tbuckley/cabot-search huggingface dataset:
Improvement of cardiac function with device‐based diaphragmatic stimulation in chronic heart failure patients: the randomized, open‐label, crossover <scp>E</scp>piphrenic <scp>II P</scp>ilot <scp>T</scp>rial
Authors: Remo Beeler, Andreas W. Schoenenberger, Peter Bauer, Richard Kobza, Michael Bergner, Xavier Mueller, Reinhard Schlaepfer, Michel Zuber, Susanne Erne, Paul Erne
Journal: European Journal of Heart Failure (2013)
Understanding of the pathophysiology of pemphigus suggests innovative therapeutic approaches
Authors: J.R. Stanley
Journal: British Journal of Dermatology (2000)

It may take decades, or even centuries, but eventually the careful study of the pathophysiology of disease will allow the design of rational therapy. We are now at that critical juncture in our understanding of pemphigus. The biomedical journey started with the first clinical and histological descriptions of pemphigus, which allowed us to differentiate the major types, pemphigus vulgaris and pemphigus foliaceus. 1, 2 The next major milestone was the finding of immunoglobulin in the skin and sera of pemphigus patients. 3 These findings suggested that pemphigus was an autoimmune disease, a hypothesis that was confirmed experimentally in organ culture and mouse models of disease. 4, 5 This understanding led to our current therapy of pemphigus, which is based on immunosuppression. The identification of autoantibodies then led to their use to identify the antigens involved. 6 Further characterization and molecular cloning indicated that pemphigus antigens were desmosomal cadherins, namely desmoglein 1 (pemphigus foliaceus) and desmoglein 3 (pemphigus vulgaris). 7–9 These discoveries suggested that pemphigus autoantibodies might interfere with the adhesive function of desmogleins in the desmosome. This hypothesis was supported by the recent finding that a mouse with a targeted deletion of the desmoglein 3 gene has a phenotype similar to pemphigus vulgaris patients, including oral mucosal and skin erosions that show the typical histology of the disease. 10
498. AAV Δ264CFTR Enhances Maturation of ΔF508CFTR and wt CFTR Expression
Authors: Liudmila Cebotaru, Terence R. Flotte, William B. Guggino
Journal: Molecular Therapy (2006)

We have presented previously that high dose airway delivery of a pseudotyped AAV2/5 vector to the lungs of Rhesus macaques resulted in enhanced gene transfer and quantitative RNA expression as well as protein expression in non human primates without clinical toxicity. One major limitation to the success of AAV gene therapy for CF is that the large size of the CFTR cDNA insert fills the packaging capacity of AAV viral particles precluding inclusion of a highly efficient promoter. In order to overcome this limitation AAV2/5 pseudotyped vectors were generated expressing a truncated CFTR insert (Δ264) driven by a chicken beta actin promoter (rAAV-CB- Δ264-CFTR). We showed previously that this truncated form was capable of reconstituting physiologic function in vitro and in mouse models. Aims: To assess the effect of rAAV-CB-Δ264CFTR vector on ΔF508 and wt CFTR protein expression. The ΔF508 form of CFTR is the most common mutant form in patients with CF. Methods: Either ΔF508 CFTR or wt CFTR plasmids were transfected individually or cotransfected in combination with the rAAV-CB-264CFTR plasmid into Cos7 cells. After 48 hours cells were harvested and protein was used for western blot assays. Results: Both ΔF508 CFTR and Δ264CFTR could be detected in transfected and cotransfected cells. Mature C band from ΔF508 CFTR was significantly increased by 55% in cells cotransfected with ΔF508 CFTR and rAAV-CB-Δ264CFTR versus cells expressing ΔF508 alone. Both wt CFTR and Δ264CFTR could also be detected in transfected and cotransfected cells. Wt CFTR band C was also significantly increased by 43% in cells cotransfected with wt CFTR and rAAV-CB-Δ264CFTR versus cells expressing wt CFTR alone. An increased expression of endogenous wt CFTR was also observed previously when monkeys were infected with rAAV-CB- Δ264CFTR. Conclusion: rAAV-CB-Δ264CFTR vector enhanced maturation of mature ΔF508 C band and increased expression of mature wt CFTR. Several studies have reported transcomplementation of ΔF508 CFTR in cells transfected with only parts of CFTR (Cormet-Boyaka, PNAS 101-8221-6, 2004). These fragments improved the maturation of ΔF508 CFTR. Our data suggest that truncated forms of CFTR may be useful gene therapy vectors by affecting the maturation of endogenous CFTR.
Abstract 16289: Can We Personalize CPR? Challenges With Hemodynamics, Monitoring, and Pharmacology
Authors: Joshua W Lampe, Tai Yin, George Bratinov, Theodore Weiland, Christopher L Kaufman, Lance B Becker
Journal: Circulation (2014)

