tbuckley/cabot-search huggingface dataset:
Chronic Rhinosinusitis: The Unrecognized Epidemic
Authors: Bruce K. Tan, Robert C. Kern, Robert P. Schleimer, Brian S. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rhinosinusitis is defined on the basis of the four cardinal symptoms of obstruction, drainage, smell loss, and facial pain or pressure in both acute (ARS) and chronic (CRS) rhinosinusitis, with CRS distinguished by a duration of symptoms of 3 or more months. The determinants of progression from ARS to CRS remain underexplored, but CRS differs from ARS in microbiology, with the most commonly cultured ARS pathogens rarely found in CRS. For the diagnosis of CRS, guidelines further recommend that symptoms be accompanied by objective evidence of sinus inflammation on the basis of sinus computed tomography (CT) scan or nasal endoscopy (1–3). These recommendations were necessary because it remains difficult to accurately differentiate whether a patient presenting with a chief complaint of 4 months of symptoms of facial pain or pressure, bilateral nasal obstruction, and nasal discharge has recurrent ARS, CRS, allergic rhinitis, or migraine without results from diagnostic tests such as nasal endoscopy, a CT scan, or atopy testing. Using symptoms alone, it is also difficult to differentiate important clinical subtypes of CRS such as CRS with nasal polyps (CRSwNP). Indeed, studies from tertiary care institutions report that only about half the patients with characteristic CRS symptoms have objective evidence of sinus inflammation (4, 5). Because diagnosis at the point of encounter has significant impact on treatment, the assumption of a CRS diagnosis on the basis of characteristic symptoms alone likely leads to excessive diagnosis and treatment.
Bacterial Variations in the Nasopharynx and Skin of Isolated Arctic Scientists
Authors: Robert W. Christie
Journal: New England Journal of Medicine (1958)

THERE have been several studies on the interrelation of nose and skin bacteria in unisolated groups of human beings,1 2 3 but little has been written about variations in the micro-organisms of the nose and skin of closely confined groups of human beings over a period of several months.It was possible to evaluate the qualitative variations of aerobic bacterial populations of the nasopharynx and skin of 7 male members of a scientific exploratory expedition living closely together and completely isolated for a hundred days on the Greenland Ice Cap.4 The environmental conditions were favorable to such a study, since low temperatures . . .
Chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1l) gene suppresses the nucleus-to-mitochondria translocation of nur77 to sustain hepatocellular carcinoma cell survival
Authors: Leilei Chen, Liang Hu, Tim Hon Man Chan, George Sai-Wah Tsao, Dan Xie, Ke-Ke Huo, Li Fu, Stephanie Ma, Bo-Jian Zheng, Xin-Yuan Guan
Journal: Hepatology (2009)

