tbuckley/cabot-search huggingface dataset:
Glycoproteomic Study Reveals Altered Plasma Proteins Associated with HIV Elite Suppressors
Authors: Weiming Yang, Oliver Laeyendecker, Sarah K. Wendel, Bai Zhang, Shisheng Sun, Jian-Ying Zhou, Minghui Ao, Richard D. Moore, J. Brooks Jackson, Hui Zhang
Journal: Theranostics (2014)

HIV elite suppressors (ES) or controllers are individuals achieving control of viremia by their natural immunological mechanisms without highly active antiretroviral therapy (HAART). Study of the mechanisms responsible for the immunological suppression of viremia in ES may lead to the detection of individuals with ES and the effective control of HIV infection. We hypothesize that plasma glycoproteins play essential roles in the immune system of ES since plasma proteins are critical and highly relevant in anti-viral immunity and most plasma proteins are glycoproteins. To examine glycoproteins associated with ES, plasma samples from ES individuals (n=20), and from individuals on HAART (n=20), with AIDS (n=20), and no HIV infection (n=10) were analyzed by quantitative glycoproteomics. We found that a number of glycoproteins changed between ES versus HAART, AIDS and HIV- individuals. In sharp contrast, the level of plasma glycoproteins in the HAART cohort showed fewer changes compared with AIDS and HIV- individuals. These results showed that although both ES and HAART effectively suppress viremia, ES appeared to profoundly affect immunologically relevant glycoproteins in plasma as consequence of or support for anti-viral immunity. Bioinformatic analysis revealed that altered proteins in ES plasma were mainly associated with inflammation. This analysis suggests that overlapping, while distinguishable, glycoprotein profiles for inflammation and immune activation appeared to be present between ES and non-ES (HAART+AIDS) cohorts, indicating different triggers for inflammation and immune activation between natural and treatment-related viral suppression.
Effects of Telmisartan, Ramipril, and Their Combination on Left Ventricular Hypertrophy in Individuals at High Vascular Risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease
Authors: Paolo Verdecchia, Peter Sleight, Giuseppe Mancia, Robert Fagard, Bruno Trimarco, Roland E. Schmieder, Jae-Hyung Kim, Garry Jennings, Petr Jansky, Jyh-Hong Chen, Lisheng Liu, Peggy Gao, Jeffrey Probstfield, Koon Teo, Salim Yusuf
Journal: Circulation (2009)

Background— Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers reduce left ventricular hypertrophy (LVH). The effect of these drugs on LVH in high-risk patients without heart failure is unknown. Methods and Results— In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), patients at high vascular risk and tolerant of ACE inhibitors were randomly assigned to ramipril, telmisartan, or their combination (n=23 165). In the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND), patients intolerant of ACE inhibitors were randomized to telmisartan or placebo (n=5343). Prevalence of LVH at entry in TRANSCEND was 12.7%. It was reduced by telmisartan (10.5% and 9.9% after 2 and 5 years) compared with placebo (12.7% and 12.8% after 2 and 5 years) (overall odds ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P =0.0017). New-onset LVH occurred less frequently with telmisartan compared with placebo (overall odds ratio, 0.63; 95% CI, 0.51 to 0.79; P =0.0001). LVH regression was similar in the 2 groups. In ONTARGET, prevalence of LVH at entry was 12.4%. At follow-up, it occurred slightly less frequently with telmisartan (odds ratio, 0.92; 95% CI, 0.83 to 1.01; P =0.07) and the combination (odds ratio, 0.93; 95% CI, 0.84 to 1.02; P =0.12) than with ramipril, but differences between the groups were not significant. New-onset LVH was associated with a higher risk of primary outcome during follow-up (hazard ratio, 1.77; 95% CI, 1.50 to 2.07). Conclusions— In patients at high vascular risk, telmisartan is more effective than placebo in reducing LVH. New-onset LVH is reduced by 37%. The effect of combination of the 2 drugs on LVH is similar to that of ramipril alone.
Can we rely on magnetic resonance imaging when evaluating unstable atlantoaxial subluxation?
Authors: K Laiho, I Soini, H Kautiainen, M Kauppi
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> To examine whether functional radiography and functional magnetic resonance imaging (MRI) are equally efficient in detecting the extent of unstable anterior atlantoaxial subluxation (aAAS) in rheumatic patients. <b>Methods:</b> 23 patients with unstable aAAS (diagnosed by functional radiography) were examined by functional MRI because of a neck symptom. Twenty two patients had rheumatoid arthritis and one had juvenile idiopathic arthritis. aAAS was diagnosed if the anterior atlantoaxial diameter (AAD) was &gt;3 mm and was considered unstable if the AAD differed by &gt;2 mm between flexion and extension radiographs. The AAD was measured from radiographs (flexion and extension) and MRI images (flexion and neutral). <b>Results:</b> The extent of aAAS during flexion measured by radiography was greater than that found by MRI in all 23 patients (mean difference 3 mm (95% confidence interval 2 to 4)). In four (17%) patients flexion MRI could not demonstrate aAAS detected by radiography. The difference between the AAD measurements during flexion by these two methods was substantial (that is, ⩾4 mm) in nine (39%) cases. Severe aAAS (⩾9 mm) was seen in 15 (65%) patients by functional radiography and in four (17%) by functional MRI. <b>Conclusions:</b> The magnitude of aAAS was often substantially smaller when measured by functional MRI rather than by functional radiography. Thus one cannot rely on the result of functional MRI alone; functional radiographs are needed to show the size of unstable aAAS. The maximal extent of the subluxation must be taken into account when the possible compression of neural structures is evaluated by MRI.
Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock
Authors: Holger Thiele, Uwe Zeymer, Franz-Josef Neumann, Miroslaw Ferenc, Hans-Georg Olbrich, Jörg Hausleiter, Gert Richardt, Marcus Hennersdorf, Klaus Empen, Georg Fuernau, Steffen Desch, Ingo Eitel, Rainer Hambrecht, Jörg Fuhrmann, Michael Böhm, Henning Ebelt, Steffen Schneider, Gerhard Schuler, Karl Werdan
Journal: New England Journal of Medicine (2012)

