tbuckley/cabot-search huggingface dataset:
Analysis of T cell hybridomas. III. Distinctions between two types of hapten-specific suppressor factors that affect plaque-forming cell responses.
Authors: D H Sherr, M Minami, K Okuda, M E Dorf
Journal: The Journal of Experimental Medicine (1983)

The ability of two cloned T cell hybridomas and their products to specifically suppress the in vitro plaque-forming cell (PFC) response to the 4-hydroxy-3-nitrophenyl acetyl hapten (NP) was studied. Supernatant from one hybridoma (TS1) was shown to suppress in the induction but not the effector phase of the immune response. Supernatant from the TS1 hybridoma was capable of inducing second-order (TS2) effector-phase suppressor cells in vitro but did not suppress the response of anti-I-J plus C-treated responder cells. In contrast, supernatant from a second hybridoma (TS3) was capable of suppressing PFC responses when added either in the induction or the effector phase of the response. TS3 supernatant was unable to induce effector-phase suppressor cells but was capable of suppressing the response of anti-I-J plus C-treated responder cells. In addition, specific suppressor factors isolated from supernatants of the TS1 and TS3 hybridomas were shown to bind to NP, bear NPb idiotypic and I-J-encoded but not immunoglobulin-constant region determinants. The factor secreted by the TS3 hybridoma appears to act directly on B cell targets. Mild reduction of this factor results in two separable moieties, only one of which binds NP. Reconstitution experiments suggest that both chains are required for function. The collective data indicate that these hybridomas represent cells from first- and third-order suppressor T cell populations described previously in contact sensitivity and in vitro PFC systems. The implications of the ability of these hybridoma products to affect both T and B cell-mediated immune responses are discussed.
Riboflavin and Ultraviolet Light A Therapy as an Adjuvant Treatment for Medically Refractive Acanthamoeba Keratitis
Authors: Yasin A. Khan, Renata T. Kashiwabuchi, Suy Anne Martins, Juan M. Castro-Combs, Sachin Kalyani, Philip Stanley, David Flikier, Ashley Behrens
Journal: Ophthalmology (2010)
Cancer and insulin-like growth factor-I
Authors: G. D. Smith
Journal: BMJ (2000)

Insulin-like growth factor-I acts as an important mediator between growth hormone and growth throughout fetal and childhood development. Its effects and those of the other insulin-like growth factors are modulated by at least six different binding proteins. The role of insulin-like growth factor-I in promoting cancer has been investigated for many years, but recently the quality and quantity of evidence has increased.1 In particular, a number of prospective studies using stored blood collected up to 14 years before the onset of disease have shown associations between insulin-like growth factor-I and prostate cancer, premenopausal breast cancer, and colon cancer.2-4

The risk of cancer is higher among people with raised concentrations of insulin-like growth factor-I, and it is lower among those with high concentrations of insulin-like growth factor binding protein-3 (the main binding protein). The associations are similar when people whose blood samples were taken soon before diagnosis are excluded from analyses, suggesting that the observed relations are not due to the release of the growth factor by preclinical cancers.2-4 The effects are sizeable and stronger than the effects seen in relation to most previously reported risk factors.1 Weaker evidence from case-control studies suggests that the ratio of insulin-like growth factor-I to insulin-like growth factor binding protein-3 may …
An infant with respiratory distress and failure to thrive
Authors: F. Morini, D.A. Cozzi, A. Conforti, P. Capocaccia, A.M. Zicari, G. Tancredi, F. Midulla
Journal: European Respiratory Journal (2002)

A 4‐month-old male was referred to the Dept of Paediatric Surgery at the authors' institution, for the investigation of respiratory distress, failure to thrive and complete situs viscerum inversus since birth. A chest radiograph obtained a few hours after birth showed situs viscerum inversus, left apical atelectasis, hyperinflation and hyperlucency of the remaining left lung, and a mild shift of the mediastinum toward the right. The right lung was normal. The infant was born at term, after an uneventful pregnancy, by elective caesarean section. The parents were consanguineous and the baby had a positive maternal family history for situs viscerum inversus and chronic respiratory diseases.