Abstract Amplification of 1q21 has been detected in 58% to 78% of primary hepatocellular carcinoma cases, suggesting that one or more oncogenes within the amplicon play a critical role in the development of this disease. The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene ( CHD1L ) is a recently identified oncogene localized at 1q21. Our previous studies have demonstrated that CHD1L has strong tumorigenic ability and confers high susceptibility to spontaneous tumors in a CHD1L -transgenic mouse model. In this study, we demonstrate that the antiapoptotic ability of CHD1L is associated with its interaction with Nur77, a critical member of a p53-independent apoptotic pathway. As the first cellular protein identified to bind Nur77, CHD1L is able to inhibit the nucleus-to-mitochondria translocation of Nur77, which is the key step of Nur77-mediated apoptosis, resulting in the hindrance of the release of cytochrome c and the initiation of apoptosis. Knock-down of CHD1L expression by RNA interference could rescue the mitochondrial targeting of Nur77 and the subsequent apoptosis. Further studies found that the C-terminal Macro domain of CHD1L is responsible for the interaction with Nur77, and a CHD1L mutant lacking residues 600-897 failed to interact with Nur77 and prevented Nur77-mediated apoptosis. More importantly, we found that the inhibition of Nur77-mediated apoptosis by endogenous CHD1L is a critical biological cellular process in hepatocarcinogenesis. Conclusion: We demonstrate in this study that overexpression of CHD1L could sustain tumor cell survival by preventing Nur77-mediated apoptosis. (Hepatology 2009.)
COMPARISON OF BLEEDING DEFINITIONS, BARC, GUSTO, TIMI AND VARC IN PATIENTS UNDERGOING BALLOON AORTIC VALVULOPLASTY: RESULTS FROM A TWO-CENTER REGISTRY
Authors: Jennifer Yu, Usman Baber, Annapoorna Kini, Georgios Vlachojannis, Samantha Sartori, Brian O&apos;Neill, David Knopf, Shyam Poludasu, Pedro Martinez&ndash;Clark, Jason Kovacic, Robert Pyo, Pedro Moreno, William O&apos;Neill, Mauricio Cohen, Roxana Mehran, Samin Sharma, George Dangas
Journal: Journal of the American College of Cardiology (2012)
Vaccination Against Pneumococcal Infection
Authors: PAUL DRINKA
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 May 1986Vaccination Against Pneumococcal InfectionPAUL DRINKA, M.D., MAVIS SIEWERT, R.N.PAUL DRINKA, M.D.Search for more papers by this author, MAVIS SIEWERT, R.N.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-5-722 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the article on cost effectiveness of vaccination against pneumococcal pneumonia, Sisk and Riegelman (1) estimate that, at most, 20% to 35% of the recommended target group has been immunized. We write to share our successful approach to the administration of the pneumococcal vaccine in a nursing home. Our patient population invariably falls into the group of persons with chronic conditions that increase the risk of pneumococcal disease or who are age 65 and older. Our organization's approach has resulted in vaccination in a high percentage of patients for the last 5 years.The Wisconsin Veterans Home...Reference1. SISK J and RIEGELMAN R. Cost effectiveness of vaccination against pneumococcal pneumonia: an update. Ann Intern Med. 1986;104:79-86. LinkGoogle Scholar1. BOLAN G, BROOME C, FACKLAM R, PLIKAYTIS B, FRASER D, and SCHLECH W. Pneumococcal vaccine efficacy in selected populations in the United States. Ann Intern Med. 1986;104:1-6. LinkGoogle Scholar2. SISK J and RIEGELMAN R. Cost effectiveness of vaccination against pneumococcal pneumonia: an update. Ann Intern Med. 1986;104:79-86. LinkGoogle Scholar3. WILLIAMS J and MOSER K. Pneumococcal vaccine and patients with chronic lung disease. Ann Intern Med. 1986;104:106-9. LinkGoogle Scholar4. LAFORCE F and EICKHOFF T. Pneumococcal vaccine: the evidence mounts [Editorial]. Ann Intern Med. 1986;104:110-1. LinkGoogle Scholar5. . Pneumococcal vaccine. Ann Intern Med. 1986;104:118-20. LinkGoogle Scholar1. Guide for Adult Immunization, 1985. Philadelphia: American College of Physicians; 1985. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: PAUL DRINKA, M.D.; MAVIS SIEWERT, R.N.Affiliations: Wisconsin Veterans Home King, WI 54946 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBibliographyInfluenza and Pneumococcal Immunization Strategies for Physicians 1 May 1986Volume 104, Issue 5Page: 722-723KeywordsFallsNursing homesPneumoniaVaccines ePublished: 1 December 2008 Issue Published: 1 May 1986 PDF downloadLoading ...
NEW ASPECTS OF YELLOW FEVER ETIOLOGYARISING FROM THE EXPERIMENTAL FINDINGS OF THE LAST THREE YEARS.
Authors: CARLOS J. FINLAY
Journal: JAMA (1904)

In the light of modern researches yellow fever must now be considered as a disease produced, in individuals belonging to certain human races, by a two-host, microscopic, perhaps ultra-microscopic germ, endoparasite of the female of a particular species of mosquito—the<i>Stegomyia fasciata</i>(Theobald). This germ pursues its parasitic existence in the body of the infected stegomyia during a period of 59 days, as experiments have proved, and probably, under ordinary circumstances, till the death of its mosquito-host. In order, however, that it may complete its life cycle, secure the perpetuation of its species and find its way into the body of other healthy stegomyias, it is necessary that it should penetrate, through the bite of the infected insect, into the body of a person who is liable to undergo an attack of yellow fever. After parting from its mosquito-host, the germ apparently goes through certain evolutions in the body of
Points: High-pressure water jet injury
Authors: J. King
Journal: BMJ (1980)

