tbuckley/cabot-search huggingface dataset:
O-Glycosylated IgA Rheumatoid Factor Induces IgA Deposits and Glomerulonephritis
Authors: Masako Otani, Junichiro Nakata, Masao Kihara, Valérie Leroy, Solange Moll, Yoshinao Wada, Shozo Izui
Journal: Journal of the American Society of Nephrology (2011)

Structural aberrations of O-linked glycans present in the IgA1 hinge region are associated with IgA nephropathy, but their contribution to its pathogenesis remains incompletely understood. In this study, mice implanted with hybridoma secreting 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA rheumatoid factor bearing the same IgA allotype, developed mesangial deposits consisting of IgA, IgG2a, and C3. Studies in immunoglobulin- and C3-deficient mice revealed that the development of these glomerular lesions required the formation of IgA-IgG2a immune complexes and subsequent activation of complement. The proportion of polymeric and monomeric forms, the IgG2a-binding affinity, and the serum levels of IgA-IgG2a immune complexes were similar between 6-19 IgA- and 46-42 IgA-injected mice. In contrast, the analysis of oligosaccharide structures revealed highly galactosylated O-linked glycans in the hinge region of 6-19 IgA and poorly O-glycosylated in the hinge region of 46-42 IgA. Furthermore, the structure of N-linked glycans in the CH1 domain was the complex type in 6-19 IgA and the hybrid type in 46-42 IgA. In summary, this study demonstrates the presence of O-linked glycans in the hinge region of mouse IgA and suggests that 6-19 IgA rheumatoid factor-induced GN could serve as an experimental model for IgA nephropathy.
55 SELECTIVE ACTIVATION OF INTRAHEPATIC IMMUNITY WITH TLR8 AGONIST: A POTENT THERAPEUTIC STRATEGY TO BOOST ANTIVIRAL IMMUNITY IN HUMAN LIVER
Authors: J. Jo, X.-Z. Tang, A.T. Tan, E. Sandalova, A. Chia, K.C. Tan, K.H. Lee, A.J. Gehring, A. Bertoletti
Journal: Journal of Hepatology (2013)
Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells
Authors: Keli L. Hippen, Paul Harker-Murray, Stephen B. Porter, Sarah C. Merkel, Aryel Londer, Dawn K. Taylor, Megan Bina, Angela Panoskaltsis-Mortari, Pablo Rubinstein, Nico Van Rooijen, Tatiana N. Golovina, Megan M. Suhoski, Jeffrey S. Miller, John E. Wagner, Carl H. June, James L. Riley, Bruce R. Blazar
Journal: Blood (2008)
Coronary blood flow and myocardial metabolism in acute experimental anaemia
Authors: J. F. MURRAY, E. RAPAPORT
Journal: Cardiovascular Research (1972)

Journal Article Coronary blood flow and myocardial metabolism in acute experimental anaemia Get access JOHN F. MURRAY, JOHN F. MURRAY From the Medical Service, San Francisco General Hospital, and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar ELLIOT RAPAPORT ELLIOT RAPAPORT From the Medical Service, San Francisco General Hospital, and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 4, July 1972, Pages 360–367, https://doi.org/10.1093/cvr/6.4.360 Published: 01 July 1972
Synergistic Growth Inhibition by 9-<i>cis</i>-Retinoic Acid Plus Trastuzumab in Human Hepatocellular Carcinoma Cells
Authors: Hideharu Tatebe, Masahito Shimizu, Yohei Shirakami, Hisashi Tsurumi, Hisataka Moriwaki
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A malfunction of retinoid X receptor-α (RXRα) due to phosphorylation by the Ras/mitogen-activated protein kinase signaling pathway is associated with the development of hepatocellular carcinoma (HCC). The humanized anti-HER2 monoclonal antibody trastuzumab inhibits the activation of HER2 and its multiple downstream signaling pathways, including the Ras/mitogen-activated protein kinase pathway. In this study, the effects of phosphorylation of RXRα on the ability of RXRα ligand 9-cis-retinoic acid (9cRA) and trastuzumab to inhibit growth of HCC cells was examined. Experimental Design: The effects of a combination of 9cRA plus trastuzumab on the inhibition of cell growth in HLF human HCC cells which express constitutive activation of HER2 protein were examined. Results: The combination of 9cRA plus trastuzumab synergistically inhibited the growth of HLF cells without affecting the growth of Hc normal human hepatocytes. Combined treatment with these agents acted synergistically to induce apoptosis in HLF cells. The treatment of HLF cells with trastuzumab alone inhibited the phosphorylation of HER2, RXRα, ERK, Akt, and Stat3 proteins and these effects were enhanced when the cells were cotreated with 9cRA. Reporter assays indicated that the combination of 9cRA plus trastuzumab markedly increased both the retinoic acid responsive element and retinoid X responsive element promoter activities in HLF cells. Conclusion: 9cRA and trastuzumab cooperatively inhibit the activation of HER2 and its downstream signaling pathways, subsequently inhibiting the phosphorylation of RXRα and the growth of HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC.
Vascular Responses at Proximal and Distal Edges of Paclitaxel-Eluting Stents
Authors: Patrick W. Serruys, Muzaffer Degertekin, Kengo Tanabe, Mary E. Russell, Giulio Guagliumi, John Webb, Jaap Hamburger, Wolfgang Rutsch, Christoph Kaiser, Robert Whitbourn, Edoardo Camenzind, Ian Meredith, François Reeves, Christoph Nienaber, Edouard Benit, Clemens Disco, Jörg Koglin, Antonio Colombo
Journal: Circulation (2004)