Introduction: Coronary perfusion pressure (CPP) guided CPR improves survival over guideline CPR. EtCO2 has also been used to guide CPR. These efforts reflect that one-size-fits-all CPR is sub-optimal, but assume that CPP and EtCO2 guidance will result in similar definitions of “high quality” chest compressions (CC). A mechanistic study of the interaction between CC, blood flow, CPP, and EtCO2 has not been done. Methods: CPR was performed on 21 domestic swine (~30 Kg) using standard physiological monitoring. Flow was measured in the abdominal aorta, the inferior vena cava (IVC), the right renal artery and vein, the right common carotid and external jugular. Ventricular fibrillation (VF) was electrically induced. Mechanical CC were started after ten minutes of VF. CC waveforms varied so that sternal release occurred over 100 ms, 200 ms, or 300 ms. CC were delivered at a rate of 100 per minute and at a depth of 1.25” (n=9), 1.9” (n=8), or 1.9” with vasopressor use (n=4) for a total of 54 min. CC release times changed every 2 min and were randomized. Results: In the first 18 min of CPR, EtCO2 was optimized by a 100 ms release (27.2±2.5 mmHg) vs. a 200 ms (24.7±2.5 mmHg; p = .005) or 300 ms release (25.1±2.5 mmHg; p= 0.03). CPP was optimized by a 200 ms release (6.7±1.0 mmHg) vs. a 100 ms (5.7±1.0 mmHg; p = 0.03) or 300 ms (4.9±1.0 mmHg; p &lt; 0.01) release. Deeper CC increased blood flow in the IVC (1.5±0.2 vs. 0.12±0.2 mL/comp: p&lt;0.001) and carotid artery (0.4±0.03 vs. 0.2±0.03 mL/comp: p&lt;0.001) and changed the distribution of blood flow. In prolonged CPR, CC efficacy decayed with time, particularly with 1.25” CC, and resulted in distinct periods of to and fro flow (sloshing). Vasopressor effects appeared to be time dependent, but trended towards improved CPP at the expense of significantly reduced carotid blood flow. Conclusions: CPP and EtCO2 provide insight into two distinct aspects of CC generated blood flow, and consequently cannot be simultaneously optimized. CC generated blood flow transitions from forward blood flow to sloshing as a function of time and CC depth. Pressure measurements are insufficient to titrate vasopressor use, as tissue perfusion can collapse while maintaining the CPP. We currently lack the monitoring and the physiological understanding required to personalize CPR.
Factors Determining Homograft Destruction and Immunological Enhancement in Mice Receiving Successive Tumor Inocula&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Nathan Kaliss, Bradley F. Bryant
Journal: JNCI Journal of the National Cancer Institute (1958)

Journal Article Factors Determining Homograft Destruction and Immunological Enhancement in Mice Receiving Successive Tumor Inocula Get access Nathan Kaliss, Nathan Kaliss Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Bradley F. Bryant Bradley F. Bryant Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 4, April 1958, Pages 691–704, https://doi.org/10.1093/jnci/20.4.691 Published: 01 April 1958 Article history Received: 13 September 1957 Published: 01 April 1958
Safer non-cardiac surgery for patients with coronary artery disease
Authors: J. Sonksen, R. Gray, P. H. Hickman
Journal: BMJ (1998)

How best to manage patients with coronary artery disease who undergo major non-cardiac surgery is an increasingly important issue as the populationages. Such patients, particularly those with easily induced ischaemia, are at increased risk of perioperative cardiac complications and death.1 Various pre-emptive interventions have beenconsidered to minimise this risk, but often their precise role is poorly defined.

