tbuckley/cabot-search huggingface dataset:
The Humors
Authors: John W. Draper
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect of Graded Hypoxia on the Induction and Function of Inducible Nitric Oxide Synthase in Rat Mesangial Cells
Authors: Stephen L. Archer, Kimberly A. Freude, Pamela J. Shultz
Journal: Circulation Research (1995)

Abstract Inducible nitric oxide synthase (iNOS) catalyzes the formation of nitric oxide (NO) from l -arginine and O 2 . Although some O 2 is required for this reaction, it is uncertain whether biologically relevant levels of hypoxia alter this pathway. We examined the effects of graded hypoxia on several steps in the iNOS pathway in lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells: induction of iNOS mRNA, NO synthesis, NO oxidation to nitrite (NO 2 − ) and nitrate (NO 3 − ), and accumulation of cGMP. Cultured cells were incubated for 24 hours in airtight flasks containing O 2 (21%, 10%, 2.5%, and 0%), CO 2 (5%), and N 2 (balance), resulting in media P o 2 levels of 140±3, 85±1, 46±3 (moderate hypoxia), and 32±5 (severe hypoxia) mm Hg, respectively. During normoxia (P o 2 , 85 to 140 mm Hg) LPS increased iNOS mRNA with associated increases in NO synthesis, NO 2 − and NO 3 − accumulation, and intracellular cGMP levels. In the absence of LPS, there was minimal NO synthesis and no detectable iNOS mRNA. Even during severe hypoxia, LPS elevated NO 2 − and NO 3 − relative to levels in unstimulated cells ( P &lt;.05), although to a lesser extent than during normoxia ( P &lt;.05). The induction of iNOS mRNA by LPS was preserved in hypoxia, and intracellular cGMP levels were similar at all levels of oxygen tension, indicating that iNOS induction and function were not altered by moderate or severe hypoxia. However, moderate hypoxia did alter the partitioning and oxidation of NO, favoring the appearance of NO in the “headspace” (defined as the gas overlying the cells) and NO 3 − in the media. We conclude that although hypoxia can alter the partitioning and decomposition of NO, the induction of iNOS mRNA and the activity of its enzyme product are resistant to hypoxia (P o 2 , &gt;32 mm Hg).
Invariant NKT cell activation induces neutrophil accumulation and hepatitis: Opposite regulation by IL-4 and IFN-γ
Authors: Hua Wang, Dechun Feng, Ogyi Park, Shi Yin, Bin Gao
Journal: Hepatology (2013)

Alpha-Galactosylceramide (α-Galcer), a specific agonist for invariant natural killer T (iNKT) cells, is being evaluated in clinical trials for the treatment of viral hepatitis and liver cancer. However, the results from α-Galcer treatment are mixed, partially because of the variety of cytokines produced by activated iNKT cells that have an unknown synergistic effect on the progression of liver disease. It is well documented that injection of α-Galcer induces mild hepatitis with a rapid elevation in the levels of interleukin (IL)-4 and a delayed elevation in the levels of interferon-gamma (IFN-γ), and both of these cytokines are thought to mediate many functions of iNKT cells. Surprisingly, genetic deletion of both IL-4 and IFN-γ aggravated, rather than abolished, α-Galcer-induced iNKT hepatitis. Moreover, genetic ablation of IL-4, the IL-4 receptor, or its downstream signaling molecule signal transducer and activator of transcription (STAT)6 ameliorated α-Galcer-induced neutrophil infiltration, liver injury, and hepatitis. In contrast, genetic deletion of IFN-γ, the IFN-γ receptor, or its downstream signaling molecule STAT1 enhanced liver neutrophil accumulation, thereby exacerbating liver injury and hepatitis. Moreover, depletion of neutrophils eradicated α-Galcer-induced liver injury in wild-type, STAT1 knockout, and IFN-γ knockout mice.
COMPARISON OF FIVE YEARS CLINICAL OUTCOME OF DRUG–ELUTING STENT IMPLANTATION IN HIGH–ANGLED (&gt;70°) BIFURCATION AND LOWER–ANGLED (&lt;70°) BIFURCATION LESION OF UNPROTECTED LEFT MAIN CORONARY ARTERIES
Authors: Sunao Nakamura, Shotaro Nakamura, Hisao Ogawa, Hans Yeo, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Journal of the American College of Cardiology (2013)
Age and Outcome With Contemporary Thrombolytic Therapy
Authors: Harvey D. White, Gabriel I. Barbash, Robert M. Califf, R. John Simes, Christopher B. Granger, W. Douglas Weaver, Neal S. Kleiman, Philip E. Aylward, Joel M. Gore, Alec Vahanian, Kerry L. Lee, Allan M. Ross, Eric J. Topol
Journal: Circulation (1996)

