tbuckley/cabot-search huggingface dataset:
iVici: Interrelational Visualization and Correlation Interface.
Authors: Kirill Tarassov, Stephen W Michnick
Journal: Genome biology (2005)

Abstract We have developed an application, iVici, to analyze cellular networks represented as addressable symmetric or asymmetric two-dimensional matrices. iVici was designed to permit simultaneous visualization and correlation of multiple datasets, representing any relationship between a set of genes, mRNAs, or proteins. Visual overlay of datasets and addressable access to gene annotations permits comparison of networks of different types (for example protein-protein interactions and genetic networks) or investigation of the dynamic reorganization of a particular network.
Severe fletcher factor (plasma prekallikrein) deficiency with partial deficiency of hageman factor (factor xii): Report of a case with observation on in vivo and in vitro leukocyte chemotaxis
Authors: Man‐Chiu Poon, Michael R. Moore, Robert P. Castleberry, Aubrey Lurie, Shu Tsong Huang, Joyce Lehmeyer
Journal: American Journal of Hematology (1982)

Abstract A case of cross‐reacting material‐negative Fletcher trait with additional partial deficiency of Hageman factor (HF, Factor XII) is described. Although the patient presented with a recent history of frequent epistaxis, he had no other personal or family history of a tendency toward bleeding or infection. Similar to other cases of Fletcher trait, his plasma showed a markedly prolonged partial thromboplastin time which could be corrected by prolonged incubation with the surface‐activator kaolin. Surface‐induced fibrinolysis, amidolysis of α‐N‐benzoyl‐proline‐ L ‐phenylalanine‐ L ‐arginine‐p‐nitro‐ anilide, and cold‐promoted enhancement of factor VII activity, reactions requiring the presence in the plasma of Fletcher factor (pre‐kallikrein), in addition to Hageman factor and Fitzgerald factor (high‐molecular weight kininogen), were also defective. In vivo chemotaxis of polymorphonuclear leukocytes and monocytes (Rebuck's skin window technique) in response to skin abrasions was defective, but was normal when diphtheria‐tetanus toxoid was also applied. In vitro leukocyte chemotaxis (Boyden chamber technique) in response to normal or patient's own serum activated with zymosan was normal. Together with previous observations that kallikrein generated chemotactic activity, possibly via activation of C5, the present observations suggest that prekallikrein activation may be important for in vivo leukocyte chemotactic response to skin abrasion. The inheritance of Fletcher trait in this patient is unclear. Although the father was an apparent heterozygote, the mother was completely normal for Fletcher factor procoagulant activity and antigen. The mild Hageman factor deficiency in the patient did not contribute significantly to the plasma defects described and was likely inherited from the father who had a low HF procoagulant activity.
Abnormal Cortical Development after Premature Birth Shown by Altered Allometric Scaling of Brain Growth
Authors: Olga Kapellou, Serena J Counsell, Nigel Kennea, Leigh Dyet, Nadeem Saeed, Jaroslav Stark, Elia Maalouf, Philip Duggan, Morenike Ajayi-Obe, Jo Hajnal, Joanna M Allsop, James Boardman, Mary A Rutherford, Frances Cowan, A. David Edwards
Journal: PLoS Medicine (2006)

Background We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. Methods and Findings We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25–1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. Conclusions Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.
OX40 ligand expressed in glioblastoma modulates adaptive immunity depending on the microenvironment: a clue for successful immunotherapy
Authors: Ichiyo Shibahara, Ryuta Saito, Rong Zhang, Masashi Chonan, Takuhiro Shoji, Masayuki Kanamori, Yukihiko Sonoda, Toshihiro Kumabe, Masahiko Kanehira, Toshiaki Kikuchi, Takanori So, Takashi Watanabe, Hiroaki Takahashi, Erina Iwabuchi, Yuetsu Tanaka, Yukiko Shibahara, Hironobu Sasano, Naoto Ishii, Teiji Tominaga
Journal: Molecular Cancer (2015)