In current international guidelines, intraaortic balloon counterpulsation is considered to be a class I treatment for cardiogenic shock complicating acute myocardial infarction. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials.
Management of severe malaria in children: proposed guidelines for the United Kingdom
Authors: Kathryn Maitland, Simon Nadel, Andrew J Pollard, Thomas N Williams, Charles R J C Newton, Michael Levin
Journal: BMJ (2005)

Malaria is the most important vector borne disease worldwide. Globally it results in an estimated 400 million infections and more than 1 million deaths each year. Although malaria is a rare cause of hospital admission in the United Kingdom, it constitutes a substantial health threat for people travelling in endemic areas. The incidence of imported malaria is rising throughout much of the developed world, largely because of a global increase in long distance travel, immigration, and the resurgence of malaria in many tropical countries. Moreover, although Plasmodium vivax was once the most common form of imported malaria, it has since been superseded by P falciparum—the only form of malaria that can be lethal—which now accounts for some 80% of reported cases. Around 15% of episodes of malaria occur in children aged 15 years or younger. Most of those affected are UK residents of African ethnicity who have recently visited family in endemic areas but have not taken preventive measures. Nevertheless, even strict compliance with preventive measures is never 100% effective, as resistance to available chemoprophylactic agents is increasing in many parts of the world.  Although most cases of P falciparum malaria in patients presenting to health services in the UK are uncomplicated, up to 10% become severe and life threatening malaria, principally because of delays in diagnosis and inadequate treatment. In uncomplicated disease, the clinical features of malaria are similar in children and adults, but in severe disease, the clinical spectrum, complications, and management differ and merit the development of separate guidelines for children. We therefore propose the following guidelines for the assessment and emergency management of children with imported malaria.
20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease
Authors: Frank Park, William E. Sweeney, Guangfu Jia, Richard J. Roman, Ellis D. Avner
Journal: Journal of the American Society of Nephrology (2008)