<h3>Background:</h3> Health Links are a new model of providing care coordination for high-cost, high-needs patients in Ontario. We evaluated use of hospital-related health care services among Health Links patients in the Central Local Health Integration Network (LHIN) of Ontario in the year before versus after program enrolment and compared rates of use with those among similar patients with complex needs not enrolled in the program (comparator group). <h3>Methods:</h3> We identified all patients who received a Health Links coordinated care plan before Jan. 1, 2015, using linked registry and health administrative data. We used propensity scores to match (1:1) enrollees (registry) with comparator patients (administrative data). Using a difference-in-differences approach with generalized estimating equations, we evaluated 5 measures of Health Link performance: rates of hospital admission, emergency department visits, days in acute care, 30-day readmissions and 7-day postdischarge primary care follow-up. <h3>Results:</h3> Of the 344 enrollees in the registry, we matched 313 [91.0%] to comparator patients. All measured sociodemographic, comorbidity and health care use characteristics were balanced between the 2 groups (all standardized differences &lt; 0.10). For enrollees, the rate of days in acute care per person-year increased by 35% (incidence rate ratio 1.35 [confidence interval 1.11-1.65]) after versus before the index date, but differences were nonsignificant for all other measures. Difference-in-differences analyses revealed greater reductions in hospital admissions, emergency department visits and acute care days after the index date in the comparator group than among enrollees. <h3>Interpretation:</h3> Initial implementation of the Health Link program in the Central LHIN did not reduce selected indicators of Health Link performance among enrollees. As the Health Link program evolves and standardization is implemented, future research may reveal effects from the initiative in other outcomes or with longer follow-up.
Robust Suppression of HIV Replication by Intracellularly Expressed Reverse Transcriptase Aptamers Is Independent of Ribozyme Processing
Authors: Margaret J Lange, Tarun K Sharma, Angela S Whatley, Linda A Landon, Michael A Tempesta, Marc C Johnson, Donald H Burke
Journal: Molecular Therapy (2012)

RNA aptamers that bind human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) also inhibit viral replication, making them attractive as therapeutic candidates and potential tools for dissecting viral pathogenesis. However, it is not well understood how aptamer-expression context and cellular RNA pathways govern aptamer accumulation and net antiviral bioactivity. Using a previously-described expression cassette in which aptamers were flanked by two "minimal core" hammerhead ribozymes, we observed only weak suppression of pseudotyped HIV. To evaluate the importance of the minimal ribozymes, we replaced them with extended, tertiary-stabilized hammerhead ribozymes with enhanced self-cleavage activity, in addition to noncleaving ribozymes with active site mutations. Both the active and inactive versions of the extended hammerhead ribozymes increased inhibition of pseudotyped virus, indicating that processing is not necessary for bioactivity. Clonal stable cell lines expressing aptamers from these modified constructs strongly suppressed infectious virus, and were more effective than minimal ribozymes at high viral multiplicity of infection (MOI). Tertiary stabilization greatly increased aptamer accumulation in viral and subcellular compartments, again regardless of self-cleavage capability. We therefore propose that the increased accumulation is responsible for increased suppression, that the bioactive form of the aptamer is one of the uncleaved or partially cleaved transcripts, and that tertiary stabilization increases transcript stability by reducing exonuclease degradation.
RhoA protects the mouse heart against ischemia/reperfusion injury
Authors: Sunny Yang Xiang, Davy Vanhoutte, Dominic P. Del Re, Nicole H. Purcell, Haiyun Ling, Indroneal Banerjee, Julie Bossuyt, Richard A. Lang, Yi Zheng, Scot J. Matkovich, Shigeki Miyamoto, Jeffery D. Molkentin, Gerald W. Dorn, Joan Heller Brown
Journal: Journal of Clinical Investigation (2011)

