tbuckley/cabot-search huggingface dataset:
Thyroid hormone enhanced human hepatoma cell motility involves brain-specific serine protease 4 activation via ERK signaling
Authors: Cheng-Yi Chen, I-Hsiao Chung, Ming-Ming Tsai, Yi-Hsin Tseng, Hsiang-Cheng Chi, Chung-Ying Tsai, Yang-Hsiang Lin, You-Ching Wang, Chie-Pein Chen, Tzu-I Wu, Chau-Ting Yeh, Dar-In Tai, Kwang-Huei Lin
Journal: Molecular Cancer (2014)

The thyroid hormone, 3, 3′, 5-triiodo-L-thyronine (T3), has been shown to modulate cellular processes via interactions with thyroid hormone receptors (TRs), but the secretory proteins that are regulated to exert these effects remain to be characterized. Brain-specific serine protease 4 (BSSP4), a member of the human serine protease family, participates in extracellular matrix remodeling. However, the physiological role and underlying mechanism of T3-mediated regulation of BSSP4 in hepatocellular carcinogenesis are yet to be established. The thyroid hormone response element was identified by reporter and chromatin immunoprecipitation assays. The cell motility was analyzed via transwell and SCID mice. The BSSP4 expression in clinical specimens was examined by Western blot and quantitative reverse transcription polymerase chain reaction. Upregulation of BSSP4 at mRNA and protein levels after T3 stimulation is a time- and dose-dependent manner in hepatoma cell lines. Additionally, the regulatory region of the BSSP4 promoter stimulated by T3 was identified at positions -609/-594. BSSP4 overexpression enhanced tumor cell migration and invasion, both in vitro and in vivo. Subsequently, BSSP4-induced migration occurs through the ERK 1/2-C/EBPβ-VEGF cascade, similar to that observed in HepG2-TRα1 and J7-TRα1 cells. BSSP4 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively associated with TRα1 and VEGF to a significant extent. Importantly, a mild association between BSSP4 expression and distant metastasis was observed. Our findings collectively support a potential role of T3 in cancer cell progression through regulation of the BSSP4 protease via the ERK 1/2-C/EBPβ-VEGF cascade. BSSP4 may thus be effectively utilized as a novel marker and anti-cancer therapeutic target in HCC.
OBSERVATIONS ON MONILIA
Authors: I. MUENDE
Journal: British Journal of Dermatology (1931)

Journal Article OBSERVATIONS ON MONILIA Get access I. MUENDE, M.B., B.S., B.Sc. I. MUENDE, M.B., B.S., B.Sc. Pathologist to St. John's Hospital for Diseases of the Skin Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 43, Issue 1, 1 January 1931, Pages 3–19, https://doi.org/10.1111/j.1365-2133.1931.tb09439.x Published: 01 January 1931
MRI inflammation and its relation with measures of clinical disease activity and different treatment responses in patients with ankylosing spondylitis treated with a tumour necrosis factor inhibitor
Authors: Pedro Machado, Robert B M Landewé, Jürgen Braun, Xenofon Baraliakos, Kay-Geert A Hermann, Benjamin Hsu, Daniel Baker, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To investigate the relationship between MRI inflammation and measures of clinical disease activity as well as treatment responses in patients with ankylosing spondylitis (AS) treated with a tumour necrosis factor inhibitor. <h3>Methods</h3> MRI at baseline (n=221), 24 (n=158) and 102 weeks (n=179) were scored for inflammation/activity (MRIa, Berlin scoring system). Treatment responses according to the AS disease activity score (ASDAS), Bath AS disease activity index (BASDAI) and assessment of spondyloarthritis 20 (ASAS20) criteria were calculated. For each treatment response criterion, subgroups of responders and non-responders changes in MRIa scores were compared. <h3>Results</h3> Higher baseline ASDAS and C-reactive protein (CRP) values were associated with higher baseline MRIa scores and with greater decreases in MRIa scores at follow-up. ASDAS and CRP improvements correlated with MRIa improvement. Stronger correlations were observed for CRP. Differences in MRIa change scores between responders and non-responders were greater when subgroups were defined according to ASDAS response than according to BASDAI or ASAS20 response. <h3>Conclusions</h3> MRIa correlates better with CRP than with other measures of disease activity. By including both CRP and patient-reported outcomes in its formula, ASDAS has the advantage of providing combined information on objective and subjective measures. As a status and response measure ASDAS better reflects the spinal inflammatory disease process in AS than other composite measures.
Low minimal inhibitory concentrations of linezolid against multidrug-resistant tuberculosis strains
Authors: Timo Weiss, Nicolas Schönfeld, Ralf Otto-Knapp, Lena Bös, Gudrun Bettermann, Harald Mauch, Torsten Thomas Bauer, Holger Rüssmann
Journal: European Respiratory Journal (2014)