Glioblastoma is the most malignant human brain tumor and has a dismal prognosis; however, some patients show long-term survival. The interaction between the costimulatory molecule OX40 and its ligand OX40L generates key signals for T-cell activation. The augmentation of this interaction enhances antitumor immunity. In this present study, we explored whether OX40 signaling is responsible for antitumor adaptive immunity against glioblastoma and also established therapeutic antiglioma vaccination therapy. Tumor specimens were obtained from patients with primary glioblastoma (n = 110) and grade III glioma (n = 34). Quantitative polymerase chain reaction (PCR), flow cytometry, and immunohistochemistry were used to analyze OX40L expression in human glioblastoma specimens. Functional consequences of OX40 signaling were studied using glioblastoma cell lines, mouse models of glioma, and T cells isolated from human subjects and mice. Cytokine production assay with mouse regulatory T cells was conducted under hypoxic conditions (1.5% O2). OX40L mRNA was expressed in glioblastoma specimens and higher levels were associated with prolonged progression-free survival of patients with glioblastoma, who had undergone gross total resection. In this regard, OX40L protein was expressed in A172 human glioblastoma cells and its expression was induced under hypoxia, which mimics the microenvironment of glioblastoma. Notably, human CD4 T cells were activated when cocultured in anti-CD3-coated plates with A172 cells expressing OX40L, as judged by the increased production of interferon-γ. To confirm the survival advantage of OX40L expression, we then used mouse glioma models. Mice bearing glioma cells forced to express OX40L did not die during the observed period after intracranial transplantation, whereas all mice bearing glioma cells lacking OX40L died. Such a survival benefit of OX40L was not detected in nude mice with an impaired immune system. Moreover, compared with systemic intraperitoneal injection, the subcutaneous injection of the OX40 agonist antibody together with glioma cell lysates elicited stronger antitumor immunity and prolonged the survival of mice bearing glioma or glioma-initiating cell-like cells. Finally, OX40 triggering activated regulatory T cells cultured under hypoxia led to the induction of the immunosuppressive cytokine IL10. Glioblastoma directs immunostimulation or immunosuppression through OX40 signaling, depending on its microenvironment.
T-cell chronic lymphocytic leukaemia with pulmonary involvement and relapsing BOOP
Authors: E. Vaiman, M. Odeh, D. Attias, Y. Ben-Arie, A. Oliven
Journal: European Respiratory Journal (1999)

We report on a case of T-cell chronic lymphocytic leukaemia involving the lung, with clinical, radiological and histological evidence of relapsing bronchiolitis obliterans-organizing pneumonia in a 70-yr-old female. Pulmonary disease was the major clinical manifestation of this chronic lymphocytic leukaemia. The first two episodes of the patient9s pulmonary disorder resolved without treatment, and the third episode was treated with cytotoxic agents as part of the leukaemia treatment regimen. Two additional episodes of the pulmonary disorder occurred; both responded to prednisone.
Shared reactivity of Vδ2neg γδ T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells
Authors: Franck Halary, Vincent Pitard, Dorota Dlubek, Roman Krzysiek, Henri de la Salle, Pierre Merville, Claire Dromer, Dominique Emilie, Jean-François Moreau, Julie Déchanet-Merville
Journal: The Journal of Experimental Medicine (2005)

Long-lasting expansion of Vdelta2(neg) gammadelta T cells is a hallmark of cytomegalovirus (CMV) infection in kidney transplant recipients. The ligands of these cells and their role remain elusive. To better understand their immune function, we generated gammadelta T cell clones from several transplanted patients. Numerous patient Vdelta1(+), Vdelta3(+), and Vdelta5(+) gammadelta T cell clones expressing diverse Vgamma chains, but not control Vgamma9Vdelta2(+) T clones, displayed strong reactivity against CMV-infected cells, as shown by their production of tumor necrosis factor-alpha. Vdelta2(neg) gammadelta T lymphocytes could also kill CMV-infected targets and limit CMV propagation in vitro. Their anti-CMV reactivity was specific for this virus among herpesviridae and required T cell receptor engagement, but did not involve major histocompatibility complex class I molecules or NKG2D. Vdelta2(neg) gammadelta T lymphocytes expressed receptors essential for intestinal homing and were strongly activated by intestinal tumor, but not normal, epithelial cell lines. High frequencies of CMV- and tumor-specific Vdelta2(neg) gammadelta T lymphocytes were found among patients' gammadelta T cells. In conclusion, Vdelta2(neg) gammadelta T cells may play a role in protecting against CMV and tumors, probably through mucosal surveillance of cellular stress, and represent a population that is largely functionally distinct from Vgamma9Vdelta2(+) T cells.
Pk11195, a mitochondrial benzodiazepine receptor antagonist, reduces apoptosis threshold in Bcl-XL and Mcl-1 expressing human cholangiocarcinoma cells
Authors: A C Okaro
Journal: Gut (2002)