Coronary artery bypass grafting is effective but carries its own risks, and overall survival benefit is seen only in patients who warrant bypass surgery independently of their major non-cardiac operation.2 These patients, although few, are a well defined3 population who should be offered prophylactic coronary revascularisation. The role of percutaneous transluminal coronary angioplasty is less well defined because, even in the wider populationof patients with coronary artery disease, no prospective randomised trial has shown a prognostic benefit for angioplasty over medical treatment. Use of preoperative angioplasty should therefore be restricted to patients with readily inducible ischaemia, in whom a single coronary stenosis subtends a large area of viable myocardium.4

Most patients with coronary artery disease presenting for elective …
Influenza Vaccination Coverage Among Health Care Personnel — United States, 2015–16 Influenza Season
Authors: Carla L. Black, Xin Yue, Sarah W. Ball, Sara M.A. Donahue, David Izrael, Marie A. de Perio, A. Scott Laney, Walter W. Williams, Megan C. Lindley, Samuel B. Graitcer, Peng-Jun Lu, Charles DiSogra, Rebecca Devlin, Deborah K. Walker, Stacie M. Greby
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all health care personnel to reduce influenza-related morbidity and mortality among both health care personnel and their patients (1-4). To estimate influenza vaccination coverage among U.S. health care personnel for the 2015-16 influenza season, CDC conducted an opt-in Internet panel survey of 2,258 health care personnel during March 28-April 14, 2016. Overall, 79.0% of survey participants reported receiving an influenza vaccination during the 2015-16 season, similar to the 77.3% coverage reported for the 2014-15 season (5). Coverage in long-term care settings increased by 5.3 percentage points compared with the previous season. Vaccination coverage continued to be higher among health care personnel working in hospitals (91.2%) and lower among health care personnel working in ambulatory (79.8%) and long-term care settings (69.2%). Coverage continued to be highest among physicians (95.6%) and lowest among assistants and aides (64.1%), and highest overall among health care personnel who were required by their employer to be vaccinated (96.5%). Among health care personnel working in settings where vaccination was neither required, promoted, nor offered onsite, vaccination coverage continued to be low (44.9%). An increased percentage of health care personnel reporting a vaccination requirement or onsite vaccination availability compared with earlier influenza seasons might have contributed to the overall increase in vaccination coverage during the past 6 influenza seasons.
Structure-Activity Relationships in the Development of Allosteric Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibitors: Ten Years of Research
Authors: Romain Haudecoeur, Marine Peuchmaur, Abdelhakim Ahmed-Belkacem, Jean-Michel Pawlotsky, Ahcène Boumendjel
Journal: Medicinal Research Reviews (2012)

Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) possesses a single positive strand RNA genome encoding a polyprotein composed of approximatively 3000 amino acids. The polyprotein is cleaved at multiple sites by cellular and viral proteases to liberate structural and nonstructural (NS) proteins. NS5B, the RNA-dependent RNA polymerase (RdRp), which catalyzes the HCV RNA replication has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-acting antivirals). In the last 10 years, a growing number of non-nucleoside compounds have been reported as RdRp inhibitors and few are undergoing clinical trials. Over the past 5 years, several reviews were published all describing potentially active molecules. To the best of our knowledge, only one review covers the structure–activity relationships.1 In this review, we will discuss the reported non-nucleoside molecules acting as RdRp inhibitors according to their chemical class especially focusing on structure–activity relationship aspects among each class of compounds. Thereafter, we will attempt to address the global structural requirements needed for the design of specific inhibitors of RdRp.
Clusters of Brazilian spotted fever in São Paulo State, southeastern Brazil. A review of official reports and the scientific literature
Authors: R. Nogueira Angerami, E.M. Nunes, E.M. Mendes Nascimento, A. Ribas Freitas, B. Kemp, A.F.C. Feltrin, M.R. Pacola, G.E.C. Perecin, V. Sinkoc, M. Ribeiro Resende, G. Katz, L. Jacintho da Silva
Journal: Clinical Microbiology and Infection (2009)
Role of p53 positivity on the survival of patients with lung cancer as assessed by a systematic review of the literature.
Authors: Emmanuelle Steels, Marianne Paesmans, Thierry Berghmans, Fabrice Branle, Agnès Burniat, Lidia Ghisdal, Jean-Jacques Lafitte, Céline Mascaux, Anne-Pascale Meert, Frédéric Vallot, Jean-Paul Sculier
Journal: European Respiratory Journal (2000)
Abstract 568: Few Carney's Triad patients have mutations in two subunits of the succinate dehydrogenase enzyme (SDHB, SDHC)
Authors: Sosipatros A. Boikos, Paraskevi Xekouki, Fabio R. Faucz, Karel Pacak, Margarita Raygada, Karen Adams, Evan Szarek, Evan Ball, Su Young Kim, Elena Fumagalli, Lee J. Helman, J Aidan Carney, Constantine A. Stratakis
Journal: Cancer Research (2014)

