tbuckley/cabot-search huggingface dataset:
Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis
Authors: Anna Bertram, Svjetlana Lovric, Alissa Engel, Michaela Beese, Kristin Wyss, Barbara Hertel, Joon-Keun Park, Jan U. Becker, Johanna Kegel, Hermann Haller, Marion Haubitz, Torsten Kirsch
Journal: Journal of the American Society of Nephrology (2015)

ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease.
Multicenter Clinical Trial of Bortezomib in Relapsed/Refractory Waldenstrom's Macroglobulinemia: Results of WMCTG Trial 03-248
Authors: Steven P. Treon, Zachary R. Hunter, Jeffrey Matous, Robin M. Joyce, Brian Mannion, Ranjana Advani, David Cook, Joseph Songer, John Hill, Bruce R. Kaden, David Sharon, Ronald Steiss, Xavier Leleu, Andrew R. Branagan, Ashraf Badros
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Waldenstrom's macroglobulinemia (WM) is a B-cell disorder. Despite advances in the therapy, WM remains incurable. As such, novel therapeutic agents are needed for the treatment of WM. Experimental Design: In this multicenter study, 27 patients with WM received up to eight cycles of bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11. All but one patient had relapsed/or refractory disease. Results: Following therapy, median serum IgM levels declined from 4,660 to 2,092 mg/dL (P &amp;lt; 0.0001). The overall response rate was 85%, with 10 and 13 patients achieving minor and major responses, respectively. Responses were prompt and occurred at median of 1.4 months. The median time to progression for all responding patients was 7.9 (range, 3-21.4+) months. The most common grade III/IV toxicities occurring in ≥5% of patients were sensory neuropathies (22.2%), leukopenia (18.5%), neutropenia (14.8%), dizziness (11.1%), and thrombocytopenia (7.4%). Sensory neuropathies resolved or improved in nearly all patients following cessation of therapy. Conclusions: The results of these studies show that bortezomib is an active agent in relapsed and refractory WM.
Pathophysiological Levels of Soluble P-Selectin Mediate Adhesion of Leukocytes to the Endothelium Through Mac-1 Activation
Authors: Kevin J. Woollard, Andreas Suhartoyo, Emma E. Harris, Steffen U. Eisenhardt, Shaun P. Jackson, Karlheinz Peter, Anthony M. Dart, Michael J. Hickey, Jaye P.F. Chin-Dusting
Journal: Circulation Research (2008)

Plasma soluble P-selectin (sP-selectin) levels are increased in pathologies associated with atherosclerosis, including peripheral arterial occlusive disease (PAOD). However, the role of sP-selectin in regulating leukocyte-endothelial adhesion is unclear. The aim of this study was to assess the ability of exogenous and endogenous sP-selectin to induce leukocyte responses that promote their adhesion to various forms of endothelium. In flow chamber assays, sP-selectin dose-dependently increased neutrophil adhesion to resting human iliac artery endothelial cells. Similarly, sP-selectin induced neutrophil adhesion to the endothelial surface of murine aortae and human radial venous segments in ex vivo flow chamber experiments. Using intravital microscopy to examine postcapillary venules in the mouse cremaster muscle, in vivo administration of sP-selectin was also found to significantly increase leukocyte rolling and adhesion in unstimulated postcapillary venules. Using a Mac-1-specific antibody and P-selectin knockout mouse, it was demonstrated that this finding was dependent on a contribution of Mac-1 to leukocyte rolling and endothelial P-selectin expression. This was confirmed in an ex vivo perfusion model using viable mouse aorta and human radial vessels. In contrast, with tumor necrosis factor-alpha-activated endothelial cells and intact endothelium, where neutrophil adhesion was already elevated, sP-selectin failed to further increase adhesion. Plasma samples from PAOD patients containing pathologically elevated concentrations of sP-selectin also increased neutrophil adhesion to the endothelium in a sP-selectin-dependent manner, as demonstrated by immunodepletion of sP-selectin. These studies demonstrate that raised plasma sP-selectin may influence the early progression of vascular disease by promoting leukocyte adhesion to the endothelium in PAOD, through Mac-1-mediated rolling and dependent on endothelial P-selectin expression.
The Effectiveness of β-Blockers After Myocardial Infarction in Patients With Type 2 Diabetes
Authors: Charlotte G. McDonald, Sumit R. Majumdar, Jeffrey L. Mahon, Jeffrey A. Johnson
Journal: Diabetes Care (2005)

