tbuckley/cabot-search huggingface dataset:
690. Angiopoietin-1 Reduces Lung Edema and Mortality Induced by Bacterial Endotoxin
Authors: Yao Qi Huang, Harald Sauthoff, Teona Pipiya, Shu Chen, William N. Rom, John G. Hay
Journal: Molecular Therapy (2004)

Acute lung injury (ALI) is a frequent cause of morbidity and mortality in patients with bacterial sepsis. Capillary leakage together with interstitial and alveolar edema are the hallmarks of this condition. The loss of integrity in the endothelial barrier is a prerequisite for development of ALI. Angiopoietin-1 (Ang-1) binds to the Tie2 receptor. This interaction activates the phosphatidylinositol 3′-kinase/Akt survival pathway that promotes endothelial cell integrity and survival. Ang-1 has also been shown to reduce vascular permeability and vessel leakage induced by a variety of factors including VEGF and thrombin. We hypothesized that in an animal model of ALI, inducing Ang-1 expression would stabilize vessels and attenuate capillary leakage, thereby reducing lung edema formation. We therefore examined the effects of Ang-1 expression in a murine model of ALI. Ang-1 expression was induced by infection with a non-replicating adenoviral vector containing the Ang-1 cDNA (AdAng1). AdAng1 or a control E1a/E1b deleted adenovirus (Ad312) was injected by intraperitoneal injection (1×109 PFU) into C57BL/6 mice. Ang-1 was detectable in the serum by immunoblotting at day 4. Five days later, a single dose of endotoxin was given by intraperitoneal injection. At 24 hours following endotoxin administration, Evans blue was injected intravenously. Lung edema was evaluated by measuring the leakage of Evans blue into the lung. The concentration of Evans blue detected in the lung was increased in endotoxin treated mice compared to saline controls (0.72 se 0.11 vs. 0.37 se 0.01 OD units), suggesting capillary leakage. However, the level of Evans blue detected in the lung was lower in mice pretreated with AdAng1 than in mice pretreated with the control adenovirus (0.45 se 0.01 vs. 0.73 se 0.06 OD units). Furthermore, AdAng1 was effective in reducing the mortality associated with endotoxin administration. At 36 hours after endotoxin administration, all of the saline treated controls (n5) and all of the Ad312 treated controls (n5) had died. In contrast, all of the AdAng1 treated animals were alive at 36 hours, and 4 of 5 were still alive at 7 days. These data suggest that pre-treatment with Ang-1 protects against the development of lung edema and also decreases the mortality induced by endotoxin.
718. Systemic Gene Transfer to Striated Muscles Using rAAV6 Vectors
Authors: Paul Gregorevic, Michael J. Blankinship, James M. Allen, Leonard Meuse, Jay Han, Suzanne Oakley, Jeffrey S. Chamberlain
Journal: Molecular Therapy (2004)

