tbuckley/cabot-search huggingface dataset:
Heterogeneous lobular distribution of hepatocytes expressing acute-phase genes during the acute inflammatory reaction.
Authors: D Bernuau, L Legrès, Y Lamri, N Giuily, G Fey, G Feldmann
Journal: The Journal of Experimental Medicine (1989)

Functional heterogeneity in the lobule with regard to plasma protein synthesis is still debated. Therefore, we have localized in liver sections from normal rats and from rats with turpentine-induced AIR the mRNA and protein products of three genes with different alterations in their hepatic expression during an AIR: alpha 2M and alpha 1PI, two positively reacting acute-phase genes, and alpha 1I3, a negative acute-phase reactant. In normal liver, all hepatocytes expressed alpha 2M and alpha 1I3 mRNA, but a preferential expression of alpha 2M and alpha 1I3 mRNA and protein in the PP and ML zones was observed. During an AIR, the level of alpha 2M mRNA increased fourfold in the cytoplasm of PP and ML hepatocytes, while the level of cytoplasmic alpha 1I3 mRNA was decreased about fourfold in the same zones, with parallel variations in the expression of the corresponding proteins. In contrast, no significant modulation of the RNA and protein concentrations of both genes was detected in PV areas. alpha 1PI mRNA was expressed at the same levels in the three lobular zones in normal liver, but staining for the alpha 1PI protein was more intense in the PV zones. During the acute-phase response alpha 1PI mRNA levels were increased twofold in all three lobular zones, and alpha 1PI staining became homogeneous within the lobule. These results demonstrate that the location of a hepatocyte with the liver lobule can influence the expression of the three genes under study both at pre- and post-translational levels, in basal conditions, as well as during modulation of their expression during the inflammatory reaction.
Specific Lyt 123 cells are involved in protection against Listeria monocytogenes and in delayed-type hypersensitivity to listerial antigens.
Authors: S H Kaufmann, M M Simon, H Hahn
Journal: The Journal of Experimental Medicine (1979)

Specific anti-Lyt antisera and complement were used to determine the Lyt phenotype of peritoneal exudate T lymphocytes from Listeria monocytogenes-immune mice. It was found that Lyt 123+ T cells are crucially involved both in protection against listerial infection and in delayed-type hypersensitivity (DTH) to listerial antigens. Thus, both functions critically depend on a T-cell subclass phenotypically different from that which mediates DTH to noninfectious antigens and help in antibody formation on the one hand, as well as those T cells mediating cytotoxic reactions on the other.
Kaposi-like acroangiodermatitis induced by a suction-socket prosthesis
Authors: A. Badell, J. Marcoval, J. Graells, A. Moreno, J. Peyri
Journal: British Journal of Dermatology (1994)

Journal Article Kaposi‐like acroangiodermatitis induced by a suction‐socket prosthesis Get access A. Badell, A. Badell Departments of Dermatology, Hospital Princeps d'Espanya, Ciutat Sanitària i Universitària de Bellvitge, Feixa Llarga, s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar J. Marcoval, J. Marcoval Departments of Dermatology, Hospital Princeps d'Espanya, Ciutat Sanitària i Universitària de Bellvitge, Feixa Llarga, s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar J. Graells, J. Graells Departments of Dermatology, Hospital Princeps d'Espanya, Ciutat Sanitària i Universitària de Bellvitge, Feixa Llarga, s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Moreno, A. Moreno Pathology, Hospital Princeps d'Espanya, Ciutat Sanitària i Universitària de Bellvitge, Feixa Llarga, s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar J. Peyri J. Peyri Departments of Dermatology, Hospital Princeps d'Espanya, Ciutat Sanitària i Universitària de Bellvitge, Feixa Llarga, s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 6, 1 December 1994, Pages 915–917, https://doi.org/10.1111/j.1365-2133.1994.tb08608.x Published: 01 December 1994
Ecological Momentary Assessment
Authors: Saul Shiffman, Arthur A. Stone, Michael R. Hufford
Journal: Annual Review of Clinical Psychology (2007)