Beta-blocker therapy has been proven to reduce mortality and reinfarction after myocardial infarction (MI), but the impact of beta-blockers on cardiac outcomes in patients with type 2 diabetes in routine practice is not clear. The purpose of this study was to determine the effectiveness of beta-blockers after MI in patients with type 2 diabetes.Using the Saskatchewan Health Databases, 12,272 patients with newly treated diabetes were identified between 1991 and 1996; 625 patients were subsequently admitted for MI. Beta-blocker exposure within 30 days of discharge was identified in 298 patients, and all were followed until death, coverage termination, or 31 December 1999. Multivariate proportional hazards models were used to assess differences in all-cause mortality, recurrent MI, and 30-day all-cause rehospitalization (the latter a proxy measure for drug safety).Patients were aged 69 +/- 11 years old, 66% were male, and mean follow-up was 2.7 +/- 2.1 years. Overall, beta-blockers were prescribed for 48% of patients. There were fewer deaths in the beta-blocker group versus control subjects (55 of 298 [18.5%] vs. 126 of 327 [38.5%], respectively, P < 0.001). However, beta-blockers were not associated with improved survival in multivariate analyses (hazard ratio [HR] 0.89 [95% CI 0.63-1.25]). There were no differences in rates of recurrent MI (adjusted HR 1.35 [0.93-1.95]) or rehospitalizations (adjusted odds ratio 1.40 [0.83-2.37]) between the groups.Beta-blocker therapy post-MI was not associated with reduced mortality or fewer recurrent events in people with type 2 diabetes in routine practice, although these medications were safe in this population.
Identifying the Basal Angiosperm Node in Chloroplast Genome Phylogenies: Sampling One's Way Out of the Felsenstein Zone
Authors: Jim Leebens-Mack, Linda A Raubeson, Liying Cui, Jennifer V Kuehl, Matthew H Fourcade, Timothy W Chumley, Jeffrey L Boore, Robert K Jansen, Claude W depamphilis
Journal: Molecular Biology and Evolution (2005)

While there has been strong support for Amborella and Nymphaeales (water lilies) as branching from basal-most nodes in the angiosperm phylogeny, this hypothesis has recently been challenged by phylogenetic analyses of 61 protein-coding genes extracted from the chloroplast genome sequences of Amborella, Nymphaea, and 12 other available land plant chloroplast genomes. These character-rich analyses placed the monocots, represented by three grasses (Poaceae), as sister to all other extant angiosperm lineages. We have extracted protein-coding regions from draft sequences for six additional chloroplast genomes to test whether this surprising result could be an artifact of long-branch attraction due to limited taxon sampling. The added taxa include three monocots (Acorus, Yucca, and Typha), a water lily (Nuphar), a ranunculid (Ranunculus), and a gymnosperm (Ginkgo). Phylogenetic analyses of the expanded DNA and protein data sets together with microstructural characters (indels) provided unambiguous support for Amborella and the Nymphaeales as branching from the basal-most nodes in the angiosperm phylogeny. However, their relative positions proved to be dependent on the method of analysis, with parsimony favoring Amborella as sister to all other angiosperms and maximum likelihood (ML) and neighbor-joining methods favoring an Amborella + Nymphaeales clade as sister. The ML phylogeny supported the later hypothesis, but the likelihood for the former hypothesis was not significantly different. Parametric bootstrap analysis, single-gene phylogenies, estimated divergence dates, and conflicting indel characters all help to illuminate the nature of the conflict in resolution of the most basal nodes in the angiosperm phylogeny. Molecular dating analyses provided median age estimates of 161 MYA for the most recent common ancestor (MRCA) of all extant angiosperms and 145 MYA for the MRCA of monocots, magnoliids, and eudicots. Whereas long sequences reduce variance in branch lengths and molecular dating estimates, the impact of improved taxon sampling on the rooting of the angiosperm phylogeny together with the results of parametric bootstrap analyses demonstrate how long-branch attraction might mislead genome-scale phylogenetic analyses.
Does pre-existing donor heart atherosclerosis lead to more transplant coronary artery disease? A prospective study using morphometric analysis of intracoronary ultrasound
Authors: Jay A. Johnson, Jon A. Kobashigawa, Lawrence Yeatman, Jeffrey G. Carr, Kevin D. Trosian, Alejandro Sabad, Lianne S. Wener, Davis Drinkwater, Hillei Laks
Journal: Journal of the American College of Cardiology (1996)
Flavokawain B, a kava chalcone, inhibits growth of human osteosarcoma cells through G2/M cell cycle arrest and apoptosis
Authors: Tao Ji, Carol Lin, Lauren S Krill, Ramez Eskander, Yi Guo, Xiaolin Zi, Bang H Hoang
Journal: Molecular Cancer (2013)