On the basis of brachytherapy experience, edge stenosis has been raised as a potential limitation for drug-eluting stents. We used serial intravascular ultrasound (IVUS) to prospectively analyze vessel responses in adjacent reference segments after implantation of polymer-controlled paclitaxel-eluting stents.TAXUS II was a randomized, double-blind trial with 2 consecutive patient cohorts that compared slow-release (SR) and moderate-release (MR) paclitaxel-eluting stents with control bare metal stents (BMS). By protocol, all patients had postprocedure and 6-month follow-up IVUS. Quantitative IVUS analysis was performed by an independent core laboratory, blinded to treatment allocation, in 5-mm vessel segments immediately proximal and distal to the stent. Serial IVUS was available for 106 SR, 107 MR, and 214 BMS patients. For all 3 groups, a significant decrease in proximal-edge lumen area was observed at 6 months. The decrease was comparable (by ANOVA, P=0.194) for patients in the SR (-0.54+/-2.1 mm2) and MR (-0.88+/-1.9 mm2) groups compared with the BMS (-1.02+/-1.9 mm2) group. For the distal edge, a significant decrease in lumen area was only observed with BMS (-0.91+/-2.0 mm2, P<0.0001); this decrease was significantly attenuated with SR (0.08+/-2.0 mm2) and MR (-0.19+/-1.7 mm2) stents (P<0.0001 by ANOVA). Negative vessel remodeling was observed at the proximal (-0.48+/-2.2 mm2, P=0.011) but not the distal edges of BMS and at neither edge of SR or MR stents.The marked reduction in in-stent restenosis with SR or MR stents is not associated with increased edge stenosis at 6-month follow-up IVUS. In fact, compared with BMS, there is instead a significant reduction in late lumen loss at the distal edge with TAXUS stents.
Systematic Review: Comparative Effectiveness and Harms of Combination Therapy and Monotherapy for Dyslipidemia
Authors: Mukul Sharma, Mohammed T. Ansari, Ahmed M. Abou-Setta, Karla Soares-Weiser, Teik Chye Ooi, Margaret Sears, Fatemeh Yazdi, Alexander Tsertsvadze, David Moher
Journal: Annals of Internal Medicine (2009)

Statin therapy effectively prevents vascular disease, but treatment targets are often not achieved.To compare the benefits and harms of high-dose statin monotherapy with those of combination therapy in adults at high risk for coronary disease.English-language records from MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and the Cochrane Library (third quarter of 2008).A reviewer screened records, and a second reviewer verified selection of randomized, controlled trials in adult patients that compared combinations of statins and bile-acid sequestrants, fibrates, ezetimibe, niacin, or omega-3 fatty acids with statin monotherapy, as well as nonrandomized comparative studies that were longer than 24 weeks and reported clinical and harms outcomes.Data were abstracted for studies by using standardized forms, and study quality was rated with a standardized scale and strength of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation approach.102 studies met eligibility criteria. The main analysis compared combination therapy with high-dose statin monotherapy in high-risk patients. Very-low-strength evidence showed that statin-ezetimibe (2 trials; n = 439) and statin-fibrate (1 trial; n = 166) combinations did not reduce mortality more than high-dose statin monotherapy. No trials compared the effect of combination therapy versus high-dose statin monotherapy on the incidence of myocardial infarction, stroke, or revascularization procedures. Two statin-ezetimibe trials (n = 295) demonstrated higher low-density lipoprotein cholesterol goal attainment with combination therapy (odds ratio, 7.21 [95% CI, 4.30 to 12.08]). Trials in lower-risk patients did not show a difference in mortality.Studies were generally short, focused on surrogate outcomes, and were heterogeneous in the sample's risk for coronary disease. Few studies examined treatment combinations other than statin-ezetimibe.Limited evidence suggests that combinations of lipid-lowering agents do not improve clinical outcomes more than high-dose statin monotherapy. Very-low-quality evidence favors statin-ezetimibe treatment for attainment of low-density lipoprotein cholesterol goals.Agency for Healthcare Research and Quality.
Active transendothelial transport of albumin. Interstitium to lumen.
Authors: D M Shasby, S S Shasby
Journal: Circulation Research (1985)