Assessment in clinical psychology typically relies on global retrospective self-reports collected at research or clinic visits, which are limited by recall bias and are not well suited to address how behavior changes over time and across contexts. Ecological momentary assessment (EMA) involves repeated sampling of subjects’ current behaviors and experiences in real time, in subjects’ natural environments. EMA aims to minimize recall bias, maximize ecological validity, and allow study of microprocesses that influence behavior in real-world contexts. EMA studies assess particular events in subjects’ lives or assess subjects at periodic intervals, often by random time sampling, using technologies ranging from written diaries and telephones to electronic diaries and physiological sensors. We discuss the rationale for EMA, EMA designs, methodological and practical issues, and comparisons of EMA and recall data. EMA holds unique promise to advance the science and practice of clinical psychology by shedding light on the dynamics of behavior in real-world settings.
Inactivation of <i>SMAD4</i> Tumor Suppressor Gene During Gastric Carcinoma Progression
Authors: Li-Hui Wang, Seok-Hyung Kim, Jung Hyun Lee, Yoon-La Choi, Young Chul Kim, Tae Sung Park, Yun-Chul Hong, Chun-Fu Wu, Young Kee Shin
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Mothers against decapentaplegic homologue 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study is to more precisely characterize its role in the development and progression of human gastric carcinoma. Experimental Design: The expression of SMAD4 was investigated in 283 gastric adenocarcinomas and related lesions, as well as in 9 gastric carcinoma cell lines. We also analyzed the methylation status of SMAD4 gene by using methylation-specific PCR, examined loss of heterozygosity (LOH) of this gene locus by using a vicinal marker, and detected exon mutation of SMAD4 through exon-by-exon amplification. Moreover, we assessed whether MG132, a proteasome inhibitor, affected the SMAD4 protein level. Results: We found loss of SMAD4 protein expression in the cytoplasm (36 of 114, 32%) and in the nucleus (46 of 114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. In addition, we found that LOH (20 of 70, 29%) and promoter hypermethylation (4 of 73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels were also affected in certain gastric carcinoma cell lines following incubation with MG132. Conclusion: Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas was due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.
A pivotal role for antigen-presenting cells overexpressing SOCS3 in controlling invariant NKT cell responses during collagen-induced arthritis
Authors: S. Veenbergen, M. B. Bennink, A. J. Affandi, N. Bessis, J. Biton, O. J. Arntz, W. B. van den Berg, F. A. J. van de Loo
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Suppressor of cytokine signalling (SOCS) proteins constitute a class of intracellular proteins that are key physiological regulators of immune cell function. It has previously been shown that antigen-presenting cells (APCs) overexpressing SOCS3 steer T helper immune responses and protect against experimental arthritis. A study was undertaken to investigate the contribution of SOCS3 in regulating invariant natural killer T (iNKT) cell responses during collagen-induced arthritis (CIA). <h3>Methods</h3> DBA/1 mice were immunised with type II collagen and adenoviruses encoding SOCS3 were administered intravenously before the clinical onset of arthritis. Murine APCs overexpressing SOCS3 were co-cultured with an iNKT cell hybridoma and interleukin 2 (IL-2) release was measured by Luminex multi-analyte technology. The frequency and activation of primary iNKT cells was assessed by flow cytometry. Murine APCs were analysed for cytokine and CD1d expression following viral SOCS3 gene transfer. <h3>Results</h3> Viral overexpression of SOCS3 in APCs resulted in reduced activation of the iNKT cell hybridoma. Importantly, during initiation of CIA, adenovirus-mediated overexpression of SOCS3 in hepatic and splenic APCs inhibited iNKT cell expansion in both organs. The iNKT cell population from SOCS3-treated mice showed low expression of the early activation marker CD69 and primary liver iNKT cells produced less interferon γ and IL-4 upon α-galactosylceramide stimulation. No differences in CD1d surface expression were observed, but SOCS3-transduced APCs produced decreased levels of proinflammatory cytokines and increased levels of IL-10. <h3>Conclusion</h3> These results demonstrate a critical role for SOCS3 in controlling the immunostimulatory capacities of APCs, which has direct implications for the effector function of iNKT cells during arthritis.
Comparative Study between DNA Copy Number Aberrations Determined by Quantitative Microsatellite Analysis and Clinical Outcome in Patients with Stomach Cancer
Authors: Seiji Suzuki, Kaku Egami, Koji Sasajima, Mohammad Ghazizadeh, Hajime Shimizu, Hidehiro Watanabe, Hirokazu Hasegawa, Shinya Iida, Takeshi Matsuda, Yuji Okihama, Masaru Hosone, Kazuo Shimizu, Oichi Kawanami, Takashi Tajiri
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We detected the relative DNA copy numbers (RCNs) at target loci in patients with stomach cancer with quantitative microsatellite analysis. We additionally clarified the relationship between DNA copy number aberrations and the clinical outcome of the patients. Experimental Design: Fresh frozen samples were obtained from 30 patients who had undergone surgery for stomach cancer. Seven microsatellite loci in chromosomes 8q, 16q, and 20q and one gene-specific locus (ZNF217) were selected as the target loci. The DNA copy number was obtained relatively to a pooled reference consisting of six microsatellite primer sets selected from the regions where few aberrations have been reported in comparative genomic hybridization analysis. On the basis of the TaqMan PCR system, the internal probes used were carrying donor (6-carboxyfluorescein) and acceptor (6-carboxytetramethylrhodamine) fluorescent molecules complementary to CA repeats in the microsatellite markers and to one gene-specific oligomer in the gene-specific marker. Results: Chromosome 8q gain, 20q gain, and 16q loss were detected in 18 (60.0%), 8 (26.7%), and 13 (43.3%) cases, respectively. Gains in the RCNs of D8S1801 and D8S1724 were most frequently found (36.7%). There was a significant correlation between the loss of D16S3026 and reduced survival duration (P = 0.0158), and the simultaneous aberrations of D8S1801 gain and D16S3026 loss (double marker positive) was significantly associated with reduced survival duration (P = 0.0008). According to Cox proportional hazards model, the double marker positive was a significant and independent factor indicating an unfavorable prognostic factor (relative risk, 17.176; 95% confidence interval, 2.782–106.026; P = 0.0022). Conclusion: RCN aberrations in tumor tissues determined by quantitative microsatellite analysis enable identification of the prognostic factors that correlate with clinical outcome of the patients with stomach cancer.
Intragraft Levels of Foxp3 mRNA Predict Progression in Renal Transplants with Borderline Change
Authors: Hicham Mansour, Sébastien Homs, Dominique Desvaux, Cécile Badoual, Karine Dahan, Marie Matignon, Vincent Audard, Philippe Lang, Philippe Grimbert
Journal: Journal of the American Society of Nephrology (2008)