Cholangiocarcinoma cells express high levels of the antiapoptotic proteins Bcl-X(L) and Mcl-1 and are markedly chemo- and radioresistant. Mitochondria have emerged as central players in apoptosis. Antiapoptotic members of the Bcl-2 protein family localise to the outer mitochondrial membrane and regulate mitochondrial release of apoptogenic proteins. Mitochondrial benzodiazepine receptor (mBzR) ligands have been shown to reverse Bcl-2 action and facilitate apoptosis.We evaluated the ability of the mBzR antagonist Pk11195 to overcome preapoptotic mitochondrial dysfunction in Egi-1 and Tfk-1, two human cholangiocarcinoma cell lines expressing high levels of Bcl-X(L) and Mcl-1.Cells growing in culture were used to perform in vitro experiments over 48-96 hours following treatment. The cytotoxic agents used were 5 fluorouracil 10 microM and etoposide (Vp16) 10 microM, together with ultraviolet and 0.5-1 Gy x ray irradiation with or without 75 microM Pk11195. Apoptosis and mitochondrial dysfunction were measured at single cell resolution by flow cytometry using the mitochondrial fluorochrome DiOC6(3). Severe combined immunodeficient non-obese diabetic (SCID-NOD) mice with subcutaneous xenografts using the Egi-1 and Tfk-1 cell lines were treated with etoposide with or without addition of Pk11195 over a 72 hour period during which time the xenograft growth patterns were monitored.In vitro, the effect of Pk11195 on induction of apoptosis in cholangiocarcinoma cells following stimulation by chemotherapy or radiotherapy was found to be both time and dose dependent, with Pk11195 increasing rates of apoptosis by 50-95%. Intraperitoneal administration of Pk11195 in combination with Vp16 was found to increase the growth inhibiting effects of Vp16 on xenografts during the treatment phase. PK11195 75 microM on its own had no intrinsic cytotoxic efficacy.This is the first study to demonstrate that functional antagonism of coexpressed Bcl-X(L) and Mcl-1 proteins using the mBzR antagonist Pk11195 can facilitate apoptosis in cholangiocarcinoma following chemotherapy and radiotherapy.
Radiographic progression in children with polyarticular juvenile rheumatoid arthritis: a pilot study
Authors: Tam Mason, A. M. Reed, A. M. Nelson, K. B. Thomas
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To assess disease progression on hand/wrist <i>x</i> rays from children with polyarticular juvenile rheumatoid arthritis. <b>Methods:</b> Initial and subsequent films of 13 white children (10 girls) were read blind by a paediatric radiologist for the presence of joint space narrowing (JSN), erosions, and relative carpal length (RCL). <b>Results:</b> One child had subcutaneous nodules; one (of 11) was rheumatoid factor positive; six were ANA positive. Median age at diagnosis was 10.7 years (2.5 to 15.9). Median number of involved joints (swelling, pain, or decreased range of motion) at diagnosis was 16 (6 to 33). Four initial <i>x</i> rays had either erosions or JSN. Subsequent <i>x</i> rays were done at (median) 13.3 (8.3 to 24.9) months after initial <i>x</i> rays. One of 10 subsequent <i>x</i> rays had shortened RCL, and six of 13 were worse than the initial ones. Four of these developed new erosions, one had increased number of erosions, and one developed new JSN. <b>Conclusions:</b> About half the children with polyarticular juvenile rheumatoid arthritis will have evidence of radiographic progression within two years after diagnosis. Thus newly diagnosed children are at high risk of substantial joint destruction and potential disability, emphasising the need for prompt treatment.
Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens
Authors: Pau Montesinos, Chelo Rayón, Edo Vellenga, Salut Brunet, José González, Marcos González, Aleksandra Holowiecka, Jordi Esteve, Juan Bergua, José D. González, Concha Rivas, Mar Tormo, Vicente Rubio, Javier Bueno, Félix Manso, Gustavo Milone, Javier de la Serna, Inmaculada Pérez, Manuel Pérez-Encinas, Isabel Krsnik, Josep M. Ribera, Lourdes Escoda, Bob Lowenberg, Miguel A. Sanz
Journal: Blood (2010)
Immune Cell Modulation of Cardiac Remodeling
Authors: Richard M. Mortensen
Journal: Circulation (2012)