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Limited by the severe toxicity of conventional agents, the therapeutic bottleneck of osteosarcoma still remains unconquered. Flavokawain B (FKB), a kava extract, has been reported to have significant anti-tumor effects on several carcinoma cell lines both in vitro and in vivo. Its efficacy and low toxicity profile make FKB a promising agent for use as a novel chemotherapeutic agent.In the current study, we investigated the anti-proliferative and apoptotic effects of FKB against human osteosarcomas. Exposure of OS cells to FKB resulted in apoptosis, evidenced by loss of cell viability, morphological changes and the externalization of phosphatidylserine. Apoptosis induced by FKB resulted in activation of Caspase-3/7, -8 and -9 in OS cell lines, 143B and Saos-2. FKB also down-regulated inhibitory apoptotic markers, including Bcl-2 and Survivin and led to concomitant increases in apoptotic proteins, Bax, Puma and Fas. Therefore, the induction of apoptosis by FKB involved both extrinsic and intrinsic pathways. FKB also caused G2/M phase cell cycle arrest, which was observed through reductions in the levels of cyclin B1, cdc2 and cdc25c and increases in Myt1 levels. Furthermore, migration and invasion ability was decreased by FKB in a dose-dependent manner. The cytotoxicity profile showed FKB had significant lower side effects on bone marrow cells and small intestinal epithelial cells compared with Adriamycin.Taken together, our evidence of apoptosis and cell cycle arrest by FKB treatment with less toxicity than the standard treatments provides an innovative argument for the use of FKB as a chemotherapeutic and chemopreventive compound. In vivo experiments utilizing FKB to reduce tumorigenesis and metastatic potential will be crucial to further justify clinical application.
Evaluation of prospectively collected presenting signs/symptoms of biopsy-proven melanoma, basal cell carcinoma, squamous cell carcinoma, and seborrheic keratosis in an elderly male population
Authors: Sharone K. Askari, Sarah E. Schram, Rachel A. Wenner, Sacharitha Bowers, An Liu, Ann K. Bangerter, Erin M. Warshaw
Journal: Journal of the American Academy of Dermatology (2007)
BEHAVIORAL CHANGES DURING HYPOTHALAMIC OR LIMBIC STIMULATION IN THE MONKEY
Authors: LORNE D. PROCTOR, ROBERT D. KNIGHTON, JEROME LUKASZEWSKI, JOSE BEBIN
Journal: American Journal of Psychiatry (1960)

Stimulation of various areas of the limbic and hypothalamic regions in the Macaca mulatta resulted in a variety of responses. These responses were compared with those obtained on stimulating areas of the mid-brain reticular formation. It would appear that "overlapping" occurs as to the function of the limbic system, the mesencephalic reticular formation and the hypothalamus, in view of the similarity of behavior patterns elicited by stimulating some areas in these three different regions. The EEG patterns from the limbic, reticular (mesencephalic) and hypothalamic systems varied significantly so as to suggest that each system may function basically as an individual component system of the brain, probably influenced by ramifications one with the other. This EEG study is a preliminary investigation.
Systemic xanthohistiocytoma: a variant of xanthoma disseminatum?
Authors: None Ferrando, None Campo-Voegeli, None Soler-Carrillo, None MUNoz, None SolE, None Palou, None Conill, None Graus, None BombI, None Mascaro
Journal: British Journal of Dermatology (1998)

