tbuckley/cabot-search huggingface dataset:
Up-regulation of Delta-like 4 Ligand in Human Tumor Vasculature and the Role of Basal Expression in Endothelial Cell Function
Authors: Nilay S. Patel, Ji-Liang Li, Daniele Generali, Richard Poulsom, David W. Cranston, Adrian L. Harris
Journal: Cancer Research (2005)

Abstract The Notch signaling pathway and the delta-like 4 ligand (DLL4) play key roles in embryonic vascular development. Many of the pathways involved in embryonic vascular development also play important roles in tumor angiogenesis. In this study, we assessed the expression of DLL4 in primary renal cancer and investigated the biological function of DLL4 in primary endothelial cells. Using real-time quantitative PCR and in situ hybridization, we showed that the expression of DLL4 was up-regulated within the vasculature of clear cell-renal cell carcinoma almost 9-fold more than normal kidney and was correlated with the expression of vascular endothelial growth factor (VEGF). The expression of DLL4 in endothelial cells was up-regulated by VEGF and basic fibroblast growth factor synergistically, and by hypoxia through hypoxia-inducible factor 1α. Down-regulation of DLL4 expression with RNA interference led to decreased expression of HEY1 and EphrinB2, and the inhibition of endothelial cell proliferation, migration, and network formation, all of which are important processes in tumor angiogenesis. The inhibition of proliferation occurred via the induction of cell cycle arrest in G0-G1 by increased expression of p21 and decreased phosphorylation of retinoblastoma. We conclude that an optimal window of the DLL4 expression is essential for tumor angiogenesis and that selective modulation of the DLL4 expression within human tumors may represent a potential novel antiangiogenic therapy.
Antigenic Studies on Mouse Lymphomas Bearing the T190 Translocation Chromosome&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bertil Bjaring, Urszula Bregula, George Klein, Albert Levan
Journal: JNCI Journal of the National Cancer Institute (1970)

Heterozygous mice of the T190/tf translocation stock, having one superlong and one short marker chromosome, involving the H-2-bearing ninth linkage group, were typed by membrane fluorescence and cytotoxicity tests against a panel of H-2 antisera. Marker-positive segregants differed serologically from their marker-negative siblings. Lymphomas were induced by the Moloney virus in (A.CA x T190/tf)F1 mice. A combined serological and cytogenetic analysis showed that the tumors could be subdivided into two main classes, corresponding to marker-positive and marker-negative types. Each lymphoma was relatively stable with regard to karyologic and correlated antigenic characteristics during serial passage in (A.CA x T190/tf)F1 mice. This system opens new possibilities to study the genetic mechanisms of H-2 antigenic variation, demonstrated previously in heterozygous tumors.
18 PROTEOMIC ANALYSIS IDENTIFIES P90RSK AS A NOVEL THERAPEUTIC TARGET IN PATIENTS WITH ALCOHOLIC HEPATITIS
Authors: O. Morales-Ibanez, M. Moreno, T. Knorpp, M. Templin, C. Millán, J.-C. García-Pagán, V. Arroyo, P. Ginès, J. Caballería, R. Bataller
Journal: Journal of Hepatology (2011)
Behavioral and Clinical Factors Associated With Depression Among Individuals With Diabetes
Authors: Wayne Katon, Michael Von Korff, Paul Ciechanowski, Joan Russo, Elizabeth Lin, Gregory Simon, Evette Ludman, Edward Walker, Terry Bush, Bessie Young
Journal: Diabetes Care (2004)

OBJECTIVE—The goal of this study was to determine the behavioral and clinical characteristics of diabetes that are associated with depression after controlling for potentially confounding variables. RESEARCH DESIGN AND METHODS—A population-based mail survey was sent to patients with diabetes from nine primary care clinics of a health maintenance organization. The Patient Health Questionnaire was used to diagnose depression, and automated diagnostic, pharmacy, and laboratory data were used to measure diabetes treatment intensity, HbA1c levels, and diabetes complications. RESULTS—Independent factors that were associated with a significantly higher likelihood of meeting criteria for major depression included younger age, female sex, less education, being unmarried, BMI ≥30 kg/m2, smoking, higher nondiabetic medical comorbidity, higher numbers of diabetes complications in men, treatment with insulin, and higher HbA1c levels in patients &amp;lt;65 years of age. Independent factors associated with a significantly higher likelihood of meeting criteria for minor depression included younger age, less education, non-Caucasian status, BMI ≥30 kg/m2, smoking, longer duration of diabetes, and a higher number of complications in older (≥65 years) patients. CONCLUSIONS—Smoking and obesity were associated with a higher likelihood of meeting criteria for major and minor depression. Diabetes complications and elevated HbA1c were associated with major depression among demographic subgroups: complications among men and HbA1c among individuals &amp;lt;65 years of age. Older patients with a higher number of complications had an increased likelihood of minor depression.
Radiological Signs of Rheumatoid Arthritis: A Study of Observer Differences in the Reading of Hand Films
Authors: J. H. Kellgren, F. Bier
Journal: Annals of the Rheumatic Diseases (1956)