On admission, the infant's general condition was poor, his body weight was 5.490 kg (5th percentile) and he was 62.5 cm in height (10th percentile). Clinical examination disclosed tachypnoea (70 breaths·min−1), chest retractions and barrel chest. The arterial oxygen saturation in room air was 90% when the child was awake, reaching 97% with 2 L·min−1 of oxygen. The cardiac frequency was 150 beats·min−1. On examination of the chest, auscultation revealed diffuse bilateral expiratory wheezing and right posterobasal crackles. The remainder of the examination was compatible with situs viscerum inversus and negative. Cardiac evaluation (electrocardiogram and echocardiogram) was compatible with dextrocardia. Arterial blood gas analysis at room air showed an arterial oxygen tension of 6.8 kPa (51 mmHg) and an arterial carbon dioxide tension of 5.7 kPa (43 mmHg). Red blood cells were found at a level of 5.05×1012·L−1, haemoglobin at 14 g·dL−1, white blood cells at 12.6×109 L−1 (neutrophils 37%, eosinophils 3%, basophils 2%, lymphocytes 51%, and monocytes 7%), and the erythrocyte sedimentation rate at the first hour was 13. C‐reactive protein, immune profile, blood chemistry, and sweat test were normal. Microbiological studies for common bacteria, Mycoplasma pneumoniae , Chlamidia trachomatis …
Weight loss and an abdominal mass after resection of a lung carcinoma
Authors: T Kiyokawa
Journal: Gut (2006)

A 47 year old man underwent a right upper lobectomy with resection of the chest wall for pleomorphic carcinoma of the lung in July 2003. In January 2004, he had abdominal pain and anorexia. Gastrointestinal endoscopy showed no …
Enhancement of Monocyte Procoagulant Activity by Adhesion on Vascular Smooth Muscle Cells and Intercellular Adhesion Molecule-1–Transfected Chinese Hamster Ovary Cells
Authors: Nikolaus Marx, Franz-Josef Neumann, Dietlind Zohlnhöfer, Timm Dickfeld, Almuth Fischer, Susanne Heimerl, Albert Schömig
Journal: Circulation (1998)

Background —Plaque erosion is a frequent finding in sudden death due to coronary thrombosis. The present study sought to investigate whether monocyte adhesion to human aortic vascular smooth muscle cells (VSMCs) induces procoagulant activity (PCA) and whether this could be mediated by intercellular adhesion molecule-1 (ICAM-1). Methods and Results —We incubated mononuclear cells (MNCs) with VSMCs and ICAM-1–transfected Chinese hamster ovary (CHO) cells, investigated monocyte tissue factor (TF) mRNA expression by Northern blot analysis and TF protein expression by ELISA, and measured PCA. Incubation of MNCs with VSMCs for 6 hours increased PCA from 0.7±0.1 to 166.0±37.9 mU/10 5 cells ( P =0.007), which could be inhibited in a dose-dependent manner by the addition of blocking anti–ICAM-1 monoclonal antibodies. Prestimulation of VSMCs with interleukin-1β enhanced surface ICAM-1 expression significantly but did not induce PCA in VSMCs. Incubation of MNCs with prestimulated VSMCs led to a further increase in PCA to 239.9±27.9 mU/10 5 cells ( P =0.02 compared with incubation with unstimulated VSMCs). Incubation of MNCs with VSMCs enhanced TF mRNA after 2 hours and significantly increased TF protein content after 6 hours. Incubation of purified monocytes with ICAM-1–transfected CHO cells increased PCA from 1.2±0.2 to 81.9±3.3 mU/10 5 cells ( P &lt;0.001 compared with incubation with untransfected CHO cells) after 6 hours. This effect could be inhibited significantly by the addition of blocking anti-CD18, anti-CD11b, or anti-CD11c monoclonal antibodies. Similar results were obtained for MNCs. Conclusions —Monocyte adhesion to VSMCs induces TF mRNA and protein expression and monocyte PCA, which is regulated by β 2 -integrin–mediated monocyte adhesion to ICAM-1 on VSMCs.
Disappearance of the Telomere Dysfunction-Induced Stress Response in Fully Senescent Cells
Authors: Christopher J. Bakkenist, Rachid Drissi, Jing Wu, Michael B. Kastan, Jeffrey S. Dome
Journal: Cancer Research (2004)

