypertrophy
Authors: Yasushi Sakata, Tohru Masuyama, Kazuhiro Yamamoto, Reiko Doi, Toshiaki Mano, Tsunehiko Kuzuya, Takeshi Miwa, Hiroshi Takeda, Masatsugu Hori
Journal: Journal of the American College of Cardiology (2001)
Evaluation of the efficacy and safety of etoricoxib in the treatment of hemophilic arthropathy
Authors: Christos Tsoukas, M. Elaine Eyster, Sumiko Shingo, Saurabh Mukhopadhyay, Karen M. Giallella, Sean P. Curtis, Alise S. Reicin, Agustin Melian
Journal: Blood (2005)
Aspects cliniques et endoscopiques de l'atteinte oesophagienne au cours de la sclérodermie systémique. A propos de 183 observations
Authors: M Lahcene, N Oumnia, N Matougui, A Tebaibia, M Boudjella, B Touchene
Journal: Endoscopy (2008)

Objectif: Préciser les aspects cliniques et endoscopiques de l'atteinte œsophagienne de la sclérodermie systémique (SDS).
CORONARY COMPUTED TOMOGRAPHY FOR DETERMINATION OF THE SYNTAX SCORE IN PATIENTS WITH LEFT MAIN AND/OR 3-VESSEL CORONARY DISEASE: COMPARISON WITH INVASIVE ANGIOGRAPHY
Authors: Eduardo Pozo, Luis Alvarez-Acosta, David Alonso, Maria Eduarda Menezes de Siqueira, Pablo Pazos-Lopez, Adam Jacobi, Jagat Narula, Valentin Fuster, Javier Sanz
Journal: Journal of the American College of Cardiology (2014)
Generation of HIV-1 Resistant and Functional Macrophages From Hematopoietic Stem Cell–derived Induced Pluripotent Stem Cells
Authors: Amal Kambal, Gaela Mitchell, Whitney Cary, William Gruenloh, Yunjoon Jung, Stefanos Kalomoiris, Catherine Nacey, Jeannine McGee, Matt Lindsey, Brian Fury, Gerhard Bauer, Jan A Nolta, Joseph S Anderson
Journal: Molecular Therapy (2010)

Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. By developing iPSCs to treat HIV, there is the potential for generating a continuous supply of therapeutic cells for transplantation into HIV-infected patients. In this study, we have used human hematopoietic stem cells (HSCs) to generate anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into continuously growing iPSC lines with four reprogramming factors and a combination anti-HIV lentiviral vector containing a CCR5 short hairpin RNA (shRNA) and a human/rhesus chimeric TRIM5α gene. Upon directed differentiation of the anti-HIV iPSCs toward the hematopoietic lineage, a robust quantity of colony-forming CD133+ HSCs were obtained. These cells were further differentiated into functional end-stage macrophages which displayed a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages exhibited strong protection from HIV-1 infection. Here, we demonstrate the ability of iPSCs to develop into HIV-1 resistant immune cells and highlight the potential use of iPSCs for HIV gene and cellular therapies. Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. By developing iPSCs to treat HIV, there is the potential for generating a continuous supply of therapeutic cells for transplantation into HIV-infected patients. In this study, we have used human hematopoietic stem cells (HSCs) to generate anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into continuously growing iPSC lines with four reprogramming factors and a combination anti-HIV lentiviral vector containing a CCR5 short hairpin RNA (shRNA) and a human/rhesus chimeric TRIM5α gene. Upon directed differentiation of the anti-HIV iPSCs toward the hematopoietic lineage, a robust quantity of colony-forming CD133+ HSCs were obtained. These cells were further differentiated into functional end-stage macrophages which displayed a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages exhibited strong protection from HIV-1 infection. Here, we demonstrate the ability of iPSCs to develop into HIV-1 resistant immune cells and highlight the potential use of iPSCs for HIV gene and cellular therapies.
Transfusion and Anaemia
Authors: J. R. Bennett, D. C. James
Journal: BMJ (1965)