Background Elderly patients with acute myocardial infarction have much to gain from reperfusion with thrombolytic therapy but are also at increased risk of adverse events. We examined outcomes according to age of patients receiving thrombolysis in an international trial. Methods and Results Patients were randomized to streptokinase plus subcutaneous heparin, streptokinase plus intravenous heparin, accelerated tissue plasminogen activator (TPA) plus intravenous heparin, or streptokinase and TPA plus intravenous heparin. Clinical outcomes at 30 days (death, stroke, and nonfatal, disabling stroke) and 1-year mortality were summarized descriptively for patients aged &lt;65 (n=24 708), 65 to 74 (n=11 201), 75 to 85 (n=4625), and &gt;85 years (n=412) and assessed as continuous functions of age. Older patients had a higher-risk profile with regard to baseline clinical and angiographic characteristics. Mortality at 30 days increased markedly with age (3.0%, 9.5%, 19.6%, and 30.3% in the four groups, respectively), as did stroke, cardiogenic shock, bleeding, and reinfarction. Combined death or disabling stroke occurred less often with accelerated TPA in all but the oldest patients, who showed a weak trend toward a lower incidence with streptokinase plus subcutaneous heparin: odds ratio 1.13; 95% confidence interval 0.6, 2.1. Similarly, accelerated TPA treatment resulted in lower 1-year mortality in all but the oldest patients (47% TPA versus 40.3% streptokinase). Conclusions Lower mortality and greater net clinical benefit were seen with accelerated TPA in patients aged ≤85 years. Because data are limited for patients aged &gt;85 years, the relative superiority of a given thrombolytic regimen cannot be determined. The interactions of stroke and mortality with newer thrombolytic strategies must be examined explicitly in older patients.
Death of the teaching autopsy: Summary of responses
Authors: B. Twisselmann
Journal: BMJ (2004)

<h3>Abstract</h3> Host-associated microbiomes are essential for a multitude of biological processes. Placed at the contact zone between external and internal environments, the little-studied oral microbiome has important roles in host physiology and health. Here we investigate the contribution of host evolutionary relationships and ecology in shaping the oral microbiome in three closely related gorilla subspecies (mountain, Grauer’s, and western lowland gorillas) using shotgun metagenomics of 46 museum-preserved dental calculus samples. We find that the oral microbiomes of mountain gorillas are functionally and taxonomically distinct from the other two subspecies, despite close evolutionary relationships and geographic proximity with Grauer’s gorillas. Grauer’s gorillas show intermediate bacterial taxonomic and functional, and dietary profiles. Altitudinal differences in gorilla subspecies ranges appear to explain these patterns, proposing a close connection between dental calculus microbiome and the environment, which is further supported by the presence of gorilla subspecies-specific phyllosphere/rhizosphere taxa. Mountain gorillas show high abundance of nitrate-reducing oral taxa, which may contribute to high altitude adaptation by modulating blood pressure. Our results suggest that ecology, rather than evolutionary relationships and geographic proximity, primarily shape the oral microbiome in these closely related species.
Systematic Analysis of Functional and Structural Changes After Coronary Microembolization: A Cardiac Magnetic Resonance Imaging Study
Authors: Frank Breuckmann, Kai Nassenstein, Christina Bucher, Ina Konietzka, Gernot Kaiser, Thomas Konorza, Christoph Naber, Andreas Skyschally, Petra Gres, Gerd Heusch, Raimund Erbel, Jörg Barkhausen
Journal: JACC. Cardiovascular imaging (2009)
Treatment of Hepatitis C Infection in Injection Drug Users
Authors: Markus Backmund, Kirsten Meyer, Michael Von Zielonka, Dieter Eichenlaub
Journal: Hepatology (2001)