Human mortality is severely affected by diseases of the cardiac and skeletal musculature. Genetic interventions are being developed for these diseases, but are limited by an inability to achieve widespread gene transfer to the heart and numerous skeletal muscles of an adult mammal. We have observed that recombinant adeno-associated viral vectors (rAAV vectors) comprising serotype type 6 capsid proteins potently transduce striated muscles following direct intramuscular injection. In subsequent experiments we have identified procedures for administering rAAV6 vectors intravascularly to conscious adult mice that achieve high-level transgene expression (up to 8,000 fold increases in indices over control values) in the vast majority of cardiac and skeletal muscle fibers. These data are the first to demonstrate that extensive transduction of both the cardiac and skeletal musculature is achievable in an adult mammal using a single, minimally invasive intravenous injection of rAAV6 vectors. We have observed that transgene expression in striated muscle fibers following vector administration is influenced by the design of the expression cassette delivered and present data demonstrating that muscle-restricted transgene expression reduces the incidence of immunological reaction against the transgene product compared with a constitutively-driven expression cassette. To assess the therapeutic potential of these novel gene delivery techniques, we have begun administering rAAV6 vectors containing therapeutic expression cassettes to murine models of Duchenne muscular dystrophy. Treated dystrophic mdx mice exhibit widespread expression of therapeutic dystrophin-based proteins throughout the striated musculature in a manner that is sufficient to reduce pathological features of the dystrophic phenotype, including susceptibility to contraction induced injury, and serum creatine kinase (an indicator of muscle degeneration). Having established a method of facilitating widespread gene delivery throughout the muscles of adult mice, we are now evaluating modifications of these techniques for increased gene delivery efficiency. Here we summarize our understanding of the factors influencing rAAV-mediated systemic gene delivery to striated muscles, and the therapeutic potential of such techniques for the treatment of muscular dystrophies.
Detection ofBCL-6 rearrangements andp53 mutations in malt-lymphomas
Authors: Gianluca Gaidano, Gisella Volpe, Cristina Pastore, Roberto Chiarle, Daniela Capello, Annunziata Gloghini, Eliana Perissinotto, Francesco Savinelli, Martino Bosco, Umberto Mazza, Stefano Pileri, Giorgio Palestro, Antonino Carbone, Giuseppe Saglio
Journal: American Journal of Hematology (1997)

Twenty-seven lymphomas of mucosa-associated lymphoid tissue (MALT) derived from distinct anatomical sites were tested for the presence of genetic lesions commonly involved in B-cell lymphomagenesis, including activation of proto-oncogenes (BCL-1, BCL-2, BCL-6, and c-MYC), disruption of tumor suppressor loci (p53, 6q), and infection by viruses [Epstein-Barr virus (EBV), and Kaposi's sarcoma-herpesvirus/human herpesvirus-8 (KSHV/HHV-8)]. Sixteen low-grade and 11 high-grade MALT-lymphomas were included in the study. The presence of genetic lesions was tested by a combination of molecular approaches, including Southern blot hybridization, polymerase chain reaction (PCR), and PCR-single strand conformation polymorphism followed by DNA direct sequencing. Alterations of BCL-1, BCL-2, or c-MYC, as well as infection by KSHV/HHV-8, scored negative in all MALT-lymphomas analysed. Conversely, rearrangements of BCL-6 and mutations of p53 clustered with a fraction of high-grade MALT-lymphomas. Deletions of 6q occurred in selected cases of both low- and high-grade MALT-lymphomas, whereas a monoclonal infection by EBV was restricted to one single patient. These data corroborate the notion that the molecular pathogenesis of MALT-lymphomas differs substantially from that of nodal B-cell lymphomas. Occasionally, however, a proportion of high-grade MALT-lymphomas may harbor selected genetic lesions among the ones commonly involved in nodal B-cell lymphomagenesis. Am. J. Hematol. 56:206–213, 1997. © 1997 Wiley-Liss, Inc.
Abstract 17480: Safety and Efficacy of Continuous Anticoagulant and Antiplatelet Combination Therapy during Implantation of Cardiac Rhythm Devices
Authors: Kohei Ishibashi, Koji Miyamoto, Mitsuru Wada, Ikutaro Nakajima, Hideo Okamura, Takashi Noda, Takeshi Aiba, Hiroshi Takaki, Shiro Kamakura, Masaharu Ishihara, Toshihisa Anzai, Satoshi Yasuda, Hisao Ogawa, Kengo Kusano
Journal: Circulation (2014)