The optimal therapeutic management of borderline lymphocytic infiltrates in renal allografts, described by Banff criteria, is unknown, largely because of the inability to predict clinical outcome in these cases. For determination of molecular factors that may predict outcome in cases of borderline change histology, mRNA levels of Foxp3, Granzyme B, IFN-γ, IL-23, and RORγt were measured in renal tissue from 46 untreated patients. Twenty-five patients were considered "nonprogressive," defined by a serum creatinine that remained <110% of baseline during the 40 d after biopsy. Twenty-one patients were considered "progressive," defined by an increase in serum creatinine >110% from baseline and by repeat histologic examination within 40 d showing progression toward acute rejection. Only Foxp3 mRNA levels were significantly higher in nonprogressors than in progressors (P = 0.001). Analysis of receiver operating characteristic curves demonstrated that the outcome for patients with biopsies showing borderline change could be predicted with 90% sensitivity and 79.1% specificity using the optimal Foxp3 mRNA cutoff value. Our findings suggest that the measurement of Foxp3 mRNA offers a means of improving prediction of outcome of borderline change.
G Protein–Coupled Receptor Kinase 2 Ablation in Cardiac Myocytes Before or After Myocardial Infarction Prevents Heart Failure
Authors: Philip W. Raake, Leif E. Vinge, Erhe Gao, Matthieu Boucher, Giuseppe Rengo, Xiongwen Chen, Brent R. DeGeorge, Scot Matkovich, Steven R. Houser, Patrick Most, Andrea D. Eckhart, Gerald W. Dorn, Walter J. Koch
Journal: Circulation Research (2008)