Radiological changes in the hands and feet have long been considered a useful aid in the diagnosis of rheumatoid arthritis.In a recent study, Fletcher and Rowley (1952) defined these changes in great detail.They confirmed the generally accepted opinion as to the value of surface and pocketed articular erosions, but found osteoporosis difficult to assess even with the help of a control bone as advocated by Steven (1947).Alterations in joint space, though common, may also be difficult to assess.
Transient selection of a hepatitis B virus polymerase gene mutant associated with a decreased replication capacity and famciclovir resistance
Authors: Christian Pichoud, Béatrice Seignères, Zhirui Wang, Christian Trépo, Fabien Zoulim
Journal: Hepatology (1999)

Prolonged therapy for chronic hepatitis B (HBV) with nucleoside analogs may result in the emergence of HBV mutants resistant to antivirals. Here, we describe the transient selection of an HBV polymerase gene mutant that was associated with viral persistence in an immune competent patient treated with famciclovir. Viral polymerase gene sequence was analyzed directly on polymerase chain reaction (PCR) products and also after cloning. The results showed the transient selection of a V542I mutant in the C domain of the viral polymerase. This mutation was associated with a stop codon at amino acid position 199 in the overlapping S gene. The mutated sequence was subcloned in a vector expressing the entire HBV pregenome to study its replication capacity after transient transfection in cultured hepatoma cells. The results showed that the V542I mutant has a decreased replication capacity compared with wild type virus and does not produce HBsAg. The sensitivity of the V542I mutant to penciclovir, the active metabolite of famciclovir, was further studied in tissue culture. This mutant was shown to be resistant to penciclovir, but remained sensitive to lamivudine, as was subsequently observed in vivo . These findings indicate that a prolonged administration of famciclovir may allow for the selection of HBV polymerase gene mutants in immune competent patients. The impaired replication capacity of this V542I mutant may have contributed to the absence of outgrowth of this viral strain in vivo . The study of the in vitro sensitivity of HBV polymerase mutants to nucleoside analogs will be important to design new anti–HBV strategies.(Hepatology 1999;29:230–237.)
Ratio of Waist-to-Calf Circumference and Carotid Atherosclerosis in Korean Patients With Type 2 Diabetes
Authors: Soo-Kyung Kim, Young Ju Choi, Byung Wook Huh, Chul-Sik Kim, Seok Won Park, Eun Jig Lee, Yong-Wook Cho, Kap Bum Huh
Journal: Diabetes Care (2011)

OBJECTIVE To investigate whether waist circumference (WC), calf circumference (CC), and waist-to-calf ratio (WCR) are associated with carotid atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This was an observational study performed in 3,694 Korean patients with type 2 diabetes. Anthropometric measures and carotid ultrasound were performed on each subject. Carotid atherosclerosis was defined as having a clearly isolated focal plaque or mean carotid intima-media thickness (CIMT) ≥1.1 mm. RESULTS CIMT and the frequency of carotid atherosclerosis were higher with increasing WC quartiles and decreasing CC quartiles. There was an augmentative effect of CC and WC on the frequency of carotid atherosclerosis, which was dramatically higher in both the highest WC quartile and lowest CC quartile. However, except for the relationship between the quartile of CC with the frequency of carotid atherosclerosis in men, those associations disappeared after adjusting for potential confounders. In contrast, WCR was significantly related to CIMT (only in women) and carotid atherosclerosis, even after adjustment (adjusted odds ratio for carotid atherosclerosis for the highest quartile of WCR compared with the lowest quartile being 1.178 [95% CI 1.026–1.353] and 1.276 [1.053–1.545] in men and women, respectively). CONCLUSIONS A low CC and high WC seems to be associated with a carotid atherosclerotic burden in Korean diabetic patients. In particular, compared with each circumference, WCR is independently associated with carotid atherosclerosis. However, the cross-sectional nature of the study limits conclusions regarding the direction or causality. Further longitudinal study is warranted in this and other ethnic groups.
Perforin and Fas killing by CD8+ T cells limits their cytokine synthesis and proliferation.
Authors: S Sad, D Kägi, T R Mosmann
Journal: The Journal of Experimental Medicine (1996)