H eart failure remains a critical target to improve the health of the US population.It is a major cause of morbidity and mortality in the United States. 1 Heart failure is a result of acute or chronic injury followed by healing and remodeling that are insufficient to maintain or restore function.Myocardial infarction (MI) is the major cause of heart dysfunction, but other more chronic injuries, such as those caused by hypertension or genetic defects have many similarities.
Preoperative Therapy in Invasive Breast Cancer: Pathologic Assessment and Systemic Therapy Issues in Operable Disease
Authors: Julie R. Gralow, Harold J. Burstein, William Wood, Gabriel N. Hortobagyi, Luca Gianni, Gunter von Minckwitz, Aman U. Buzdar, Ian E. Smith, William F. Symmans, Baljit Singh, Eric P. Winer
Journal: Journal of Clinical Oncology (2008)

To review the state of the science with respect to preoperative systemic therapy and pathologic assessment in operable breast cancer.This article reviews data presented at the National Cancer Institute State of the Science Conference on Preoperative Therapy in Invasive Breast Cancer as well as supporting published data.Preoperative chemotherapy in operable breast cancer has been shown to improve breast conservation rates as a result of tumor response to therapy. When patients are given preoperative systemic therapy, regimens should be the same as those established as safe and active in the adjuvant setting. At present, there are no data to suggest that systemic treatment should be tailored based on initial tumor response, or based on the extent of residual disease. In operable breast cancer, there seems to be no survival advantage from initiation of systemic therapy before surgery. A variety of clinical, imaging, and pathologic measurements are available to gauge tumor response to treatment. There is a clear correlation between tumor response in the breast and lymph nodes and both disease-free and overall survival. Pathologic complete response and other pathologic measures may be useful as surrogate end points in evaluating and understanding new therapies.In operable breast cancer, preoperative systemic therapy is effective and can improve breast conservation rates. Unless the tumor is large or the patient is in a clinical trial, postoperative adjuvant systemic therapy is the standard of care. To achieve optimal outcomes, preoperative systemic therapy must be administered as part of a coordinated, multimodality treatment program. The preoperative setting provides a unique opportunity to study the impact of systemic therapies on breast cancer biology.
Clinical validation of the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) II criteria in an open-access unit: a prospective study
Authors: A. Gimeno García, Y. González, E. Quintero, D. Nicolás-Pérez, Z. Adrián, R. Romero, O. Alarcón Fernández, M. Hernández, M. Carrillo, V. Felipe, J. Díaz, L. Ramos, M. Moreno, A. Jiménez-Sosa
Journal: Endoscopy (2011)