Abstract Carney's triad (CTr) is a non-hereditary condition, primarily seen in young women, characterized by gastrointestinal stromal tumors (GIST), extra-adrenal paragangliomas and pulmonary chondromas. Most CTr patients present with GIST and pulmonary chondroma (incomplete CTr). A marked decrease in the enzymatic activity of succinate dehydrogenase (SDH) has been detected in these tumors, but the presence or absence of SDH mutations in CTr is controversial. A related disease, known as Carney-Stratakis Syndrome (CSS), has no female predisposition and presents with extra-adrenal paragangliomas and GIST tumors, without pulmonary chondromas. In distinction to CTr, CSS is hereditary due to germline SDH mutations in the enzyme's subunits (SDHA, SDHB, SDHC and SDHD) with corresponding decreased SDH activity in associated tumors. We have investigated 64 patients with CTr for germline mutations and/or deletions in the SDH subunit genes; four patients were found to have germline mutations in SDHB or SDHC. All four patients had multifocal gastric GIST and pulmonary chondromas at diagnosis; two subsequently developed paragangliomas, confirmed by biopsy. One of the patients with CTr and a SDHB mutation had a nephew with the same mutation and a neuroblastoma, confirming a previously reported association of neuroblastoma with gist (JMG 2009; 46:215, and AJMG 2010; 152A: 1531). We conclude that few CTr patients maybe more correctly classified as having CSS; the genetic distinction of CTr from CSS needs further study. [S.A.B. and P.X. should be regarded as joint first authors.] Citation Format: Sosipatros A. Boikos, Paraskevi Xekouki, Fabio R. Faucz, Karel Pacak, Margarita Raygada, Karen Adams, Evan Szarek, Evan Ball, Su Young Kim, Elena Fumagalli, Lee J. Helman, J Aidan Carney, Constantine A. Stratakis. Few Carney's Triad patients have mutations in two subunits of the succinate dehydrogenase enzyme (SDHB, SDHC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 568. doi:10.1158/1538-7445.AM2014-568
Abstract 17481: MicroRNAs Mediate the Protective Effect of Angiotensin Converting Enzyme Inhibition (ACEi) on the Heart in Rat Model of Acute Kidney Injury
Authors: Indrajeet Rana, Elena Velkoska, Louise M Burrell, Fadi J Charchar
Journal: Circulation (2014)