We present a 66-year-old man who had maculopapular pigmented lesions on the skin of the head, neck and trunk suggesting generalized eruptive histiocytoma (GEH). These lesions had a yellowish centre in a target-like pattern that has not been previously described. The patient suffered from diplopia and had a severe sensorimotor polyneuropathy causing progressive paresis of the limbs. The explorations performed disclosed the presence of specific xanthomatous infiltrates in the skin, lungs, respiratory tract, peripheral nerves and meninges, suggesting xanthoma disseminatum (XD) or juvenile xanthogranuloma. Multiple osteolytic lesions of large bones were also found. The infiltrate was CD68, MAC 387 and factor XIIIa positive and S-100 and CD1 negative. Some cells contained worm-like bodies visible by electron microscopy. Our patient presented clinical and immunohistochemical findings suggestive of GEH, juvenile xanthogranuloma or XD, supporting the idea of a wide spectrum of non-Langerhans cell histiocytosis. These specific target-like xanthomatous lesions seem to be unique for this new variant of XD.
CCL21 Chemokine Regulates Chemokine Receptor CCR7 Bearing Malignant Melanoma Cells
Authors: Hiroya Takeuchi, Akihide Fujimoto, Maki Tanaka, Tomoki Yamano, Eddy Hsueh, Dave S. B. Hoon
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The chemokine CC-ligand 21/secondary lymphoid tissue chemokine (CCL21/SLC) regulates the homing of naïve T cells and dendritic cells that express CC-chemokine receptor 7 (CCR7) from distant sites to lymphoid tissue such as lymph nodes. We hypothesized that CCL21/SLC regulates the migration of CCR7-bearing melanoma cells from a primary lesion to regional tumor-draining lymph nodes. Experimental Design: Quantitative real-time reverse transcriptase-PCR (qRT) assay and immunohistochemistry (IHC) were used to assess the level of CCR7 expression in melanoma cell lines and in primary and metastatic melanoma tumors. Cell migration assay using melanoma cell lines was performed under the induction of CCL21/SLC. The CCL21/SLC expression level in tumor-draining sentinel lymph nodes (SLNs) was assessed by both qRT assay and IHC. Results: Melanoma cell lines and tumors demonstrated heterogeneous expression of CCR7 mRNA by qRT assay. There was strong functional correlation between CCR7 mRNA expression and cell migration induced by CCL21/SLC. IHC evidence of CCR7 expression in primary melanomas significantly (P = 0.02) correlated with Breslow thickness. Assessment of SLN from 55 melanoma patients by qRT assay demonstrated that CCL21/SLC mRNA expression level was significantly (P = 0.008) higher in pathologically melanoma-negative SLNs than in melanoma-positive SLNs. Conclusions: This report demonstrates a potential mechanism for recruitment and homing of CCR7(+) metastatic melanoma cells to tumor-draining lymph nodes, which express CCL21/SLC. The study also suggests that lymph nodes bearing metastasis may suppress CCL21/SLC production.
Erratum: Corrigendum: KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis
Authors: Laura S Shankman, Delphine Gomez, Olga A Cherepanova, Morgan Salmon, Gabriel F Alencar, Ryan M Haskins, Pamela Swiatlowska, Alexandra A C Newman, Elizabeth S Greene, Adam C Straub, Brant Isakson, Gwendalyn J Randolph, Gary K Owens
Journal: Nature Medicine (2016)
Major Vault Protein, in Concert with Constitutively Photomorphogenic 1, Negatively Regulates c-Jun–Mediated Activator Protein 1 Transcription in Mammalian Cells
Authors: Chunling Yi, Shuting Li, Xishu Chen, Erik A.C. Wiemer, Jian Wang, Ning Wei, Xing Wang Deng
Journal: Cancer Research (2005)