<b>Background and study aims:</b> The European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE I) criteria were recently updated (EPAGE II), but no prospective studies have used these criteria in clinical practice. The aim of the current study was to validate the EPAGE II criteria in an open-access endoscopy unit. <b>Patients and methods:</b> A prospective observational study was conducted in an open-access endoscopy unit at a tertiary care referral center. Consecutive outpatients (n = 1004; mean age 58.9 ± 13.1 years; 45 % men) were referred for diagnostic colonoscopy between September 2009 and February 2010. The appropriateness of colonoscopy was assessed based on EPAGE II criteria, and the relationship between appropriateness and both referral doctor and detection of significant lesions was examined. The effectiveness of EPAGE II criteria in assessing appropriateness was measured by means of sensitivity, specificity, and positive and negative predictive values for detecting significant lesions. <b>Results:</b> Colonoscopic cecal intubation was achieved in 956 patients (95.2 %). Most referral doctors were gastroenterologists (58.0 %) and the most common indication was colorectal cancer (CRC) screening (35.2 %). EPAGE II criteria were applicable in 968 patients (96.4 %); of these patients, the indication was appropriate in 778 (80.4 %), inappropriate in 102 (10.5 %), and uncertain in 88 (9.1 %). Patients with appropriate or uncertain indications based on EPAGE II criteria had more relevant endoscopic findings than those with inappropriate indications (38.8 % vs. 24.5 %; OR 1.95, 95 %CI 1.22 – 3.13; <i>P</i> < 0.005). Sensitivity and negative predictive value of EPAGE II criteria for detecting significant lesions were 93.1 % (95 %CI 90 % – 96 %) and 75.5 % (95 %CI 67 % – 84 %), respectively, whereas for advanced neoplastic lesions these values were 98.0 % (95 %CI 95 % – 100 %) and 98.0 % (95 % CI 95 % – 100 %), respectively. Adherence to EPAGE II recommendations was an independent predictor of finding a significant lesion (OR 1.93, 95 %CI 1.20 – 3.11; <i>P</i> = 0.007). <b>Conclusions:</b> EPAGE II is a simple, valid score for detecting inappropriate colonoscopies in clinical practice.
Integration of a Foreign Gene into a Native Complex Does Not Impair Fitness in an Experimental Model of Lateral Gene Transfer
Authors: S. Omer, A. Kovacs, Y. Mazor, U. Gophna
Journal: Molecular Biology and Evolution (2010)

Lateral gene transfer (LGT) is a central force in microbial evolution. The observation that genes encoding subunits of complexes exhibit relatively compatible phylogenies, suggesting vertical descent, can be explained by different evolutionary scenarios. On the one hand, the failure of a new gene product to correctly interact with preexisting protein subunits can make its acquisition neutral-a theory termed the "complexity hypothesis." On the other hand, foreign subunit-encoding genes may reduce the fitness of the new host by disrupting the stoichiometric balance between complex subunits, resulting in purifying selection against gene retention. We previously showed in a model LGT system that overexpression of an orthologous subunit was neutral due to lack of interaction with host subunits. Here, we examine a case where the foreign protein is more similar to its native orthologs, by expressing the RNA polymerase β subunit (RpoB) of Bacillus subtilis in Escherichia coli. The foreign subunit is shown by coimmunoprecipitation to interact with the host subunits, and to form novel, nonspecific interactions. Nevertheless, the host did not incur any fitness disadvantage, as measured by its growth. We conclude that LGT of complex subunits may be neutral even when the transferred subunit can integrate into the host complex and that this neutrality can be a fertile ground for selective forces once the environment changes.
N-Acetylcysteine In The Prevention Of Radiocontrast-Induced Nephropathy
Authors: Steven Fishbane, John H. Durham, Kevin Marzo, Michael Rudnick
Journal: Journal of the American Society of Nephrology (2004)

N-acetylcysteine is a remarkably active agent shown to be useful in a variety of clinical settings. The drug has actions relevant to radiocontrast-induced nephropathy (RCIN) that include vasodilatation, enhancement of renal medullary blood flow, and antioxidant properties. The drug's pharmacokinetics are remarkable for almost complete first pass metabolism after oral administration, resulting in no free drug reaching the circulation. After intravenous administration, extensive reaction with tissue and plasma proteins greatly limits the amount of circulating free drug. Given the difficulty achieving free drug in the systemic circulation, it is highly likely that the drug works via its metabolites. The primary mechanism may be through L-cysteine as a cellular source for glutathione production. Clinical studies of N-acetylcysteine in the prevention of RCIN have yielded highly mixed results; five were dramatically positive, and eight others had no demonstrable efficacy at all. The following will review the individual studies, attempt to reconcile the divergent results, and propose future research needs.