Introduction: Cardiovascular complications are common in patients with kidney disease. MicroRNAs play an important role in regulating cell death pathways and cardiac hypertrophy but it is not known whether cardiac microRNAs contribute to cardio-renal cross talk. microRNA-1 and microRNA-133 are associated with cardiac fibrosis and apoptosis after myocardial infarction, whilst microRNA-212/132 is associated with cardiac hypertrophy. Aim: Using a rat model we investigated whether acute kidney injury leads to changes in cardiac microRNAs (1,133,212 and 132) and their gene targets. We also tested the effect of treatment with the angiotensin converting enzyme inhibitor (ACEi) ramipril on these cardiac microRNAs. Methods: Heart tissues were collected from rats 10 days after subtotal nephrectomy (STNx) surgery, where one kidney was removed and the other partially ligated (n=9), from sham animals (n=9), and from STNx rats treated with ramipril (n=9). RNA was extracted from the left ventricle and quantitative real time PCR was used to measure microRNA and their target gene expression levels. Results: In rats with renal injury, there was a significant increase in left ventricular hypertrophy (P&lt;0.05 vs sham). There was also a significant increase in expression of cardiac microRNA-212 (2 fold, P&lt;0.05 vs Sham) and microRNA-132 (3 fold, P&lt;0.05 vs Sham). Ramipril treatment in STNx rats attenuated the increase in microRNA-212 and caused a significant increase in expression of microRNA-133 (P&lt;0.001 vs Sham, P&lt;0.001 vs STNx+Veh) and microRNA-1 (P&lt;0.01 vs Sham, P&lt;0.01 vs STNx+Veh). Renal injury induced left ventricular hypertrophy was attenuated in ramipril treated STNx rats (P&lt;0.001 vs STNx+Veh). We also found altered expression of caspase 9, fibronectin 1, collagen 1A1 and forkhead box O3, all known for their involvement in the regulation of apoptosis, fibrosis and hypertrophy in cardiac cells, whilst being targets for the above microRNAs. Conclusions: The involvement of microRNAs in cardiac pathologies associated with kidney injury is a novel finding of our study. Our finding suggests an involvement of microRNA-1, microRNA-133 and microRNA-212/132 in the cardioprotective action of ACE inhibition in acute kidney injury.
Colchicine and the Heart
Authors: Spyridon Deftereos, Georgios Giannopoulos, Nikolaos Papoutsidakis, Vasiliki Panagopoulou, Charalampos Kossyvakis, Konstantinos Raisakis, Michael W. Cleman, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2013)
The crisis in mental health research
Authors: B S Brown
Journal: American Journal of Psychiatry (1977)

The author states that the mental health research program of the United States is facing a threat to its survival as a force for public health. He describes the antecedents of this crisis, which include the separation of the National Institute of Mental Health from the National Institutes of Health and other organizational changes, the public's disappointment that overly great expectations were not met, and monetary inflation coupled with budgetary cutbacks. He concludes that, because research cannot be separated from the goals of service and training, the success of the total mental health program in the United States depends on resolving the research support crisis.
Who discovers melanoma?
Authors: Howard K. Koh, Donald R. Miller, Alan C. Geller, Richard W. Clapp, Mary Beth Mercer, Robert A. Lew
Journal: Journal of the American Academy of Dermatology (1992)

Background: Melanoma is external and potentially detectable by many persons but little is known about who first discovers these lesions. An understanding of discovery patterns can shape future public and professional education programs. Objective: Our purpose was to assess patterns of melanoma discovery and to determine the patients' role in finding their own lesions. Methods: With a written, mailed questionnaire, we conducted a population-based statewide survey of 216 incident cases of melanoma in Massachusetts. Results: Approximately half (53%) of melanomas were self-discovered, whereas the remainder were detected by medical providers (26%), family members (17%), and others (3%). Nearly one third of persons said they could not see their own lesions easily. Compared with men, women were more likely to discover their own lesions (66% vs 42%, p = 0.001) and those on their spouses (23% vs 2%, p < 0.001). Conclusion: Improving early detection and reducing mortality of melanoma will require both public and professional education programs, with particular emphasis on targeting men at highest risk of this disease. Background: Melanoma is external and potentially detectable by many persons but little is known about who first discovers these lesions. An understanding of discovery patterns can shape future public and professional education programs. Objective: Our purpose was to assess patterns of melanoma discovery and to determine the patients' role in finding their own lesions. Methods: With a written, mailed questionnaire, we conducted a population-based statewide survey of 216 incident cases of melanoma in Massachusetts. Results: Approximately half (53%) of melanomas were self-discovered, whereas the remainder were detected by medical providers (26%), family members (17%), and others (3%). Nearly one third of persons said they could not see their own lesions easily. Compared with men, women were more likely to discover their own lesions (66% vs 42%, p = 0.001) and those on their spouses (23% vs 2%, p < 0.001). Conclusion: Improving early detection and reducing mortality of melanoma will require both public and professional education programs, with particular emphasis on targeting men at highest risk of this disease.