We are following the debate about the administration and the preferred dosage of linezolid in the treatment of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB with great interest. Linezolid is a high potent drug against M. tuberculosis , but its widespread use is limited due to severe side-effects in long-term treatment, which often occurs after the usage of 600 mg twice a day in bacterial disease for >28 days and mainly includes severe haematotoxic effects ( i.e. myelosuppression, anaemia, thrombocytopaenia) or polyneuropathy [1]. However, the current standards in MDR- and XDR-TB require several months of treatment. In addition, the administration of 1200 mg linezolid per day leads to high treatment costs, which limits the usage, especially in low-income countries [1, 2]. Lowering the dosage of linezolid could, therefore, be an effective step towards reducing costs and severe side-effects. Reducing linezolid dose in the treatment of MDR-/XDR-TB to a 300 mg OD could reduce severe side-effects and cost <http://ow.ly/AtU7F>
Dual Functional Monoclonal Antibody PF-04605412 Targets Integrin α5β1 and Elicits Potent Antibody-Dependent Cellular Cytotoxicity
Authors: Gang Li, Lianglin Zhang, Enhong Chen, Jianying Wang, Xin Jiang, Jeffrey H. Chen, Grant Wickman, Karin Amundson, Simon Bergqvist, James Zobel, Dana Buckman, Sangita M. Baxi, Steven L. Bender, Gerald F. Casperson, Dana D. Hu-Lowe
Journal: Cancer Research (2010)

Integrin α5β1 is overexpressed in tumor-associated stroma and cancer cells, and has been implicated in angiogenesis, tumor survival, and metastasis. Antibody-dependent cellular cytotoxicity (ADCC) by immune effector cells has been shown to contribute to clinical efficacy for several IgG1 monoclonal antibody (mAb) therapeutics. Taking advantage of these two mechanisms, we generated a fully human, fragment crystalizable (Fc)-engineered IgG1 mAb, PF-04605412 (PF-5412), which specifically neutralizes α5 and binds the Fcγ receptors (FcγR) with enhanced affinity. In vitro, PF-5412 potently inhibited α5β1-mediated intracellular signaling, cell adhesion, migration, and endothelial cell (EC) tubulogenesis. PF-5412 induced significantly greater ADCC in α5-expressing tumor cells and ECs compared with a wild-type IgG1 (IgG1/wt) or IgG2 of identical antigen specificity. The degree of ADCC correlated with the abundance of natural killer (NK) cells in the peripheral blood mononuclear cells but was independent of donor FcγRIIIa polymorphism. In animal studies, PF-5412 displayed robust and dose-dependent antitumor efficacy superior to that observed with IgG1/wt, IgG2, or IgG4 of identical antigen specificity. The degree of efficacy correlated with α5 expression, macrophage and NK cell infiltration, and NK activity in the tumor. Depletion of host macrophages abrogated antitumor activity, suggesting a critical contribution of macrophage-mediated antitumor activity of PF-5412. Combination of PF-5412 with sunitinib significantly improved antitumor efficacy compared with either agent alone. The dual mechanism of action and robust antitumor efficacy of PF-5412 support its clinical development for the treatment of a broad spectrum of human malignancies.
IgG4 immune response in Churg–Strauss syndrome
Authors: Augusto Vaglio, Johanna D Strehl, Bernhard Manger, Federica Maritati, Federico Alberici, Christian Beyer, Jürgen Rech, Renato A Sinico, Francesco Bonatti, Luisita Battistelli, Jörg H W Distler, Georg Schett, Jochen Zwerina
Journal: Annals of the Rheumatic Diseases (2011)