Polycystic kidney diseases are characterized by abnormal proliferation of renal epithelial cells. In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily administration of HET-0016, an inhibitor of 20-HETE synthesis, significantly reduced kidney size by half in the BPK mouse model of autosomal recessive polycystic kidney disease. In addition, compared with untreated BPK mice, this treatment significantly reduced collecting tubule cystic indices and approximately doubled survival. For evaluation of the role of 20-HETE as a mediator of epithelial cell proliferation, principal cells isolated from cystic BPK and noncystic Balb/c mice were genetically modified using lentiviral vectors. Noncystic Balb/c cells overproducing Cyp4a12 exhibited a four- to five-fold increase in cell proliferation compared with control Balb/c cells, and this increase was completely abolished when 20-HETE synthesis was inhibited; therefore, this study suggests that 20-HETE mediates proliferation of epithelial cells in the formation of renal cysts.
Frequent Inactivation of <i>RAMP2, EFEMP1</i> and <i>Dutt1</i> in Lung Cancer by Promoter Hypermethylation
Authors: Wen Yue, Sanja Dacic, Quanhong Sun, Rodney Landreneau, Mingzhou Guo, Wei Zhou, Jill M. Siegfried, Jian Yu, Lin Zhang
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The goal of this study is to identify novel genes frequently silenced by promoter hypermethylation in lung cancer. Experimental Designs: Bioinformatic analysis was done to identify candidate genes significantly down-regulated in lung cancer. The effects of DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine on the expression of the candidate genes were determined. Methylated CpG sites in the promoters of the candidate genes were identified using bisulfite DNA sequencing. Methylation-specific PCR was developed and used to analyze DNA methylation in cell lines and clinical specimen. Pathologic and functional analyses were done to study the role of one candidate gene, receptor activity-modifying protein 2 (RAMP2), in suppressing lung cancer cell growth. Results: Among 54 candidate genes down-regulated in lung cancer, 31 were found to contain CpG islands in their promoters. Six of these 31 genes could be reactivated by 5-aza-2′-deoxycytidine in at least four of six lung cancer cell lines analyzed. Promoter hypermethylation of RAMP2, epidermal growth factor–containing fibulin-like extracellular matrix protein 1, and deleted in U Twenty Twenty cells was detected in 36% to 77% of 22 lung cancer cell lines and in 38% to 50% of 32 primary lung tumors, whereas hypermethylathion of these genes was rarely found in the matched normal samples. The methylation frequencies of these genes in lung cancer were similar to those of commonly used methylation markers, such as RAS association domain family protein 1A, p16, and methylguanine-DNA methyltransferase. Immunohistochemistry showed that RAMP2 was down-regulated in a majority of lung tumors, and RAMP2 down-regulation was correlated with high tumor grade. Ectopic expression of RAMP2 inhibited lung cancer cell growth and caused apoptotic cell death. Knockdown of RAMP2 by RNA interference stimulated cell proliferation. Conclusions: Studying the newly identified genes may provide new insight into lung tumorigenesis. These genes might be useful as molecular markers of lung cancer.
Diffuse large B-cell lymphoma with primary retroperitoneal presentation: Clinico-pathologic study of nine cases
Authors: S.A. Piled, P.L. Zinzani, S. Ascani, G. Fraternali Orcioni, B. Gamberi, M. Piccioli, E. Sabattini, S. Poggi, P.P. Piccaluga, B. Falini
Journal: Annals of Oncology (2001)
Human Splicing Factor SPF45 (<i>RBM17</i>) Confers Broad Multidrug Resistance to Anticancer Drugs When Overexpressed— a Phenotype Partially Reversed By Selective Estrogen Receptor Modulators
Authors: William L. Perry, Robert L. Shepard, Janardhan Sampath, Benjamin Yaden, William W. Chin, Philip W. Iversen, Shengfang Jin, Andrea Lesoon, Kathryn A. O'Brien, Victoria L. Peek, Mark Rolfe, Andrew Shyjan, Michelle Tighe, Mark Williamson, Venkatesh Krishnan, Robert E. Moore, Anne H. Dantzig
Journal: Cancer Research (2005)

The splicing factor SPF45 (RBM17) is frequently overexpressed in many solid tumors, and stable expression in HeLa cells confers resistance to doxorubicin and vincristine. In this study, we characterized stable transfectants of A2780 ovarian carcinoma cells. In a 3-day cytotoxicity assay, human SPF45 overexpression conferred 3- to 21-fold resistance to carboplatin, vinorelbine, doxorubicin, etoposide, mitoxantrone, and vincristine. In addition, resistance to gemcitabine and pemetrexed was observed at the highest drug concentrations tested. Knockdown of SPF45 in parental A2780 cells using a hammerhead ribozyme sensitized A2780 cells to etoposide by approximately 5-fold relative to a catalytically inactive ribozyme control and untransfected cells, suggesting a role for SPF45 in intrinsic resistance to some drugs. A2780-SPF45 cells accumulated similar levels of doxorubicin as vector-transfected and parental A2780 cells, indicating that drug resistance is not due to differences in drug accumulation. Efforts to identify small molecules that could block SPF45-mediated drug resistance revealed that the selective estrogen receptor (ER) modulators tamoxifen and LY117018 (a raloxifene analogue) partially reversed SPF45-mediated drug resistance to mitoxantrone in A2780-SPF45 cells from 21-fold to 8- and 5-fold, respectively, but did not significantly affect the mitoxantrone sensitivity of vector control cells. Quantitative PCR showed that ERbeta but not ERalpha was expressed in A2780 transfectants. Coimmunoprecipitation experiments suggest that SPF45 and ERbeta physically interact in vivo. Thus, SPF45-mediated drug resistance in A2780 cells may result in part from effects of SPF45 on the transcription or alternate splicing of ERbeta-regulated genes.
Etoposide Prevents Apoptosis in Mouse Liver With D–Galactosamine/Lipopolysaccharide–Induced Fulminant Hepatic Failure Resulting in Reduction of Lethality
Authors: Tetsufumi Nakama, Shuichi Hirono, Akihiro Moriuchi, Satoru Hasuike, Kenji Nagata, Takeshi Hori, Akio Ido, Katsuhiro Hayashi, Hirohito Tsubouchi
Journal: Hepatology (2001)