Chronic hepatitis C is the most common infectious disease among injection drug users (IDUs). Because of the allegedly poor compliance of IDUs with treatment requirements and conditions, hepatologists recommend treatment only if former IDUs have spent 6 to 12 months drug free. The aim of this prospective study was to investigate whether opiate-dependent IDUs with chronic hepatitis C virus (HCV) infection can be treated successfully with interferon. Eligibility for the study meant IDUs had to be HCV-RNA positive by polymerase chain reaction. Subsequently 50 inpatients were enrolled during detoxification treatment. HCV treatment was started with interferon alfa-2a (through 1998) or a combined regimen consisting of interferon alfa-2a and ribavirin (begun in 1998). All patients were treated and supervised by specialized physicians in both hepatology and addiction medicine. The end point for this study was defined as a loss of detectable serum HCV RNA at week 24 after treatment. The rate of sustained virologic response was 36%. Sustained response rates were not significantly different for patients who relapsed and returned to treatment (53%), relapsed and did not return to treatment (24%), or did not relapse (40%; P >.05). During the 24 weeks after treatment, we were unable to detect any reinfection, even among patients who injected heroin during this period. This surprising result should be examined in further studies. In conclusion, HCV-infected drug addicts with chronic HCV infection can be treated successfully with interferon alfa-2a and ribavirin if they are closely supervised by physicians specialized in both hepatology and addiction medicine.
Alliance aims to help health workers in poor countries challenge corruption, excessive pricing, and waste of drugs
Authors: Peter Moszynski
Journal: BMJ (2008)

Patients who have confounded doctors with signs and symptoms that elude diagnosis are to be offered the expertise of hundreds of doctors in a unique programme from the US National Institutes of Health."Physicians deal with about 6600 conditions and 6000 of them are quite rare.Even common diseases have many subtypes," the institutes' director Elias A Zerhouni said during a telephone news conference with reporters earlier this week.He said it was not surprising that many can go undiagnosed for years.The programme aims to combine the revolution in tools and information at the molecular level with the expertise of the 1600 doctors at the NIH Clinical Center "to assist patients around the country and their doctors."It will add to the knowledge base by creating a phenotype atlas of disease."We are doing this now because of the advances that have been made over the last five years at the fundamental level.We have many more biologic markers, the significance of which is not always understood." Dr Zerhouni said that for the first time his organisation was going to apply these sophisticated laboratory tests to human diseases on a large scale.Under the current system of research at the NIH Clinical Center, patients with challenging conditions "are triaged to a specific institute or protocol programme, and are assessed by one team," said John I Gallin, director of the centre.Participants in the new programme "will be assessed by a large spectrum of teams."Candidate patients must be referred by a healthcare provider and will have to submit exhaustive medical records that will be reviewed by a multidisciplinary team of 25 senior doctors.Those who are accepted into the programme will travel to the centre for an evaluation, which is likely to take at least a week.Details are available at http://rarediseases.info.nih.gov/
Parameter variability and the interpretation of physiologically based pharmacokinetic modeling results.
Authors: R C Spear, F Y Bois
Journal: Environmental Health Perspectives (1994)