Cultured porcine pulmonary artery endothelial monolayers actively transport albumin from interstitium to lumen. The active process favors interstitial to luminal transport by a factor of 10 even in the face of a 2:1 luminal:interstitial albumin gradient. The active process is abolished by treatment with 1 mM sodium cyanide. Dextran is not actively transported. This process could be important in determining transvascular fluid balance and transfer of macromolecules across the endothelium.
Host Alloreactive Memory T Cells Influence Tolerance to Kidney Allografts in Nonhuman Primates
Authors: Ognjenka Nadazdin, Svjetlan Boskovic, Toru Murakami, Georges Tocco, Rex-Neal Smith, Robert B. Colvin, David H. Sachs, James Allan, Joren C. Madsen, Tatsuo Kawai, A. Benedict Cosimi, Gilles Benichou
Journal: Science Translational Medicine (2011)

Only nonhuman primates with low frequencies of donor-specific memory T cells develop tolerance and accept allogeneic kidney transplants.
State of Disparities in Cardiovascular Health in the United States
Authors: George A. Mensah, Ali H. Mokdad, Earl S. Ford, Kurt J. Greenlund, Janet B. Croft
Journal: Circulation (2005)

Reducing health disparities remains a major public health challenge in the United States. Having timely access to current data on disparities is important for policy and program development. Accordingly, we assessed the current magnitude of disparities in cardiovascular disease (CVD) and its risk factors in the United States.Using national surveys, we determined CVD and risk factor prevalence and indexes of morbidity, mortality, and overall quality of life in adults > or =18 years of age by race/ethnicity, sex, education level, socioeconomic status, and geographic location. Disparities were common in all risk factors examined. In men, the highest prevalence of obesity (29.2%) was found in Mexican Americans who had completed a high school education. Black women with or without a high school education had a high prevalence of obesity (47.3%). Hypertension prevalence was high among blacks (39.8%) regardless of sex or educational status. Hypercholesterolemia was high among white and Mexican American men and white women in both groups of educational status. Ischemic heart disease and stroke were inversely related to education, income, and poverty status. Hospitalization was greater in men for total heart disease and acute myocardial infarction but greater in women for congestive heart failure and stroke. Among Medicare enrollees, congestive heart failure hospitalization was higher in blacks, Hispanics, and American Indians/Alaska Natives than among whites, and stroke hospitalization was highest in blacks. Hospitalizations for congestive heart failure and stroke were highest in the southeastern United States. Life expectancy remains higher in women than men and higher in whites than blacks by approximately 5 years. CVD mortality at all ages tended to be highest in blacks.Disparities in CVD and related risk factors remain pervasive. The data presented here can be invaluable for policy development and in the planning, implementation, and evaluation of interventions designed to eliminate health disparities.
Hepatitis C infection, antiviral treatment and mental health: A European expert consensus statement
Authors: Martin Schaefer, Lucile Capuron, Astrid Friebe, Crisanto Diez-Quevedo, Geert Robaeys, Sergio Neri, Graham R. Foster, Achim Kautz, Daniel Forton, Carmine M. Pariante
Journal: Journal of Hepatology (2012)
Phase II Trial of Cetuximab, Gemcitabine, and Oxaliplatin Followed by Chemoradiation With Cetuximab for Locally Advanced (T4) Pancreatic Adenocarcinoma: Correlation of <i>Smad4(Dpc4)</i> Immunostaining With Pattern of Disease Progression
Authors: Christopher H. Crane, Gauri R. Varadhachary, John S. Yordy, Gregg A. Staerkel, Milind M. Javle, Howard Safran, Waqar Haque, Bridgett D. Hobbs, Sunil Krishnan, Jason B. Fleming, Prajnan Das, Jeffrey E. Lee, James L. Abbruzzese, Robert A. Wolff
Journal: Journal of Clinical Oncology (2011)

Purpose This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Patients and Methods Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m 2 ) and oxaliplatin (100 mg/m 2 ) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m 2 twice daily on radiation treatment days). Cetuximab (500 mg/m 2 ) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Results Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). Conclusion This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate &gt; 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.
Vessel-Specific Toll-Like Receptor Profiles in Human Medium and Large Arteries
Authors: Olga Pryshchep, Wei Ma-Krupa, Brian R. Younge, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Circulation (2008)