d–Galactosamine (GalN)/lipopolysaccharide (LPS)–induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor α (TNF–α) plays a pivotal role. We examined the effects of etoposide on GalN/LPS–induced fulminant hepatic failure. Mice were given an intraperitoneal dose of GalN (800 μg/g body weight)/LPS (100 ng/g body weight) with and without intraperitoneal etoposide (10 μg/g body weight) treatment. Liver injury was assessed biochemically and histologically. TNF–α levels in the serum, and apoptosis of hepatocytes and CPP32/caspase–3 in the liver, were determined. GalN/LPS treatment caused lethal liver injury in 87% of animals (13 of 15). The effect was associated with significant increases in TNF–α and alanine transaminase (ALT) levels in serum, the number of apoptotic hepatocytes, CPP32/caspase–3 activity, and TNF receptor 1 (TNFR1) mRNA expression in the liver. Etoposide (10 μg/g body weight) was given 3 times (at 50, 26, and 4 hours before GalN/LPS administration). Treatment of GalN/LPS–treated mice with etoposide reduced apoptosis of hepatocytes, resulting in reduction of lethality (13% [2 of 15]), while another topoisomerase II inhibitor, IRCF–193, showed no significant effect. The antilethal effect of etoposide was also confirmed in GalN/TNF–α-induced fulminant hepatic failure. Etoposide treatment reduced CPP32/caspase–3 activity in the liver, although it did not alter the serum TNF–α levels or hepatic TNFR1 mRNA expressions. In addition, etoposide treatment enhanced the mRNA and protein expression of Bcl–xL, an antiapoptotic molecule in the liver. The present findings suggest that etoposide prevents endotoxin–induced lethal liver injury by up–regulation of Bcl–xL, and that etoposide could be useful for the treatment of TNF–α-mediated liver diseases.
Skin nodules in palmar fasciitis and polyarthritis associated with carcinoma
Authors: N. Ch. Kyriazis
Journal: British Journal of Dermatology (1995)

Journal Article Skin nodules in palmar fasciitis and polyarthritis associated with carcinoma Get access N. Ch. Kyriazis N. Ch. Kyriazis Department of Rheumatology, ‘Asklepieio of Voula’ Hospital, 1 King Paul Street, 16673 Voula, Athens, Greece Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 2, 1 August 1995, Page 341, https://doi.org/10.1111/j.1365-2133.1995.tb02653.x Published: 01 August 1995
Propranolol treatment externalizes beta-adrenergic receptors in guinea pig myocardium and prevents further externalization by ischemia.
Authors: A S Maisel, H J Motulsky, P A Insel
Journal: Circulation Research (1987)

Purified sarcolemmal and light vesicle (intracellular) fractions of beta-adrenergic receptors were used to examine the effects of propranolol on receptor translocation in guinea pig heart. Guinea pigs were given propranolol (0.15 mg/kg/hr) via minipumps for 7 days and either killed or made ischemic for 1 hour via a coronary ligature. Propranolol treatment led to an externalization of beta-receptors from light vesicle to sarcolemmal fractions. This externalization increased the number of surface beta-adrenergic receptors that were functional, as assessed by isoproterenol-stimulated adenylate cyclase activity. After chronic propranolol treatment, ischemia did not further alter receptor distribution. These results suggest that externalization of beta-adrenergic receptors from a light vesicle fraction to the sarcolemma contributes to up-regulation of beta-receptors that occur in response to both propranolol treatment and ischemia. Because propranolol-treated animals show blunting in externalization after myocardial ischemia, propranolol treatment and myocardial ischemia appear to access the same pool of intracellular beta-adrenergic receptors. Depletion of this pool of receptors along with receptor blockade may thus contribute to the mechanism by which the drug is efficacious in preventing some adverse effects of ischemia.
Cdk2 Deficiency Decreases ras/CDK4-Dependent Malignant Progression, but Not myc-Induced Tumorigenesis
Authors: Everardo Macias, Yongbaek Kim, Paula L. Miliani de Marval, Andres Klein-Szanto, Marcelo L. Rodriguez-Puebla
Journal: Cancer Research (2007)