For the past several years we have been working with models of benzene distribution and metabolism, principally in the rat, but more recently in humans. Our biologically related objectives have been primarily to assist our laboratory-based colleagues in their quest for understanding of the mechanisms by which benzene exerts its toxic action. A secondary goal has been to develop or adapt models useful in risk assessment applications. We have also had methodological goals that relate to applications of sensitivity analysis on the one hand, but more fundamentally to the connection between experimental data and model structure and parameterization. This paper presents an overview of our work in these areas.
Legionella bozemanii Pneumonia and Tetracycline
Authors: SERGIO RUIZ-SANTANA
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 December 1986Legionella bozemanii Pneumonia and TetracyclineSERGIO RUIZ-SANTANA, M.D., JOSE M. AGUADO-BOURREY, M.D., JOSE M. NARVAEZ-BERMEJO, M.D., GEMA GONZALEZ-MEDIERO, M.D.SERGIO RUIZ-SANTANA, M.D.Search for more papers by this author, JOSE M. AGUADO-BOURREY, M.D.Search for more papers by this author, JOSE M. NARVAEZ-BERMEJO, M.D.Search for more papers by this author, GEMA GONZALEZ-MEDIERO, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-6-969_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Five cases of nosocomial pneumonia (1) and one of empyema (2) due to Legionella bozemanii in immunosuppressed patients have recently been reported. We report a case of a community-acquired pneumonia due to this organism occurring in an immunocompetent patient. After initial unresponsiveness to erythromycin, this patient had a clinically favorable response to the addition of tetracycline therapy.A 50-year-old fisherman who worked in dirty freshwater pools was hospitalized because of headache, fever, productive cough, and increasing dyspnea of 7 days' duration. On examination he was obtunded and showed severe respiratory distress with cyanosis, rales, and signs of...References1. PARRY M, STAMPLEMAN L, HUTCHINSON J, FOLTA D, STEINBERG M, and KRASNOGOR L. Waterborne Legionella bozemanii and nosocomial pneumonia in immunosuppressed patients. Ann Intern Med. 1985;103:205-10. LinkGoogle Scholar2. BRETTMAN L, DEHERTOGH D, RANK E, and MANDOUR M. Legionella bozemanii and empyema [Letter]. Ann Intern Med. 1986;105:146-7. LinkGoogle Scholar3. OTERO M, ANDA P, FERNANDEZ M, CASAL J, and NAJERA R. Enfermedad de los legionarios en Espana [Letter]. Lancet (Spanish ed.). 1983;3:149. Google Scholar4. PARKER M, MACHER A, SHELHAMER J, BALOW J, GILL V, and PARRILLO J. Unresponsiveness of Legionella bozemanii pneumonia to erythromycin administration despite in vitro sensitivity. Am Rev Respir Dis. 1983;128:955-6. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SERGIO RUIZ-SANTANA, M.D.; JOSE M. AGUADO-BOURREY, M.D.; JOSE M. NARVAEZ-BERMEJO, M.D.; GEMA GONZALEZ-MEDIERO, M.D.Affiliations: Hospital de Mérida 06800 Mérida, Badajoz Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySevere Legionellosis 1 December 1986Volume 105, Issue 6Page: 969-970KeywordsDyspneaErythromycinFeversHeadachesLegionellaPneumoniaTetracyclines ePublished: 1 December 2008 Issue Published: 1 December 1986 PDF downloadLoading ...
Complementary Populations of Human Adipose CD34+ Progenitor Cells Promote Growth, Angiogenesis, and Metastasis of Breast Cancer
Authors: Stefania Orecchioni, Giuliana Gregato, Ines Martin-Padura, Francesca Reggiani, Paola Braidotti, Patrizia Mancuso, Angelica Calleri, Jessica Quarna, Paola Marighetti, Chiara Aldeni, Giancarlo Pruneri, Stefano Martella, Andrea Manconi, Jean-Yves Petit, Mario Rietjens, Francesco Bertolini
Journal: Cancer Research (2013)

Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.
Excellent therapeutic results achieved in chronic myeloid leukemia patients with front‐line imatinib and early treatment modifications in suboptimal responders: A retrospective study on 91 unselected patients
Authors: Marco Cerrano, Elena Crisà, Patrizia Pregno, Chiara Aguzzi, Paola Riccomagno, Mario Boccadoro, Dario Ferrero
Journal: American Journal of Hematology (2013)