Background— Inflammatory vasculopathies, ranging from the vasculitides (Takayasu arteritis, giant cell arteritis, and polyarteritis nodosa) to atherosclerosis, display remarkable target tissue tropisms for selected vascular beds. Molecular mechanisms directing wall inflammation to restricted anatomic sites within the vascular tree are not understood. We have examined the ability of 6 different human macrovessels (aorta and subclavian, carotid, mesenteric, iliac, and temporal arteries) to initiate innate and adaptive immune responses by comparing pathogen-sensing and T-cell–stimulatory capacities. Methods and Results— Gene expression analysis for pathogen-sensing Toll-like receptors (TLRs) 1 to 9 showed vessel-specific profiles, with TLR2 and TLR4 ubiquitously present, TLR7 and TLR9 infrequent, and TLR1, TLR3, TLR5, TLR6, and TLR8 expressed in selective patterns. Experiments with vessel walls stripped of the intimal or adventitial layer identified dendritic cells at the media-adventitia junction as the dominant pathogen sensors. In human artery–severe combined immunodeficiency (SCID) mouse chimeras, adoptively transferred human T cells initiated vessel wall inflammation if wall-embedded dendritic cells were conditioned with TLR ligands. Wall-infiltrating T cells displayed vessel-specific activation profiles with differential production of CD40L, lymphotoxin-α, and interferon-γ. Vascular bed–specific TLR fingerprints were functionally relevant, as exemplified by differential responsiveness of iliac and subclavian vessels to TLR5 but not TLR4 ligands. Conclusions— Populated by indigenous dendritic cells, medium and large human arteries have immune-sensing and T-cell–stimulatory functions. Each vessel in the macrovascular tree exhibits a distinct TLR profile and supports selective T-cell responses, imposing vessel-specific risk for inflammatory vasculopathies.
Therapeutic Targeting of PELP1 Prevents Ovarian Cancer Growth and Metastasis
Authors: Dimple Chakravarty, Sudipa Saha Roy, Challa Ram Babu, Rajasekhar Dandamudi, Tyler J. Curiel, Pablo Vivas-Mejia, Gabriel Lopez-Berestein, Anil K. Sood, Ratna K. Vadlamudi
Journal: Clinical Cancer Research (2011)

Ovarian cancer remains a major threat to women's health, partly due to difficulty in early diagnosis and development of metastases. A critical need exists to identify novel targets that curb the progression and metastasis of ovarian cancer. In this study, we examined whether the nuclear receptor coregulator PELP1 (proline-, glutamic acid-, leucine-rich protein-1) contributes to progression and metastatic potential of ovarian cancer cells and determined whether blocking of the PELP1 signaling axis had a therapeutic effect.Ovarian cancer cells stably expressing PELP1-shRNA (short hairpin RNA) were established. Fluorescent microscopy, Boyden chamber, invasion assays, wound healing, and zymography assays were performed to examine the role of PELP1 in metastasis. Expression analysis of the model cells was conducted using tumor metastasis microarray to identify PELP1 Target genes. Therapeutic potential of PELP1-siRNA in vivo was determined using a nanoliposomal formulation of PELP1-siRNA-DOPC (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) administered systemically in a xenograft model.PELP1 knockdown caused cytoskeletal defects and significantly affected the migratory potential of ovarian cancer cells. Microarray analysis revealed that PELP1 affected the expression of selective genes involved in metastasis including Myc, MTA1, MMP2, and MMP9. Zymography analysis confirmed that PELP1 knockdown caused a decrease in the activation of matrix metalloproteases (MMP) 2 and MMP9. Compared with control siRNA-DOPC-treated mice, animals injected with PELP1-siRNA-DOPC had 54% fewer metastatic tumor nodules, exhibited a 51% reduction in tumor growth and an 84% reduction in ascites volume.The results suggest that PELP1 signaling axis is a potential druggable target and liposomal PELP1-siRNA-DOPC could be used as a novel drug to prevent or treat ovarian metastasis.
The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology
Authors: Gerard Manning, David S Reiner, Tineke Lauwaet, Michael Dacre, Alias Smith, Yufeng Zhai, Staffan Svard, Frances D Gillin
Journal: Genome biology (2011)

The major human intestinal pathogen Giardia lamblia is a very early branching eukaryote with a minimal genome of broad evolutionary and biological interest.To explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm.The reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton.
Failure of Vaccinated Children to Transmit Measles
Authors: A. David Brandling-Bennett
Journal: JAMA (1973)

During an epidemic of measles in Des Moines County, Iowa, 72% of the 541 cases involved school-age children. Sixty-three percent of children aged 1 to 9 years in the county had been vaccinated previously. A survey for cases of measles in preschool siblings of school age children suggested that previously vaccinated children, in an epidemic, do not transmit measles to their susceptible siblings.