T-helper type 2 responses are crucial in Churg-Strauss syndrome (CSS) and may enhance the production of IgG4 antibodies. The authors assessed the IgG4 immune response in CSS patients.The authors included 46 consecutive patients with CSS (24 with active and 22 with quiescent disease), 26 with granulomatosis with polyangiitis (GPA, Wegener's), 25 with atopic asthma and 20 healthy controls and determined serum IgG, IgM, IgA, IgE and IgG subclass levels. Tissue infiltration by IgG4 plasma cells was assessed in nine patients with CSS, 10 with GPA, 22 with chronic sinusitis (11 with and 11 without eosinophilia).IgG4 levels were markedly higher in active CSS patients than in controls (p<0.001 vs all control groups). Serum IgG4 correlated with the number of disease manifestations (r=0.52, p=0.01) and the Birmingham vasculitis activity score (r=0.64, p=0.001). Longitudinal analysis in 12 CSS cases showed that both the IgG4 level and IgG4/IgG ratio dropped during disease remission (p=3×10(-5) and p=6×10(-4), respectively). Tissue analysis did not show an increased IgG4 plasma cell infiltration in CSS biopsies compared with control groups.Serum IgG4 levels are markedly elevated in active CSS and correlate with the number of organ manifestations and disease activity.
Refined localization of a punctate palmoplantar keratoderma gene to a 5.06-cM region at 15q22.2-15q22.31
Authors: M. Gao, S. Yang, M. Li, K.L. Yan, Y.X. Jiang, Y. Cui, F.L. Xiao, Y.J. Shen, J.J. Chen, J.B. Liu, S.J. Xu, W. Huang, X.J. Zhang
Journal: British Journal of Dermatology (2005)

Background Punctate palmoplantar keratoderma (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for punctate PPK were recently found to be located on 8q24.13–8q24.21 and 15q22–15q24. However, no genes for this disease have been identified to date. Objectives To refine the previously mapped regions and to identify the disease gene locus in a four‐generation Chinese family with punctate PPK. Methods Genetic linkage analysis was carried out in this family using microsatellite markers on chromosomes 8q and 15q. Two‐point linkage analysis was performed using Linkage programs version 5·10 and the haplotype was constructed using Cyrillic version 2·02 software. Results We failed to confirm our previous locus at 8q24.13–8q24.21, but significant evidence for linkage was observed in the region of 15q with a maximum two‐point LOD score of 5·38 at D15S153 (θ = 0·00). Haplotype analysis localized the punctate PPK locus within the region defined by D15S651 and D15S988. This region overlaps by 5·06 cM with the previously reported punctate PPK region. Conclusions This study refines a disease gene causing punctate PPK to a 5·06‐cM interval at 15q22.2–15q22.31.
Reducing the Risk for Transplantation-Related Mortality After Allogeneic Hematopoietic Cell Transplantation: How Much Progress Has Been Made?
Authors: John T. Horan, Brent R. Logan, Manza-A. Agovi-Johnson, Hillard M. Lazarus, Andrea A. Bacigalupo, Karen K. Ballen, Christopher N. Bredeson, Matthew H. Carabasi, Vikas Gupta, Gregory A. Hale, Hanna Jean Khoury, Mark B. Juckett, Mark R. Litzow, Rodrigo Martino, Philip L. McCarthy, Franklin O. Smith, J. Douglas Rizzo, Marcelo C. Pasquini
Journal: Journal of Clinical Oncology (2011)