Abstract Replicative senescence is a natural barrier to cellular proliferation that is triggered by telomere erosion and dysfunction. Here, we demonstrate that ATM activation and H2AX-γ nuclear focus formation are sensitive markers of telomere dysfunction in primary human fibroblasts. Whereas the activated form of ATM and H2AX-γ foci were rarely observed in early-passage cells, they were readily detected in late-passage cells. The ectopic expression of telomerase in late-passage cells abrogated ATM activation and H2AX-γ focus formation, suggesting that these stress responses were the consequence of telomere dysfunction. ATM activation was induced in quiescent fibroblasts by inhibition of TRF2 binding to telomeres, indicating that telomere uncapping is sufficient to initiate the telomere signaling response; breakage of chromosomes with telomeric associations is not required for this activation. Although ATM activation and H2AX-γ foci were readily observed in late-passage cells, they disappeared once cells became fully senescent, indicating that constitutive signaling from dysfunctional telomeres is not required for the maintenance of senescence.
Clinical efficacy of infliximab plus methotrexate in DMARD naive and DMARD refractory rheumatoid arthritis is associated with decreased synovial expression of TNF and IL18 but not CXCL12
Authors: M van Oosterhout, E W N Levarht, J K Sont, T W J Huizinga, R E M Toes, J M van Laar
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Tumour necrosis α (TNFα) blocking agents lead to pronounced clinical effects and reduced synovial infiltrate in rheumatoid arthritis. Laboratory and clinical studies suggest that TNFα independent pathways play a role in the disease. <b>Objectives:</b> To evaluate the immunopathological effects of combination therapy on rheumatoid synovial tissue in order to identify TNFα independent mechanisms. <b>Methods:</b> 12 rheumatoid patients, including four DMARD (disease modifying antirheumatic drug) naive patients with early disease, were studied for the effect of combination therapy with infliximab and methotrexate on the synovial infiltrate. Biopsies and clinical assessments (DAS28) were carried out before the first and after the third infusion of infliximab. Synovial inflammation was scored semiquantitatively. Co-expression of CD38<sup>+</sup> cells was studied by an immunofluorescent double labelling technique. <b>Results:</b> Marked clinical responses were associated with a global reduction in the synovial infiltrate and expression of cytokines, notably interleukin 18 and TNFα, but low grade disease activity persisted. There was no effect on the expression of CXC chemokine ligand (CXCL12), and germinal centre-like structures were still detectable in synovial tissue in two patients after treatment. CD38<sup>+</sup> activated T cells were more resistant to treatment than CD38<sup>+</sup> plasma cells. No differences in clinical response or effects on synovial infiltrate were observed between DMARD refractory and DMARD naive patients. <b>Conclusions:</b> Persistent expression of CXCL12 and incomplete resolution of lymphocytic infiltrates after infliximab plus methotrexate indicates that TNFα independent mechanisms are operative in rheumatoid arthritis. This may contribute to low grade disease activity, even in DMARD naive patients with early disease.
THE NEURAL BASIS OF TEMPORAL PROCESSING
Authors: Michael D. Mauk, Dean V. Buonomano
Journal: Annual Review of Neuroscience (2004)

A complete understanding of sensory and motor processing requires characterization of how the nervous system processes time in the range of tens to hundreds of milliseconds (ms). Temporal processing on this scale is required for simple sensory problems, such as interval, duration, and motion discrimination, as well as complex forms of sensory processing, such as speech recognition. Timing is also required for a wide range of motor tasks from eyelid conditioning to playing the piano. Here we review the behavioral, electrophysiological, and theoretical literature on the neural basis of temporal processing. These data suggest that temporal processing is likely to be distributed among different structures, rather than relying on a centralized timing area, as has been suggested in internal clock models. We also discuss whether temporal processing relies on specialized neural mechanisms, which perform temporal computations independent of spatial ones. We suggest that, given the intricate link between temporal and spatial information in most sensory and motor tasks, timing and spatial processing are intrinsic properties of neural function, and specialized timing mechanisms such as delay lines, oscillators, or a spectrum of different time constants are not required. Rather temporal processing may rely on state-dependent changes in network dynamics.
Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 Diabetes
Authors: Andreas L. Birkenfeld, Gerald I. Shulman
Journal: Hepatology (2013)