The small GTPase RhoA serves as a nodal point for signaling through hormones and mechanical stretch. However, the role of RhoA signaling in cardiac pathophysiology is poorly understood. To address this issue, we generated mice with cardiomyocyte-specific conditional expression of low levels of activated RhoA (CA-RhoA mice) and demonstrated that they exhibited no overt cardiomyopathy. When challenged by in vivo or ex vivo ischemia/reperfusion (I/R), however, the CA-RhoA mice exhibited strikingly increased tolerance to injury, which was manifest as reduced myocardial lactate dehydrogenase (LDH) release and infarct size and improved contractile function. PKD was robustly activated in CA-RhoA hearts. The cardioprotection afforded by RhoA was reversed by PKD inhibition. The hypothesis that activated RhoA and PKD serve protective physiological functions during I/R was supported by several lines of evidence. In WT mice, both RhoA and PKD were rapidly activated during I/R, and blocking PKD augmented I/R injury. In addition, cardiac-specific RhoA-knockout mice showed reduced PKD activation after I/R and strikingly decreased tolerance to I/R injury, as shown by increased infarct size and LDH release. Collectively, our findings provide strong support for the concept that RhoA signaling in adult cardiomyocytes promotes survival. They also reveal unexpected roles for PKD as a downstream mediator of RhoA and in cardioprotection against I/R.
Activity of endogenous myocardial lipases during incubation at acid pH
Authors: W. B. WEGLICKI, K. OWENS, R. C. RUTH, E. H. SONNENBLICK
Journal: Cardiovascular Research (1974)

Journal Article Activity of endogenous myocardial lipases during incubation at acid pH Get access WILLIAM B. WEGLICKI, WILLIAM B. WEGLICKI 2 From the Cardiovascular Division, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School Boston, Massachusetts, USA 2Address for correspondence: William B. Weglicki, MD, Cardiovascular Division, Department of Medicine, Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Massachusetts 02115, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar KENNETH OWENS, KENNETH OWENS From the Cardiovascular Division, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School Boston, Massachusetts, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar ROBIN C. RUTH, ROBIN C. RUTH From the Cardiovascular Division, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School Boston, Massachusetts, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar EDMUND H. SONNENBLICK EDMUND H. SONNENBLICK From the Cardiovascular Division, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School Boston, Massachusetts, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 2, March 1974, Pages 237–242, https://doi.org/10.1093/cvr/8.2.237 Published: 01 March 1974
Edwin Dennis Kilbourne
Authors: N. Stafford
Journal: BMJ (2011)

Discovered way to mass produce influenza vaccines



AP/PA

It was 42 years ago, in 1969, when Edwin D Kilbourne wrote a paper that would lay the groundwork for a new weapon to fight the ever evolving flu virus ( Bulletin of the World Health Organization 1969;41:643-5). In the paper, Kilbourne describes a process for producing genetically engineered influenza vaccines by recombining new virus strains with a fast growing, standard laboratory strain. His method became the standard for producing large quantities of flu vaccines each year for mass immunisation.

“It is a classic paper,” said Doris Bucher, who in 1969 joined Kilbourne’s team at Mount Sinai School of Medicine in New York City and now is associate professor of microbiology and immunology at New York Medical College. “At the time it wasn’t known that the flu genome is segmented and reassorts segments rather than recombining.” She added that the process “has, at a minimum, permitted double the production of vaccine doses annually than would be possible with the wild-type isolates.”