Transplantation-related mortality (TRM) is a major barrier to the success of allogeneic hematopoietic cell transplantation (HCT).We assessed changes in the incidence of TRM and overall survival from 1985 through 2004 in 5,972 patients younger than age 50 years who received myeloablative conditioning and HCT for acute myeloid leukemia (AML) in first complete remission (CR1) or second complete remission (CR2).Among HLA-matched sibling donor transplantation recipients, the relative risks (RRs) for TRM were 0.5 and 0.3 for 2000 to 2004 compared with those for 1985 to 1989 in patients in CR1 and CR2, respectively (P < .001). The RRs for all causes of mortality in the latter period were 0.73 (P = .001) and 0.60 (P = .005) for the CR1 and CR2 groups, respectively. Among unrelated donor transplantation recipients, the RRs for TRM were 0.73 (P = .095) and 0.58 (P < .001) for 2000 to 2004 compared with those in 1990 to 1994 in the CR1 and CR2 groups, respectively. Reductions in mortality were observed in the CR2 group (RR, 0.74; P = .03) but not in the CR1 group.Our results suggest that innovations in transplantation care since the 1980s and 1990s have reduced the risk of TRM in patients undergoing allogeneic HCT for AML and that this reduction has been accompanied by improvements in overall survival.
Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices
Authors: Emily Oken, Anna L. Choi, Margaret R. Karagas, Koenraad Mariën, Christoph M. Rheinberger, Rita Schoeny, Elsie Sunderland, Susan Korrick
Journal: Environmental Health Perspectives (2012)

Diverse perspectives have influenced fish consumption choices.We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories.We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns.There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices.Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management interventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.
Differential Functions of <i>Growth Factor Receptor–Bound Protein 7</i> (<i>GRB7</i>) and Its Variant <i>GRB7v</i> in Ovarian Carcinogenesis
Authors: Yajun Wang, David W. Chan, Vincent W.S. Liu, PM Chiu, Hextan Y.S. Ngan
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Aberrant overexpression of growth factor receptor–bound protein 7 (GRB7) and its variant GRB7v has been found in numerous human cancers. The goal of this study was to characterize the functions of GRB7 and GRB7v in the ovarian carcinogenesis and to investigate the differential roles of GRB7 and GRB7v in the modulation of signaling pathways. Experimental Design: Quantitative reverse transcription–PCR, Western blot, and immunohistochemical analyses were used to evaluate the levels of GRB7 and GRB7v. The cellular localization, functions, and signaling pathways regulated by GRB7 and GRB7v were investigated by enforced expression of GRB7 and GRB7v. Results: Quantitative reverse transcription–PCR and Western blot analyses showed that GRB7 and GRB7v were frequently upregulated in ovarian cancer samples. The overexpressed GRB7 (P = 0.009) and GRB7v (P = 0.017) were significantly correlated with high-grade ovarian cancer. Immunohistochemical analysis on ovarian cancer tissue array confirmed that the upregulated GRB7 was significantly correlated with high-grade ovarian cancer (P = 0.001). Confocal microscopy analysis showed that GRB7 and GRB7v predominately localized in cytoplasm of ovarian cancer cells, consistent with their roles as signaling adaptors. Enforced expression of GRB7 promoted cell proliferation, migration, and invasion, whereas GRB7v only increased cell proliferation and anchorage-independent growth ability. With the treatment of specific kinase inhibitors, we showed that both GRB7 and GRB7v promoted cell proliferation through activating extracellular signal-regulated kinase signaling, whereas GRB7 enhanced cell migration/invasion by activating c-Jun NH2 terminal kinase signaling. Conclusions: Our studies implicate that the overexpressed GRB7 and GRB7v are associated with high-grade tumors and exert distinct tumorigenic functions through regulating different signaling pathways in ovarian cancer cells. Clin Cancer Res; 16(9); 2529–39. ©2010 AACR.
A randomized trial comparing the impact of a nonionic (iomeprol) versus an ionic (ioxaglate) low osmolar contrast medium on abrupt vessel closure and ischemic complications after coronary angioplasty
Authors: Rainer Schräder, Ingo Esch, Roland Ensslen, Wolf Andreas Fach, Hartmut Merle, Detlef Scherer, Horst Sievert, Hans Friedrich Spies, Harald E Zeplin
Journal: Journal of the American College of Cardiology (1999)
PECAM-1 (CD31) Homophilic Interaction Up-Regulates α6β1 on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α6 Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane
Authors: John Dangerfield, Karen Y. Larbi, Miao-Tzu Huang, Ann Dewar, Sussan Nourshargh
Journal: The Journal of Experimental Medicine (2002)