During an immune response, effector CD8+ T cells can kill infected cells by the perforin-dependent pathway. In comparison to CD4+ T cells, which are major sources of cytokines, normal CD8+ T cells produced less interleukin 2 and interferon gamma, and proliferated less vigorously after antigenic stimulation. Killing of target cells was a major cause of these reduced responses, since perforin-deficient CD8+ T cells showed substantially increased cytokine synthesis and proliferation. Cytotoxicity by the alternate Fas pathway also resulted in self-limitation of CD8+ T cell cytokine synthesis. This relationship between cytotoxicity and cytokine synthesis may regulate CD8+ T function in different phases of an immune response.
Prognostic Value of Ultrasonographic Measurement of Carotid Intima Media Thickness in Dialysis Patients
Authors: FRANCESCO ANTONIO BENEDETTO, FRANCESCA MALLAMACI, GIOVANNI TRIPEPI, CARMINE ZOCCALI
Journal: Journal of the American Society of Nephrology (2001)

High-resolution carotid ultrasonography is considered a fundamental technique for the investigation of the vascular system. However, it is still very unclear whether ultrasonographic studies of carotid arteries are useful for the prediction of cardiovascular events in patients with end-stage renal disease. The prediction power of carotid ultrasonography for all-cause and cardiovascular mortality was tested in a cohort of 138 patients receiving chronic dialysis treatment (91 receiving hemodialysis treatment and 47 receiving continuous ambulatory peritoneal dialysis treatment; follow-up, 29.8 ± 15.0 mo), and the relationship between this parameter and alterations in left ventricular mass (LVM) and geometry was examined. On univariate analysis, intima media thickness (IMT) was directly related to LVM as well as to the absolute and relative thicknesses of LV walls but independent of LV end-diastolic volume. Data analysis based on LV geometry patterns revealed that patients with concentric hypertrophy were those with the highest IMT. The internal diameter of the common carotid artery (DCCA) was also related to concentric hypertrophy, but the strength of this relationship was of borderline significance (P = 0.06). During the follow-up period, 63 patients died: 32 (51%) of them of cardiovascular causes. IMT was significantly higher (P = 0.006) in patients who died of cardiovascular causes (1.10 ± 0.21 mm) than in patients who survived (0.99 ± 0.24 mm), In a Cox regression model, this parameter turned out to be an independent predictor of cardiovascular death, and it retained an independent effect in a model that included LVM. Treatment modality failed to independently predict this outcome. The risk of cardiovascular death was progressively higher from the first IMT tertile onward. DCCA failed to predict cardiovascular outcomes. IMT in dialysis patients is associated with LV concentric hypertrophy and is an independent predictor of cardiovascular death. IMT may be usefully applied for risk stratification in the dialysis population.
The Model State Emergency Health Powers Act
Authors: Lawrence O. Gostin, Jason W. Sapsin, Stephen P. Teret, Scott Burris, Julie Samia Mair, James G. Hodge, Jr, Jon S. Vernick
Journal: JAMA (2002)

The Center for Law and the Public's Health at Georgetown and Johns Hopkins Universities drafted the Model State Emergency Health Powers Act (MSEHPA or Model Act) at the request of the Centers for Disease Control and Prevention. The Model Act provides state actors with the powers they need to detect and contain bioterrorism or a naturally occurring disease outbreak. Legislative bills based on the MSEHPA have been introduced in 34 states. Problems of obsolescence, inconsistency, and inadequacy may render current state laws ineffective or even counterproductive. State laws often date back to the early 20th century and have been built up in layers over the years. They frequently predate the vast changes in the public health sciences and constitutional law. The Model Act is structured to reflect 5 basic public health functions to be facilitated by law: (1) preparedness, comprehensive planning for a public health emergency; (2) surveillance, measures to detect and track public health emergencies; (3) management of property, ensuring adequate availability of vaccines, pharmaceuticals, and hospitals, as well as providing power to abate hazards to the public's health; (4) protection of persons, powers to compel vaccination, testing, treatment, isolation, and quarantine when clearly necessary; and (5) communication, providing clear and authoritative information to the public. The Model Act also contains a modernized, extensive set of principles and requirements to safeguard personal rights. Law can be a tool to improve public health preparedness. A constitutional democracy must balance the common good with respect for personal dignity, toleration of groups, and adherence to principles of justice.
Macrophage-Targeted Overexpression of Urokinase Causes Accelerated Atherosclerosis, Coronary Artery Occlusions, and Premature Death
Authors: Aaron E. Cozen, Hideaki Moriwaki, Michal Kremen, Mary Beth DeYoung, Helén L. Dichek, Katherine I. Slezicki, Stephen G. Young, Murielle Véniant, David A. Dichek
Journal: Circulation (2004)