Myocardial G protein–coupled receptor kinase (GRK)2 is a critical regulator of cardiac β-adrenergic receptor (βAR) signaling and cardiac function. Its upregulation in heart failure may further depress cardiac function and contribute to mortality in this syndrome. Preventing GRK2 translocation to activated βAR with a GRK2-derived peptide that binds G β γ (βARKct) has benefited some models of heart failure, but the precise mechanism is uncertain, because GRK2 is still present and βARKct has other potential effects. We generated mice in which cardiac myocyte GRK2 expression was normal during embryonic development but was ablated after birth (αMHC-Cre×GRK2 fl/fl) or only after administration of tamoxifen (αMHC-MerCreMer×GRK2 fl/fl) and examined the consequences of GRK2 ablation before and after surgical coronary artery ligation on cardiac adaptation after myocardial infarction. Absence of GRK2 before coronary artery ligation prevented maladaptive postinfarction remodeling and preserved βAR responsiveness. Strikingly, GRK2 ablation initiated 10 days after infarction increased survival, enhanced cardiac contractile performance, and halted ventricular remodeling. These results demonstrate a specific causal role for GRK2 in postinfarction cardiac remodeling and heart failure and support therapeutic approaches of targeting GRK2 or restoring βAR signaling by other means to improve outcomes in heart failure.
Possible Role of Human Natural Anti-Gal Antibodies in the Natural Antitumor Defense System
Authors: V. Castronovo, C. Colin, B. Parent, J.-M. Foidart, R. Lambotte, P. Mahieu
Journal: JNCI Journal of the National Cancer Institute (1989)

Expression of Galα1–3Gal cell surface residues has been correlated with the metastatic potential of murine tumor cells. We report that Galαl–3Gal residues are expressed at the cell surface of malignant human cancer cells, including four cell lines and 50% of the malignant breast specimens obtained by aspiration biopsy. In contrast, all benign breast biopsies and normal cells were Galα1–3Gal negative. Affinity-purified anti-α-galactosyl IgG (anti-Gal) antibody, which specifically recognizes Galα1–3Gal residues, significantly inhibited cell attachment in two in vitro assays thought to indicate tumor cell extravasation of the circulatory system during the metastatic process: attachment to perfused human umbilical vein endothelium, and attachment to isolated laminin. Since anti-Gal antibody is a natural component of all human sera, we propose that it may be part of the natural antitumor defense system in humans. [J Natl Cancer Inst 1989;81:212–216]
Phase II Trial of Sorafenib in Metastatic Thyroid Cancer
Authors: Richard T. Kloos, Matthew D. Ringel, Michael V. Knopp, Nathan C. Hall, Mark King, Robert Stevens, Jiachao Liang, Paul E. Wakely, Vasyl V. Vasko, Motoyasu Saji, Jennifer Rittenberry, Lai Wei, Daria Arbogast, Minden Collamore, John J. Wright, Michael Grever, Manisha H. Shah
Journal: Journal of Clinical Oncology (2009)

Purpose Based on the pivotal role of Ras-Raf-MAP-ERK signaling and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC), we conducted a phase II clinical trial of sorafenib targeting RAF and VEGF receptor kinases in PTC. Patients and Methods The primary end point was the objective response rate. Secondary end points included response correlation with serum thyroglobulin (Tg); functional imaging; tumor genotype; and signaling inhibition in tumor biopsies. Using a Simon minimax two-stage design, 16 or 25 chemotherapy-naïve metastatic PTC patients were to be enrolled in arm A (accessible tumor for biopsy). Arm B patients had other subtypes of thyroid carcinoma or prior chemotherapy, and did not require tumor biopsies. Patients received 400 mg orally twice per day of sorafenib. Response was assessed every 2 months using RECIST (Response Evaluation Criteria in Solid Tumors). Results Of 41 PTC patients, six patients had a partial response (PR; 15%; 95% CI, 6 to 29) and 23 patients (56%; 95% CI, 40 to 72) had stable disease longer than 6 months. Median duration of PR was 7.5 months (range, 6 to 14). Median progression-free survival was 15 months (95% CI, 10 to 27.5). In 14 (78%) of 18 Tg-assessable PTC patients, Tg declined more than 25%. Common grade 3 adverse events included hand-foot skin reaction, musculoskeletal pain, and fatigue. BRAF mutation was detected in 17 (77%) of 22 PTCs analyzed. Four of 10 paired tumor biopsies from PTC patients showed a reduction in levels of vascular endothelial growth factor receptor phosphorylation, ERK phosphorylation, and in VEGF expression during sorafenib therapy. No PRs were noted among non-PTC patients. Conclusion Sorafenib is reasonably well-tolerated therapy with clinical and biologic antitumor activity in metastatic PTC.
Evolution and phylogenetic utility of the period gene in Lepidoptera
Authors: J C Regier, Q Q Fang, C Mitter, R S Peigler, T P Friedlander, M A Solis
Journal: Molecular Biology and Evolution (1998)