Second generation tyrosine kinase-inhibitors (TKI) have been claimed to represent now the first-choice therapy for chronic myeloid leukemia (CML). Indeed, they generally induce faster and deeper molecular responses compared to imatinib that, however, is equally effective in at least 50% of patients. Moreover, some recent reports have questioned the long term safety of dasatinib and nilotinib. Therefore, upfront imatinib with early shift to second generation TKI for patients with slow/incomplete response might be as effective as front-line second generation TKI, with a possibly better safety profile. We retrospectively evaluated 91 chronic phase CML patients (median follow-up 57 months, median age 61 years), treated front-line with standard-dose imatinib and early therapy modifications (at 3-12 months) in case of unsatisfactory response or intolerance. Thirty-three patients (24 with unsatisfactory response, 9 intolerant) changed therapy, either by increasing imatinib dose (11/91) or by switching to second generation TKI (22 directly, 4 after high-dose imatinib). Globally, our strategy led to complete cytogenetic response (CCyR) in 98% of the patients, major molecular response (MMR) in 88% and molecular response 4 logs (MR(4.0) ) in 62%. Three patients in CCyR (3%), 2 of them in MMR too, suddenly progressed to blastic phase. At the last follow-up nine patients had died, seven of CML-unrelated causes and two only of CML progression. These results suggest that our strategy could be as effective as front line second generation TKI, with most of patients still receiving imatinib, a drug of better known long-term side effects and lower cost.
Some Things Have Not Changed
Authors: Linda Hawes Clever
Journal: Annals of Internal Medicine (2000)

The profession of medicine faces unprecedented pressures that jeopardize physicians' ability to care for patients. This is the perfect time for physicians to look back at the history of medicine; examine our own personal journeys; and reflect on our ideals, commitments, and accomplishments. To be effective leaders for medicine and health, physicians must work together. We must be vigilant about threats to high standards, research, education, and ethics and seize opportunities for improvement. We need to ensure that relationships with patients, students and housestaff, and other colleagues are marked by trust and healing. The days, years, and careers that we spend caring for others are most sustainable and satisfying if we also care for ourselves and our families. Many elements are required for physicians to maintain the lifegiving capabilities of our profession. Principles and thought combined with action have carried and buoyed medicine throughout time. This must not change.
Delay in diagnosis of homocystinuria: retrospective study of consecutive patients
Authors: J. R M Cruysberg, G. H J Boers, J M F. Trijbels, A. F Deutman
Journal: BMJ (1996)

To assess the causes for delay in the diagnosis of homocystinuria.Clinical and laboratory data were collected from patients diagnosed as having homocystinuria due to cystathionine synthase deficiency, with special reference to the ages at which the patients had their first major signs of the disease, ectopia lentis was established, and homocystinuria was diagnosed.University hospital in the Netherlands.34 patients (18 males) in whom homocystinuria due to cystathionine synthase deficiency was diagnosed in the period 1970-94.Among 34 consecutively detected homocystinuria patients the mean age at diagnosis of homocystinuria was 24 (range 1-61) years. Despite frequent ocular manifestations, serious complications in the vascular, skeletal, and central nervous systems, and repeated examinations performed in these patients by clinicians of various disciplines, there was a mean delay of 11 (0-43) years between the first major signs of the disease (at mean age 13 (1-40) years) and the ultimate diagnosis of homocystinuria. Even when ectopia lentis was diagnosed (in 26 (76%) patients, mean age 18 (1-50) years), this did not lead to adequate biochemical analysis for homocystinuria at the time of detection, causing a mean diagnostic delay of 8 (0-24) years in these patients.Three factors should have precipitated the diagnosis of homocystinuria: early recognition that unusual myopia (high, very high, abnormal progressive, or at young age) was caused by subluxation of the ocular lenses; awareness that the occurrence of myopia combined with systemic complications ("myopia plus") might be due to homocystinuria; and appropriate biochemical investigations carried out in patients with ectopia lentis and in their siblings.