Background— Human atherosclerotic lesions contain elevated levels of urokinase plasminogen activator (uPA), expressed predominantly by macrophages. Methods and Results— To test the hypothesis that macrophage-expressed uPA contributes to the progression and complications of atherosclerosis, we generated transgenic mice with macrophage-targeted overexpression of uPA. The uPA transgene was bred into the apolipoprotein E–null background, and transgenic mice and nontransgenic littermate controls were fed an atherogenic diet. uPA-transgenic mice had significantly elevated uPA activity in the atherosclerotic artery wall, of a magnitude similar to elevations reported in atherosclerotic human arteries. Compared with littermate controls, uPA-transgenic mice had accelerated atherosclerosis, dilated aortic roots, occlusive proximal coronary artery disease, myocardial infarcts, and early mortality. Conclusions— These data support the hypothesis that overexpression of uPA by artery wall macrophages is atherogenic and suggest that uPA inhibitors might be therapeutically useful.
The appropriate use of non-steroidal anti-inflammatory drugs in rheumatic disease: opinions of a multidisciplinary European expert panel
Authors: G. Burmester, A. Lanas, L. Biasucci, M. Hermann, S. Lohmander, I. Olivieri, C. Scarpignato, J. Smolen, C. Hawkey, A. Bajkowski, F. Berenbaum, F. Breedveld, P. Dieleman, M. Dougados, T. MacDonald, E. M. Mola, T. Mets, N. Van Den Noortgate, H. Stoevelaar
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Introduction</h3> Given the safety issues of non-steroidal anti-inflammatory drugs (NSAID) and the robustness of guidelines, making treatment choices in daily clinical practice is increasingly difficult. This study aimed systematically to analyse the opinions of a multidisciplinary European expert panel on the appropriateness of different NSAID, with or without the use of a proton pump inhibitor (PPI), in individual patients with chronic rheumatic disease. <h3>Methods</h3> Using the Research and Development/University of California at Los Angeles appropriateness method, the appropriateness of five (non-)selective NSAID with or without a PPI was assessed for 144 hypothetical patient profiles, ie, unique combinations of cardiovascular and gastrointestinal risk factors. Appropriateness statements were calculated for all indications. <h3>Results</h3> All options without PPI were considered appropriate in patients with no gastrointestinal/cardiovascular risk factors. Cyclooxygenase-2 selective inhibitors (C2SI) alone and non-selective NSAID plus PPI were preferred for patients with elevated gastrointestinal risk and low cardiovascular risk. Naproxen plus PPI was favoured in patients with high cardiovascular risk. For the combination of high gastrointestinal/high cardiovascular risk the use of any NSAID was discouraged; if needed, naproxen plus PPI or a C2SI plus PPI could be considered. <h3>Discussion</h3> The panel results may support treatment considerations at the level of individual patients, according to their gastrointestinal/cardiovascular risk profile.
Biomarkers to exclude the diagnosis of ventilator-associated pneumonia
Authors: Michael A Matthay
Journal: Thorax (2014)

Biomarkers to exclude the diagnosis of ventilator-associated pneumonia Michael A MatthayVentilator-acquired pneumonia (VAP) is an important clinical problem that has been associated with substantial morbidity and mortality. 1However, the diagnosis of VAP can be particularly difficult, 2-4 and surveillance programmes have not been markedly successful. 5 6The diagnosis of VAP can be
Depressive Symptoms and the Cost of Health Services in HMO Patients Aged 65 Years and Older
Authors: J Unützer, D L Patrick, G Simon, D Grembowski, E Walker, C Rutter, W Katon
Journal: JAMA (1997)