This study examined the role of radionuclide bone scanning in the early assessment of free autologous cancellous bone grafts in augmentation rhinoplasty and compared the failure rates of grafts taken from the calvaria and ilium. Twenty patients had three-phase bone scanning of the facial regions performed between 2 and 15 wk after rhinoplasty, and a comparison was made with the results of clinical assessment and X-ray findings 3 mo after surgery. Eleven patients had grafts taken from the calvaria and nine had iliac grafts. On lateral views, bone graft uptake of isotope, which was less than or equal to the adjacent soft tissue, was found in 2 out of 20 patients and this finding predicted subsequent graft failure as measured by clinical assessment and X-ray evidence of bone resorption. Both failures had grafts taken from the calvaria while none from the ilium failed. These failure rates, however, were not significantly different.
Subacute Bacterial Endocarditis at the University of Minnesota Hospitals, 1939-1959.
Authors: G. A. Pankey
Journal: Annals of Internal Medicine (1961)

s1 May 1961Subacute Bacterial Endocarditis at the University of Minnesota Hospitals, 1939-1959.G. A. Pankey, M.D.G. A. Pankey, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1056_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOne hundred sixty-seven patients with subacute bacterial endocarditis were observed at the University of Minnesota Hospitals from 1939 to 1959. Eleven patients had one recurrence and four had two recurrences. For analysis of clinical and laboratory data each recurrence was considered to be a separate patient, bringing the total number to 186. The disease was defined as a bacterial endocarditis of greater than 50 days' duration associated for the most part with a micro-organism of low virulence, resulting in clinical signs of chronic infection.There were 85 males and 82 females. Thirty per cent were under 21 and 25% were... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Minneapolis, Minn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1056-1057KeywordsBacterial diseasesClinical laboratoriesEndocarditisInfectious diseasesResearch laboratories ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
IS SCARLET FEVER A STREPTOCOCCUS DISEASE?
Authors: LUDVIG HEKTOEN
Journal: JAMA (1907)

Since the earliest application of microbiological methods to the study of scarlet fever the streptococcus has claimed the lion's share of attention. Its significance has grown as the observations have extended. At present the streptococcus is held by some to be the actual cause of the disease, while others, and I think the majority, look on it as essentially a secondary invader on which, however, depends to a large extent the fate of the patient. For the purpose of discussing this question it is necessary first of all to consider the occurrence and the distribution of streptococci in scarlet fever. Numerous investigations<sup>1</sup>have indicated that streptococci occur on the tonsils of scarlet fever in far greater abundance than in health. In his study of the bacteria of the throat and skin in scarlet fever Weaver calls special attention to the enormous numbers of streptococci in the throat in this
Psychophysiological Personality Patterns of Hypertensive and Normotensive Subjects
Authors: Elisabeth Richter-Heinrich
Journal: Psychotherapy and Psychosomatics (1970)

1. It is possible to use a psychophysiological stress procedure with appropriate statistical treatment as a screening test to differentiate between normotensive and hypertensive groups. 2. The inclusion of psychological and sensory variables improves the discrimination of the groups and indicates psychophysiological correlations, which only by means of multivariate analysis become evident.
A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia
Authors: OA Bernard, M Busson-LeConiat, P Ballerini, M Mauchauffé, V Della Valle, R Monni, F Nguyen Khac, T Mercher, V Penard-Lacronique, P Pasturaud, L Gressin, R Heilig, M-T Daniel, M Lessard, R Berger
Journal: Leukemia (2001)
Letter by Struthers et al Regarding Article, “Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function”
Authors: Allan D. Struthers, Chim C. Lang
Journal: Circulation (2006)

To the Editors:We read with interest the article by Kathiresan et al, 1 who showed that natriuretic peptides were the only biomarker independently related to endothelial function.The authors appear to imply, especially in their Clinical Perspective on page 945, that their results may be the result of natriuretic peptides influencing endothelial function.We feel that 2 other possible explanations for their finding are more likely.We previously showed in patients with diabetes that B-type natriuretic peptide (BNP) increases as the augmentation index increases. 2This suggests that stiff arteries/arterioles could increase afterload and subtly increase intracardiac pressure and thus natriuretic peptides.Endothelial dysfunction tracks with stiff arteries/arterioles.A second possible explanation is that endothelial dysfunction may be a sign of early atherosclerosis in a wide variety of blood vessels, including the coronary vessels.In turn, coronary atherosclerosis could produce myocardial ischemia.In fact, myocardial tissue that is injured in any way such as by ischemia appears to express and release more BNP than noninjured or nonischemic myocardial tissue, irrespective of hemodynamic considerations. 3,4Thus, endothelial dysfunction could imply subtle but asymptomatic myocardial ischemia that is identifiable by a subtly elevated natriuretic peptide level.In fact, we recently showed that subtle elevations in BNP are indicative of silent myocardial ischemia in type 2 diabetics. 5We feel some combi-nation of the above mechanisms is the likely explanation for the interesting observation from Kathiresan et al.
The significance of intramammary lymph node metastases in breast cancer management.
Authors: BV Hogan, MB Peter, HG Shenoy, KM Horgan, AM Shaaban
Journal: Cancer Research (2009)