Evolution and phylogenetic utility of the period gene are explored through sequence analysis of a relatively conserved 909-bp fragment in 26 lepidopteran species. Taxa range from tribes to superfamilies, primarily within the putative clade Macrolepidotera plus near outgroups, and include both strongly established and problematic groupings. Their divergence dates probably range from the late Cretaceous through much of the Tertiary. Comparisons within the same set of closely related species show that amino acid substitutions in period occur 4.9 and 44 times as frequently as they do in two other nuclear genes--dopa decarboxylase and elongation factor-1 alpha, respectively. In contrast, rates of observed synonymous substitution are within 60% of each other for these three genes. Synonymous changes in period approach saturation by the family level, whereas nonsynonymous and amino acid divergences across the Macrolepidoptera are less than half the maximal values reported for this gene. Phylogenetic analyses of period strongly supported groupings at the family level and below. In contrast to previous analyses at this level with other nuclear genes, much of the information lies in nonsynonymous change. Relationships up to the superfamily level were recovered with decreasing effectiveness, and little, if any, signal was apparent regarding relationships among superfamilies. This could reflect rapid radiation of the superfamilies, however, rather than saturation in the period locus; thus, period, in combination with other genes, remains a plausible candidate for approaching the difficult problems of lepidopteran family and superfamily relationships.
T lymphocytes of recipient origin may contribute to the recovery of specific immune response toward viruses and fungi in children undergoing cord blood transplantation
Authors: Daniela Montagna, Franco Locatelli, Antonia Moretta, Daniela Lisini, Carlo Previderè, Pierangela Grignani, Piero DeStefano, Giovanna Giorgiani, Enrica Montini, Sara Pagani, Patrizia Comoli, Rita Maccario
Journal: Blood (2004)
Molecular Chaperone gp96 Is a Novel Therapeutic Target of Multiple Myeloma
Authors: Yunpeng Hua, Shai White-Gilbertson, Joshua Kellner, Saleh Rachidi, Saad Z. Usmani, Gabriela Chiosis, Ronald DePinho, Zihai Li, Bei Liu
Journal: Clinical Cancer Research (2013)

Abstract Purpose: gp96 (grp94) is a key downstream chaperone in the endoplasmic reticulum (ER) to mediate unfolded protein response (UPR) and the pathogenesis of multiple myeloma is closely linked to dysregulated UPR. In this study, we aimed to determine the roles of gp96 in the initiation and progression of multiple myeloma in vivo and in vitro. Experimental Design: We generated a mouse model with overexpression of XBP1s and conditional deletion of gp96 in B-cell compartment simultaneously to identify the roles of gp96 in the development of multiple myeloma in vivo. Using a short hairpin RNA (shRNA) system, we silenced gp96 in multiple human multiple myeloma cells and examined the effect of gp96 knockdown on multiple myeloma cells by cell proliferation, cell-cycle analysis, apoptosis assay, immunohistochemistry, and human myeloma xenograft model. The anticancer activity of gp96 selective inhibitor, WS13, was evaluated by apoptosis assay and MTT assay. Results: Genetic deletion of gp96 in XBP1s-Tg mice attenuates multiple myeloma. Silencing of gp96 causes severe compromise in human multiple myeloma cell growth through inhibiting Wnt-LRP-survivin pathway. We also confirmed that knockdown of gp96 decreased human multiple myeloma growth in a murine xenograft model. The targeted gp96 inhibitor induced apoptosis and blocked multiple myeloma cell growth, but did not induce apoptosis in pre-B leukemic cells. We have demonstrated that myeloma growth is dependent on gp96 both genetically and pharmacologically. Conclusions: gp96 is essential for multiple myeloma cell proliferation and survival, suggesting that gp96 is a novel therapeutic target for multiple myeloma. Clin Cancer Res; 19(22); 6242–51. ©2013 AACR.