Introduction: Previous studies showed that continuous anticoagulation during implantation of cardiac rhythm device (CRD) was safe. However, the safety and efficacy of continuous anticoagulant and antiplatelet combination therapy in patients undergoing CRD interventions has not been clearly defined. Hypothesis: We sought to evaluate the safety and efficacy of this therapy during implantation of CRD. Methods: A total of consecutive 300 patients (mean 68.7 years old, 171 males) underwent CRD implantation were enrolled from April 2012 to December 2012. We divided patients into Non-drug (patients without antithrombotic therapy), Single-drug (patients with anticoagulant or antiplatelet therapy), and Combination-drug (patients with anticoagulant and antiplatelet therapy) group, and evaluated the clinical outcome among 3 groups. Clinically significant hematoma was defined as device-pocket hematoma that needed prolonged hospitalization, interruption of antithrombotic therapy, surgical intervention, or blood products transfusion. Results: The number of Non-drug, Single-drug, and Combination-drug groups was 129, 139, and 32, respectively. Clinical outcome was shown in Table. Hematoma occurred significantly more in Combination-drug than Non-drug group, but occurrence of clinically significant hematoma was not different among 3 groups. Cardiac tamponade was none and thrombo-embolic event was rare. Conclusions: Continuous anticoagulant and antiplatelet combination therapy was safe and effective during implantation of CRD.
Portrait of a Merchant
Authors: M. Therese Southgate
Journal: JAMA (2001)

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
Assuring the Quality of Health Care for Older Persons
Authors: Arlene Fink
Journal: JAMA (1987)

To select topics for quality assurance activities focusing on older patients, we convened a 14-member panel of physicians and experts in quality assurance. In two rounds of ratings, panelists rated 42 medical conditions (eg, pneumonia) in terms of their effects on patient outcomes, the availability of beneficial interventions, and the health benefits from improving current quality. They rated 27 health services (eg, adult day-care) on similar dimensions. The feasibility of doing quality assurance work on each condition and service also was rated. Using the ratings, the conditions selected for quality assurance work were congestive heart failure, hypertension, pneumonia, breast cancer, adverse effects of drugs, incontinence, and depression. Health care services selected were hospital discharge planning, acute inpatient care for the frail elderly, long-term—care facilities (intermediate-care facilities and skilled nursing facilities), home health care services, and case management. (<i>JAMA</i>1987;258:1905-1908)
Abstract P332: Framingham Risk Score to Predict Subsequent Coronary Artery Calcification in a Young Adult Population
Authors: Jia Pu, Dave Vanness, Heather Johnson, David Kreling, Henry Young, Betty Chewning
Journal: Circulation (2014)

Introduction: Coronary artery calcification (CAC) has been identified as an independent predictor of coronary events, suggesting the potential use of CAC for risk assessment in asymptomatic individuals. However, ionizing radiation exposure associated with CAC CT scans remains a concern. If elevated risk for developing subclinical cardiovascular disease (CVD) could be identified based on less invasive risk assessment, such as the Framingham risk score, intensified prevention and screening services could be provided to this targeted population. Hypothesis: This study aims to assess the association between the Framingham risk score in early adulthood and subsequent subclinical CVD measured by CAC. Additional risk factors including demographics, socioeconomic status and health behaviors were tested in terms of their capabilities to enhance prediction of subclinical CVD beyond the Framingham risk score. Methods: This study used the Coronary Artery Risk Development in Young Adults (CARDIA) data, with a total of 5,115 Caucasian and African American males and females. Information collected at examination year 10 was used to calculate the Framingham risk score. CAC was measured ten years later (examination year 20). Participants’ demographics, health behaviors (alcohol consumption, BMI, and exercise), socioeconomic status and medical needs at year 10 were identified as potential risk factors associated with the subsequent presence of CAC beyond the Framingham risk score. Multiple logistic regression was used to examine the adjusted association between CAC, Framingham risk score and proposed risk factors. Model comparison was estimated using the area under the receiver operating characteristic curve (AUC) and Akaike information criterion (AIC). Results: By year 20, CAC was present in 19% of the CARDIA population. The Framingham risk score in young adulthood was strongly associated with the subsequent presence of CAC ten years later, regardless of race and gender. Overall, 42% of the CARDIA participants with elevated Framingham risk scores at year 10 had CAC at year 20, compared to 16% of participants with normal scores. The Framingham risk score may underestimate the risk of CAC for males compared to females (Negative Predictive Value: 75% vs. 91%). Beyond the Framingham risk score, the subsequent presence of CAC was associated with being overweight or obese in all populations, at-risk alcohol consumption in African American males, and having high school level or lower education and financial hardship in African American females. Conclusions: Our findings support the potential use of the Framingham risk score as a screening tool for subsequent subclinical atherosclerosis in a young adult population. However, other gender-specific risk factors beyond the Framingham risk score such as obesity also may be important to better predict subclinical CVD risk, especially in male populations.
Report Describes Trends in US Cancer Incidence and Mortality Rates
Authors: Tracy Hampton
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa
Authors: Jo-David Fine, Eugene A. Bauer, Robert A. Briggaman, D. Martin Carter, Robin A.J. Eady, Nancy B. Esterly, Karen A. Holbrook, Sidney Hurwitz, Lorraine Johnson, Andrew Lin, Roger Pearson, Virginia P. Sybert
Journal: Journal of the American Academy of Dermatology (1991)
Abstract 13689: Effectiveness of Paclitaxel-eluting Balloon Catheter in Patients with Sirolimus-eluting Stent Restenosis: Results of a Prospective, Single-blind, Randomized Study.
Authors: Seiji Habara, Kazuaki Mitsudo, Kazushige Kadota, Tsuyoshi Goto, Satoki Fujii, Hiroyuki Yamamoto, Harumi Katoh, Naoki Oka, Yasushi Fuku, Shingo Hosogi, Akitoshi Hirono, Takeshi Maruo, Hiroyuki Tanaka, Yoshikazu Shigemoto, Daiji Hasegawa, Hiroshi Tasaka, Mana Kusunose, Suguru Otsuru, Yoji Okamoto, Naoki Saito, Yuki Tsujimoto
Journal: Circulation (2010)