Abstract Constitutively photomorphogenic 1 (COP1), a RING finger ubiquitin ligase with substrates including c-Jun and p53, was recently found to be overexpressed in a number of breast and ovarian tumor samples. In addition to its E3 activity, COP1 was also shown to be able to inhibit activator protein 1 (AP-1) transcription. Through an affinity purification method, we have identified major vault protein (MVP) as a novel interacting partner for COP1 in mammalian cells. MVP, also known as lung resistance protein, is the main component of a ribonucleoprotein organelle called vault, and has been implicated in multiple drug resistance in many cancer cell lines and primary tumor samples. The interaction between COP1 and MVP is detectable at the endogenous level and occurs mostly in the cytoplasm. Similar to COP1, MVP inhibits c-Jun accumulation and AP-1 transcription activity. MVP knockout or knockdown cells contain elevated amount of c-Jun and increased AP-1 transcription activity. UV irradiation enhances MVP tyrosine phosphorylation, causes dissociation of COP1 from MVP, and alleviates the inhibitory activity of MVP on AP-1 transcription. Taken together, we propose that MVP, most likely through its interaction with COP1, suppresses c-Jun–mediated AP-1 transcription under unstressed conditions, thereby preventing cells from undergoing stress response.
Notch1 differentially regulates oncogenesis by wildtype p53 overexpression and p53 mutation in grade III hepatocellular carcinoma
Authors: Seung-Oe Lim, Young Min Park, Hyeon Seop Kim, Xiaoyuan Quan, Jeong Eun Yoo, Young Nyun Park, Gi Hong Choi, Guhung Jung
Journal: Hepatology (2011)

The tumor suppressor p53 is a key prognostic factor in hepatocellular carcinoma (HCC), yet only 35% of grade III tumors exhibit mutation of p53. Several other pathways have been implicated in HCC and, among these, the role of the Notch1/Snail pathway remains unclear. Therefore, we investigated the expression of p53, Notch1, and Snail proteins in HCC with regard to both clinical grade and p53 mutational status. Immunoblotting for p53 revealed that, whereas in many tumors increased p53 was a result of p53 mutation, wildtype p53 (p53WT) expression was also frequently elevated in HCCs. Coordinated evaluation of p53, Notch1, and Snail expression suggests that grade III HCC can be subdivided based on the expression of these three proteins. We found that Notch1 expression in HCC tissues and cell lines is differentially affected by p53WT and mutant p53 (p53Mut). Notch1 expression was correlated with p53 expression in cells expressing p53WT, but was not elevated in p53Mut-expressing cells. Virally mediated expression or silencing of p53WT or p53Mut confirmed that p53WT overexpression causes Notch1 up-regulation in HCC. Surprisingly, the consequence of Notch1 overexpression for the proliferative and invasive capacity of HCC cells depends on both the p53 mutational status and activation of the Snail pathway. Conclusion: In the presence of p53WT, Snail/Notch1 activation increased the invasiveness of HCC cells. In contrast, in the absence of p53WT, Notch1 decreased the invasiveness of HCC. Taken together, these findings shed new light on the complex role of the Notch1/Snail axis in HCC and provide a framework for further classifying HCC based on the expression and mutational status of p53 and the expression of Notch1 and Snail. (HEPATOLOGY 2011;53:1352-1362)
Markers Predicting Response to Bacillus Calmette-Guérin Immunotherapy in High-Risk Bladder Cancer Patients: A Systematic Review
Authors: Tahlita C.M. Zuiverloon, Annemieke J.M. Nieuweboer, Hedvig Vékony, Wim J. Kirkels, Chris H. Bangma, Ellen C. Zwarthoff
Journal: European Urology (2011)
Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial
Authors: Josef S Smolen, Andre Beaulieu, Andrea Rubbert-Roth, Cesar Ramos-Remus, Josef Rovensky, Emma Alecock, Thasia Woodworth, Rieke Alten
Journal: The Lancet (2008)
Management of the axilla in early breast cancer patients in the genomic era
Authors: M. Oliveira, J. Cortés, M. Bellet, J. Balmaña, L. De Mattos-Arruda, P. Gómez, E. Muñoz, V. Ortega, J. Pérez, C. Saura, M. Vidal, I.T. Rubio, S. Di Cosimo
Journal: Annals of Oncology (2012)
Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction
Authors: Dara L. Kraitchman, Mitsuaki Tatsumi, Wesley D. Gilson, Takayoshi Ishimori, Dorota Kedziorek, Piotr Walczak, W. Paul Segars, Hunter H. Chen, Danielle Fritzges, Izlem Izbudak, Randell G. Young, Michelle Marcelino, Mark F. Pittenger, Meiyappan Solaiyappan, Raymond C. Boston, Benjamin M.W. Tsui, Richard L. Wahl, Jeff W.M. Bulte
Journal: Circulation (2005)

Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated.With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI.Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.