Platelet-endothelial cell adhesion molecule (PECAM)-1 has been implicated in leukocyte migration through the perivascular basement membrane (PBM) though the mechanisms involved are unclear. The present results demonstrate that the ability of α6 integrins to mediate neutrophil migration through the PBM is PECAM-1 dependent, a response associated with PECAM-1–mediated increased expression of α6β1 on transmigrating neutrophils in vivo. An anti-α6 integrins mAb (GoH3) inhibited (78%, P &amp;lt; 0.001) neutrophil migration through interleukin (IL)-1β–stimulated cremasteric venules, primarily at the level of the PBM, as analyzed by intravital and electron microscopy. In PECAM-1–deficient mice (KO), a reduced level of neutrophil transmigration elicited by IL-1β (4-h reaction) was observed in both the cremaster muscle (55% inhibition, P &amp;lt; 0.05) and in the peritoneum (57% inhibition, P &amp;lt; 0.01) but GoH3 had no additional inhibitory effect on these responses. FACS® analysis of neutrophils demonstrated increased expression of α6β1 on transmigrated peritoneal neutrophils, as compared with blood neutrophils, in wild-type but not KO mice even though neutrophils from both strains of mice exhibited comparable levels of intracellular expression of α6 as observed by immunofluorescent staining and confocal microscopy. Furthermore, mice deficient in either leukocyte or endothelial cell PECAM-1, as developed by bone marrow transplantation, demonstrated a similar level of reduced neutrophil transmigration and expression of α6β1 on transmigrated neutrophils as that detected in KO mice. The results demonstrate a role for PECAM-1 homophilic interaction in neutrophil transmigration and increased expression of α6β1 on the cell surface of transmigrated neutrophils in vivo, a response that could contribute to the mechanism of PECAM-1–mediated neutrophil migration through the PBM.
Cytotoxic T cell response to minor histocompatibility antigens: apparent lack of H-2 restriction in killers stimulated by membrane fragments.
Authors: L M Pilarski, D Vergidis
Journal: The Journal of Experimental Medicine (1982)

The secondary cytotoxic T cell response of BALB/c to B10.D2 or DBA/2 minor histocompatibility antigens in vitro requires the participation of an adherent cell. Nylon wool-passed spleen cells were only able to respond to nonadherent intact stimulator cells, or to membrane fragments derived from those cells, if a syngeneic adherent cell were present in the cultures. When the H-2 restriction properties of cytotoxic cells generated in response to various types of stimulation were analyzed, it was found that responses to B10.D2 or DBA/2 intact cells were always H-2 restricted. Responses to syngeneic adherent cells presenting B10.D2 or DBA.2 freeze-thaw antigen were either entirely or predominantly lacking in H-2 restriction as defined by efficient competition by B10 (H-2b) cold target cells. These unrestricted killers appeared to recognize minor histocompatibility as an independent determinant rather than as an H-2d/minors moiety cross-reaction with H-2b, because they were not absorbed by BALB.B (H-2b) macrophage monolayers, but were absorbed by B10 monolayers. Similarly, B10 but not BALB.B cold targets were able to compete for the anti-B10.D2 killers. These experiments eliminate the possibility that the lack of restriction was due to an H-2b restricted receptor cross-reactive with H-2b. Possible models to explain these findings are discussed.
Proinflammatory Phenotype of Perivascular Adipocytes
Authors: Tapan K. Chatterjee, Lynn L. Stoll, Gerene M. Denning, Allan Harrelson, Andra L. Blomkalns, Gila Idelman, Florence G. Rothenberg, Bonnie Neltner, Sara A. Romig-Martin, Eric W. Dickson, Steven Rudich, Neal L. Weintraub
Journal: Circulation Research (2009)

Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of antiinflammatory adiponectin is markedly reduced, whereas that of proinflammatory cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro–differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, 2 weeks of high-fat feeding caused further reductions in adipocyte-associated gene expression, while upregulating proinflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened proinflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.