Background: As drug-eluting stents (DESs) are being used in increasingly complicated settings, DES restenosis is no longer an uncommon phenomenon, and its optimal treatment is not known. Methods an...
Development of a comorbidity index that reflects health-related quality of life in patients with COPD
Authors: Anja Frei, Patrick Muggensturm, Lara Siebeling, Marco Zoller, Cynthia Boyd, Gerben ter Riet, Milo Puhan
Journal: European Respiratory Journal (2011)

Background: In COPD research little consideration is currently given to the impact of co-existing comorbidities, which is partly due to the absence of an index that would quantify their impact. We developed a COPD comorbidity index that quantifies the impact on health-related quality of life (HRQL).

Methods: Using data from 411 Swiss and Dutch COPD patients with GOLD stages ≥2 we used the non-COPD specific Feeling Thermometer (FT, scores 0-100) as a valid and reliable instrument to measure HRQL. We ascertained the presence of comorbidities that may impact on HRQL through self-report and chart review. In the analysis, we used specific comorbidities if their prevalence was ≥5% and summarized rarer comorbidities by disease groups (e.g. psychiatric disease). We included theses diseases in multivariate linear regression models if their association with the FT was ≥3 points (=0.5 minimal important difference) in univariate analysis adjusted for FEV1.

Results: Coronary heart disease (p=0.018), diabetes (p=0.009), psychiatric disease (p=0.017) and urogenital disease (p=0.018) were most strongly associated with HRQL in the final multivariate model, which was then transformed into an index ranging from 0-4 where each disease counted equally. An increase of one disease count was associated with a decrease in HRQL of -4.54 on the FT (95% CI -6.34 to -2.74, p<0.001).