Abstract Abstract #1009 Introduction &amp;#x2028; Intramammary lymph nodes are defined as lymph nodes surrounded by breast tissue. They are a potential site of regional spread for breast cancer and metastases in this node is reported in up to 9.8% of operable breast cancers. Despite this, the existence of the intramammary node is not widely appreciated and the clinical significance of intramammary nodal metastases remains uncertain. The aim of this study is to determine the prognostic relevance of intramammary lymph node metastases and how it impacts on current breast cancer treatment modalities.&amp;#x2028; Methods&amp;#x2028; All patients with cytologically or histologically proven intramammary nodes were identified from the pathology database at the Leeds Teaching Hospitals. A total of 102 specimens were identified in 100 patients with a primary breast malignancy over a 13 year period (1994-2007). Clinical data including information on recurrences and death was obtained from patient records.&amp;#x2028; Results&amp;#x2028; One hundred patients were identified on our pathology database to have intramammary lymph nodes in association with a primary breast cancer. Ten were identified pre-operatively on breast imaging and 90 were first discovered on pathological assessment of excised breast tissue. Twenty one contained metastases. Factors that predicted for intramammary node metastases were lymphovascular invasion (p=0.002) and grade of tumour (p=0.012). The presence of metastases within the intramammary lymph node was associated with a poorer disease free survival (p=0.0072) and reduced overall survival (p=0.0128) at a mean follow up of 34.7 months. Sixty seven percent of patients with intramammary node metastases had further axillary metastases. In no case was the intramammary node identified as the sentinel node. One patient had an intramammary node metastases but benign axillary sentinel node. An axillary node clearance was not performed and she presented 19 months later with an axillary nodal recurrence.&amp;#x2028; Conclusion&amp;#x2028; The presence of intramammary lymph node metastases is associated with poorer outcome in breast cancer patients. Pre-operative detection of intramammary lymph node metastases is helpful to guide breast and axillary surgery. With the use of lymphoscintigraphy intramammary nodes will be increasingly identified as the sentinel node. Intramammary lymph node metastases predicts strongly for axillary metastatic disease and axillary node clearance should be recommended even when it is associated with a benign axillary sentinel node biopsy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1009.
F-18 FDG PET/CT Scan in Biliary Cystadenocarcinoma
Authors: Kentaro Takanami, Tomohiro Kaneta, Shogo Yamada, Shoki Takahashi
Journal: Clinical Nuclear Medicine (2009)

A 72-year-old woman was referred to the hospital due to a cystic tumor in the liver. F-18 FDG PET/CT demonstrated intense uptake in the marginal parenchymal region of the cystic tumor in the left lobe of the liver. Subsequently an extended left hepatectomy was performed. The histopathological findings demonstrated biliary cystadenocarcinoma. FDG/PET may thus contribute to the diagnosis of malignant cystic tumors in the liver.
Structure and Biosynthesis of Pro-Adrenocorticotropin/Endorphin and Related Peptides*
Authors: BETTY A. EIPPER, RICHARD E. MAINS
Journal: Endocrine Reviews (1980)

THIS REVIEW will deal with the biosynthesis of many of the members of the ACTH/lipotropin (LPH) family of peptides (Fig. 1). Peptides in this family fall into two groups: peptides related to ACTH include α-melanotropin (αMSH) and corticotropin-like intermediate lobe peptide (CLIP); peptides related to βLPH include γLPH, βMSH, and β-endorphin. In several species ACTH and βLPH each contain an identical heptapeptide segment located in the region of the molecule that is responsible for melanotropic bioactivity (1, 2). In this review we have taken a somewhat historical approach, and will therefore begin with a discussion of the biosynthesis of ACTH and the characterization of biosynthetic precursors to ACTH. When this work began, βLPH, γLPH, and βMSH were well-characterized pituitary peptides, but the opioid peptides (and β-endorphin in particular) had not yet been identified (3–5). Studies on the biosynthesis of ACTH were heavily influenced by prior work defining the biosynthetic pathways for insulin and parathyroid hormone (PTH) (9, 10). By describing the reasoning and experimental approaches that were helpful in investigating ACTH biosynthesis we hope to provide information that may be useful in studying the biosynthesis of some of the many small bioactive peptides of the brain and gut.