Just a few years after publication of the paper, Kilbourne would have the opportunity to use the process on a huge scale, an experience that years later …
A proposal for grading nasomucosal injury as a complication of transnasal endoscopy
Authors: A. Mori, N. Ohashi, T. Maruyama, M. Ito, T. Miyawaki, M. Okuno
Journal: Endoscopy (2008)

Unsedated transnasal esophagogastroduodenoscopy (EGD) using an ultrathin scope has been developed as an alternative method to conventional endoscopy with sedation [1] [2]. Several studies have reported the benefit of transnasal EGD, which may reduce the risk of cardiopulmonary complications, lower the cost related to postprocedure monitoring, and be better tolerated by the patients [1] [2] [3]. However, lack of data regarding the safety of the procedure hinders widespread usage of unsedated nasal endoscopy [4]. In fact, according to the Technology Status Evaluation Report of the American Society for Gastrointestinal Endoscopy, the complication rate associated with nasal EGD remains unknown [5]. Thus, it may be useful to determine criteria for estimating the complications related to nasal EGD, including epistaxis, which occurs in a few percent of patients. We propose a grading system for nasomucosal injury caused by the transnasal insertion of an endoscope.
Gonococcal interactions with polymorphonuclear neutrophils: importance of the phagosome for bactericidal activity.
Authors: P Densen, G L Mandell
Journal: Journal of Clinical Investigation (1978)

Gonococci are capable of attaching to the surface of polymorphonuclear leukocytes (PMN). In this location they resist phagocytosis and are not killed by PMN. To delineate the factors involved in the survival of these gonococci, we investigated the interaction of virulent gonococci, which adhere to cells and resist phagocytosis, and avirulent gonococci, which are phagocytized and killed by PMN. In the presence of serum, both virulent and avirulent gonococci associate equally well with PMN and stimulate increases in oxidative metabolism. In the absence of serum virulent gonococci attached to PMN and stimulated PMN oxidative metabolism to a greater extent than avirulent gonococci which did not attach to PMN (P = 0.0009). Therefore, the survival of virulent gonococci attached to the PMN surface is not a result of failure to activate oxidative and bactericidal mechanisms. Both virulent and avirulent gonococci stimulated equivalent PMN specific granule release as measured by the appearance of lactoferrin in the media. Phagocytosis of avirulent gonococci stimulated significantly greater beta-glucuronidase release (P = 0.01) and myeloperoxidase-mediated iodination of protein (P = 0.001) by PMN than attachment of virulent gonococci. In the absence of serum neither type of gonococci stimulated beta-glocuronidase release or protein iodination by PMN. Thus, virulent gonococci fail to stimulate primary granule release by PMN. To further assess the role of attachment versus ingestion on the survival of gonococci, PMN were treated with cytochalasin B to block ingestion. Cytochalasin B-treated PMN were unable to kill either virulent or avirulent gonococci despite normal degranulation stimulated by the latter. The failure of PMN to kill surface-attached gonococci appears to be a consequence of the failure of PMN to enclose the virulent gonococci within a phagosome. The phagocytic vacuole thus plays a critical role in normal PMN bactericidal activity by providing a closed space in which the proper concentration of substances may be achieved to generate microbicidal activity.
In vivo aortic muscle cell growth kinetics. Differences between thoracic and abdominal segments after intimal injury in the rabbit.
Authors: I D Goldberg, M B Stemerman, B J Ransil, R L Fuhro
Journal: Circulation Research (1980)

Focal proliferation of smooth muscle cell (SMC) is an integral part of atherosclerotic plaque formation: characterization of regional variation in SMC growth kinetics is therefore important to the understanding of atherogenesis. SMC growth kinetics of rabbit abdominal and thoracic segments were compared. Rabbit aortas were denuded of endothelium and the animals killed after 3H-thymidine and Evans blue injections at 0 to 48 days after denudation. Incorporation of 3H-thymidine into both aortic segments peaked at 48 hours; no detectable incorporation occurred in the first 24 hours. Abdominal segment DNA specific activity (SA, dpm/micrograms DNA) and total kinetic activity (TKA, dpm/0.1 mm internal elastic lamina) at 48 hours were significantly greater than values for the thoracic aorta. Abdominal SA and TKA curves decreased exponentially after the 48-hour peak and parallel thoracic levels after day 7. SA and TKA values for each segment reflected the subsequent SMC intimal growth rates as measured morphometrically. Therefore, both segments share similar growth kinetic characteristics; however, the abdominal response to initimal injury is greater than the thoracic and leads to greater myointimal proliferation. The difference in response to injury in the two segments suggests regional variation in SMC's which are phenotypically similar.