To examine whether depressive symptoms in older adults contribute to increased cost of general medical services.A 4-year prospective cohort study.Four primary care clinics of a large staff-model health maintenance organization (HMO) in Seattle, Wash.A total of 5012 Medicare enrollees older than 65 years were invited to participate in the study; 2558 subjects (51%) were successfully enrolled. Non-participants were somewhat older and had a higher level of chronic medical illness.Depressive symptoms as measured by the Center for Epidemiological Studies Depression scale, which was administered as part of a mail survey at baseline, at 2 years, and at 4 years; and total cost of medical services from the perspective of the HMO. Data were obtained from the cost accounting system of the HMO.In this cohort of older adults, depressive symptoms were common, persistent, and associated with a significant increase in the cost of general medical services. This increase was seen for every component of health care costs and was not accounted for by an increase in specialty mental health care. The increase in health care costs remained significant after adjusting for differences in age, sex, and chronic medical illness.Depressive symptoms in older adults are associated with a significant increase in the cost of medical services, even after adjusting for the severity of chronic medical illness.
<b> <i>Skp2</i> </b> Gene Copy Number Aberrations Are Common in Non-Small Cell Lung Carcinoma, and Its Overexpression in Tumors with <b> <i>ras</i> </b> Mutation Is a Poor Prognostic Marker
Authors: Chang Qi Zhu, Fiona H. Blackhall, Melania Pintilie, Pratibha Iyengar, Ni Liu, James Ho, Taylor Chomiak, Davina Lau, Timothy Winton, Frances A. Shepherd, Ming-Sound Tsao
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Skp2 plays a critical role in cell cycle progression, especially at the G1-S transition, putatively through its control of several cell cycle regulator proteins. The Skp2 gene is located on a region of chromosome 5p that is commonly overrepresented in lung cancer. The present study aimed to evaluate Skp2 abnormalities and their prognostic value in non-small cell lung cancer (NSCLC). Experimental Design: In total 16 NSCLC cell lines and 163 primary tumors were included in studies to measure Skp2 relative gene copy number, mRNA abundance, and protein level. The tumors were also evaluated for p27 protein expression level and ras mutation. These values were correlated with the clinical and pathological features of the patients. Results: Skp2 relative gene copy number aberrations were found in 88 and 65% of NSCLC cell lines and primary tumors, respectively. Overrepresentation was especially common among squamous cell carcinoma (74%). Both gene copy overrepresentation (13%) and loss (35%) were found in adenocarcinoma. Skp2 relative gene copy number was significantly correlated with mRNA and protein levels, but none of these were correlated with p27 protein levels. Neither high Skp2 protein expression nor ras mutation was prognostically significant. In NSCLCs with ras mutation, however, high Skp2 protein expression was a significant independent poor prognostic marker. Conclusion: There appears to be a synergistic interaction between high Skp2 protein expression and ras mutation with negative impact on the survival of NSCLC patients.
Alternative Markers of Hyperglycemia and Risk of Diabetes
Authors: Stephen P. Juraschek, Michael W. Steffes, Edgar R. Miller, Elizabeth Selvin
Journal: Diabetes Care (2012)

OBJECTIVE Fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) are of interest for monitoring short-term glycemic control in patients with diabetes; however, their associations with diabetes risk are uncharacterized. RESEARCH DESIGN AND METHODS We used Cox proportional hazards models to examine the associations of fructosamine, glycated albumin, and 1,5-AG with incident diabetes in 1,299 participants, from the Atherosclerosis Risk in Communities (ARIC) Study (2005–2006), who had no history of diagnosed diabetes at baseline. Incident diabetes was self-reported during annual telephone calls. RESULTS There were 119 new cases of diabetes during a median follow-up of 3.3 years. When compared with the lowest quartile, the fourth quartiles of fructosamine and glycated albumin were significantly associated with diabetes risk (hazard ratio [HR] 3.99 [95% CI 1.93–8.28] and 5.22 [2.49–10.94], respectively). The fourth quartile of 1,5-AG was associated with a significantly lower diabetes risk (0.27 [0.14–0.55]). Associations were attenuated but still significant after adjustment for hemoglobin A1c (A1C) or fasting glucose. CONCLUSIONS Fructosamine, glycated albumin, and 1,5-AG were associated with the subsequent development of diabetes independently of baseline A1C and fasting glucose. Our results suggest these alternative biomarkers may be useful in identifying persons at risk for diabetes.