Conclusion: A simple index that counts the presence of four comorbidities can be used to quantify the impact of comorbidities in COPD patients in research and practice.
Abstract 5567: Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC)
Authors: Erard Gilles, Jacques Bosq, Laura Caplier, Alice Bexon, Alexander Zukiwski, Jacques Bonneterre
Journal: Cancer Research (2014)

Abstract Background: Given the poor therapeutic outcomes for triple negative BC, diagnostic accuracy is vital. In routine IHC, PR is measured using bispecific antibodies (Ab) that recognize epitopes common to PRA and PRB. PR A and B expression is imbalanced in BC. Relative expression of the PR isotypes appears to be prognostic in tumors evaluated with a bispecific Ab (Hopp 2004). Tumors can express PRA or PRB on different cells in the same tumor (Mote 2008), which differ from those expressing ERα (Zukiwski 2013). A true triple negative phenotype might escape detection with the use of one single Ab to detect both PR A and B epitopes, depending on its sensitivity/specificity. This study evaluated the use of two isotype-specific PR Abs to fully characterize PR status. Methods: 312 archived BC specimens with clinical data came from Oscar Lambret Cancer Center, Lille. HER2 status was previously determined. IHC was performed using anti-ERα, anti-PRA and PRB Abs. ERα and PR tumor positivity was defined as ≥ 1% stained tumor cells. Results: 276 cases had complete data. Table 1 shows ERα, PRA and PRB status. 38/276 cases (14%) were ERα and HER2 negative: 22 were PR A or B negative, 9 were PR A and B positive, 2 were positive only for PRA and 5 only for PRB. Discussion: Bispecific PR Abs rarely report PRA and PRB similarly (Mote 2001). PR Phosphorylation and activation may vary across tumors. Potentially only one PR isotype may drive BC tumor growth. Triple-negative BC status determination could be PR Ab-dependent. These cases are currently being tested with a standard bispecific PR Ab to understand which would be considered triple-negative with routine IHC. Conclusion: Further evaluation of IHC with specific PRA and PRB Abs is warranted to determine if certain patients, currently classified as having triple-negative BC, could respond to antiprogestins, which have shown activity in BC. Table 1% of276 casesPR (PRA or PRB)PRAPRBERαNegativePositiveTotalNegativePositiveTotalNegativePositiveTotalNegative148221742115722Positive77178146579106868Total217910031691002575100 Citation Format: Erard Gilles, Jacques Bosq, Laura Caplier, Alice Bexon, Alexander Zukiwski, Jacques Bonneterre. Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC). [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 5567. doi:10.1158/1538-7445.AM2014-5567
Abstract 20478: Circulating Inflammatory Potential Measured by an Endothelial Biosensor Assay in Coronary Artery Disease Patients
Authors: Heidi Cung, Joe Anderson, James Nawarskas, Matthew Campen
Journal: Circulation (2014)

Introduction: Vascular disease is driven by systemic inflammation that can arise from sites distal to the affected coronary or cerebral vessels. The objective of this study is to characterize the inflammatory potential of serum from patients with coronary artery disease (CAD) using cultured endothelial cells as a biosensor of the circulating milieu. Methods: Serum samples from CAD patients (N=48) and healthy control subjects (N=50) were incubated with primary human coronary artery endothelial cells at a 1:10 dilution for 4h, following by isolation of the cellular RNA. Alteration of inflammation-responsive elements (adhesion molecules and cytokines) was assessed on a gene expression level. Specific indicators included intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM), and interleukin-8 (IL-8). Additionally, the serum samples from the CAD patients and healthy individuals were quantitatively analyzed for IL-1β, IL-6, IL-8, and TNF-α using an electrochemical luminescence platform. Results: For the CAD subjects’ serum, the mean values of ICAM, VCAM, and IL-8 expression were all elevated compared to healthy control subjects (p&lt;0.001 for each by Students T-test). Correlational analysis revealed the three indicators (ICAM, VCAM, and IL-8) to be independent of each other and also other inflammatory markers such as C-reactive protein. IL-8 expression was negatively correlated with serum HDL levels but positively correlated with body fat composition. Interestingly, serum levels of IL-1β, IL-6, IL-8, and TNF-α in CAD patients were not statistically different from healthy control subjects. Conclusions: As yet uncharacterized circulating factors in the serum of CAD patients appear to activate endothelial cells. This assay paradigm performed well in terms of discriminating patients with CAD compared to healthy subjects, with greater range and specificity than specific inflammatory markers.