Abstract We have previously shown that forced expression of CDK4 in mouse skin (K5CDK4 mice) results in increased susceptibility to squamous cell carcinoma (SCC) development in a chemical carcinogenesis protocol. This protocol induces skin papilloma development, causing a selection of cells bearing activating Ha-ras mutations. We have also shown that myc-induced epidermal proliferation and oral tumorigenesis (K5Myc mice) depends on CDK4 expression. Biochemical analysis of K5CDK4 and K5Myc epidermis as well as skin tumors showed that keratinocyte proliferation is mediated by CDK4 sequestration of p27Kip1 and p21Cip1, and activation of CDK2. Here, we studied the role of CDK2 in epithelial tumorigenesis. In normal skin, loss of CDK2 rescues CDK4-induced, but not myc-induced epidermal hyperproliferation. Ablation of CDK2 in K5CDK4 mice results in decreased incidences and multiplicity of skin tumors as well as malignant progression to SCC. Histopathologic analysis showed that K5CDK4 tumors are drastically more aggressive than K5CDK4/CDK2−/− tumors. On the other hand, we show that CDK2 is dispensable for myc-induced tumorigenesis. In contrast to our previous report of K5Myc/CDK4−/−, K5Myc/CDK2−/− mice developed oral tumors with the same frequency as K5Myc mice. Overall, we have established that ras-induced tumors are more susceptible to CDK2 ablation than myc-induced tumors, suggesting that the efficacy of targeting CDK2 in tumor development and malignant progression is dependent on the oncogenic pathway involved. [Cancer Res 2007;67(20):9713–20]
A 6-Month, Randomized, Double-Masked, Placebo-Controlled Study Evaluating the Effects of the Protein Kinase C-β Inhibitor Ruboxistaurin on Skin Microvascular Blood Flow and Other Measures of Diabetic Peripheral Neuropathy
Authors: Carolina M. Casellini, Patricia M. Barlow, Amanda L. Rice, Melissa Casey, Kathryn Simmons, Gary Pittenger, Edward J. Bastyr, Anne M. Wolka, Aaron I. Vinik
Journal: Diabetes Care (2007)

OBJECTIVE—Diabetes leads to protein kinase C (PKC)-β overactivation and microvascular dysfunction, possibly resulting in disordered skin microvascular blood flow (SkBF) and other changes observed in diabetic peripheral neuropathy (DPN) patients. We investigate the effects of the isoform-selective PKC-β inhibitor ruboxistaurin mesylate on neurovascular function and other measures of DPN. RESEARCH DESIGN AND METHODS—Endothelium-dependent and C fiber–mediated SkBF, sensory symptoms, neurological deficits, nerve fiber morphometry, quantitative sensory and autonomic function testing, nerve conduction studies, quality of life (using the Norfolk Quality-of-Life Questionnaire for Diabetic Neuropathy [QOL-DN]), and adverse events were evaluated for 20 placebo- and 20 ruboxistaurin-treated (32 mg/day) DPN patients (aged ≥18 years; with type 1 or type 2 diabetes and A1C ≤11%) during a randomized, double-masked, single-site, 6-month study. RESULTS—Endothelium-dependent (+78.2%, P &amp;lt; 0.03) and C fiber–mediated (+56.4%, P &amp;lt; 0.03) SkBF at the distal calf increased from baseline to end point. Significant improvements from baseline within the ruboxistaurin group were also observed for the Neuropathy Total Symptom Score-6 (NTSS-6) (3 months −48.3%, P = 0.01; end point −66.0%, P &amp;lt; 0.0006) and the Norfolk QOL-DN symptom subscore and total score (end point −41.2%, P = 0.01, and −41.0, P = 0.04, respectively). Between-group differences in baseline–to–end point change were observed for NTSS-6 total score (placebo −13.1%; ruboxistaurin −66.0%, P &amp;lt; 0.03) and the Norfolk QOL-DN symptom subscore (placebo −4.0%; ruboxistaurin −41.2%, P = 0.041). No significant ruboxistaurin effects were demonstrated for the remaining efficacy measures. Adverse events were consistent with those observed in previous ruboxistaurin studies. CONCLUSIONS—In this cohort of DPN patients, ruboxistaurin enhanced SkBF at the distal calf, reduced sensory symptoms (NTSS-6), improved measures of Norfolk QOL-DN, and was well tolerated.