Nonalcoholic fatty liver disease (NAFLD), hepatic insulin resistance, and type 2 diabetes are all strongly associated and are all reaching epidemic proportions. Whether there is a causal link between NAFLD and hepatic insulin resistance is controversial. This review will discuss recent studies in both humans and animal models of NAFLD that have implicated increases in hepatic diacylglycerol (DAG) content leading to activation of novel protein kinase Cϵ (PKCϵ) resulting in decreased insulin signaling in the pathogenesis of NAFLD-associated hepatic insulin resistance and type 2 diabetes. The DAG-PKCϵ hypothesis can explain the occurrence of hepatic insulin resistance observed in most cases of NAFLD associated with obesity, lipodystrophy, and type 2 diabetes.
Selective inhibition of syncytium-inducing and nonsyncytium-inducing HIV-1 variants in individuals receiving didanosine or zidovudine, respectively.
Authors: A B van't Wout, L J Ran, M D de Jong, M Bakker, R van Leeuwen, D W Notermans, A E Loeliger, F de Wolf, S A Danner, P Reiss, C A Boucher, J M Lange, H Schuitemaker
Journal: Journal of Clinical Investigation (1997)

By studying changes in the clonal composition of HIV-1 populations during the first weeks of zidovudine (ZDV) treatment before the development of ZDV resistance-conferring mutations, we demonstrated previously a selective inhibition of nonsyncytium-inducing (NSI) HIV-1, even when present as coexisting population in individuals also harboring syncytium-inducing (SI) HIV-1. In this study, we observed the opposite in individuals receiving didanosine (ddI) treatment. In these individuals (n = 7) a median -0.98 log change (range -1.55-0.08) in infectious cellular SI load was observed, whereas the coexisting NSI load was only minimally affected (median -0.15 log, range -1.27-0.50; P = 0.03). The virus phenotype-dependent treatment responses were independent of the clonal composition of HIV-1 populations at baseline. Individuals treated with a combination of ZDV and ddI revealed an equal decline of both NSI and SI infectious cellular load (n = 4; NSI: median -1.55 log, range -2.19 to -1.45; SI: median -1.47 log, range -1.81 to -0.86; P = 0.56). To test the hypothesis that the previously reported optimal activation of ZDV and ddI in activated and resting T cells, respectively, in combination with the differential T cell tropism of NSI and SI HIV-1 is the basis for the observed virus phenotype specific efficacy of nucleoside analogs, we studied the effect of treatment with a protease inhibitor that does not require intracellular activation. Individuals receiving ritonavir (n = 4) indeed showed equal declines in NSI and SI infectious cellular load (NSI: median -2.37 log, range -2.59 to -2.16; SI: median -2.82 log, range -3.14 to -2.50; P = 0.25). Our data suggest HIV-1 phenotype as an additional parameter in the design of optimal treatment regimens.
Evaluation of the Proteasome Inhibitor MLN9708 in Preclinical Models of Human Cancer
Authors: Erik Kupperman, Edmund C. Lee, Yueying Cao, Bret Bannerman, Michael Fitzgerald, Allison Berger, Jie Yu, Yu Yang, Paul Hales, Frank Bruzzese, Jane Liu, Jonathan Blank, Khristofer Garcia, Christopher Tsu, Larry Dick, Paul Fleming, Li Yu, Mark Manfredi, Mark Rolfe, Joe Bolen
Journal: Cancer Research (2010)

The proteasome was validated as an oncology target following the clinical success of VELCADE (bortezomib) for injection for the treatment of multiple myeloma and recurring mantle cell lymphoma. Consequently, several groups are pursuing the development of additional small-molecule proteasome inhibitors for both hematologic and solid tumor indications. Here, we describe MLN9708, a selective, orally bioavailable, second-generation proteasome inhibitor that is in phase I clinical development. MLN9708 has a shorter proteasome dissociation half-life and improved pharmacokinetics, pharmacodynamics, and antitumor activity compared with bortezomib. MLN9708 has a larger blood volume distribution at steady state, and analysis of 20S proteasome inhibition and markers of the unfolded protein response confirmed that MLN9708 has greater pharmacodynamic effects in tissues than bortezomib. MLN9708 showed activity in both solid tumor and hematologic preclinical xenograft models, and we found a correlation between greater pharmacodynamic responses and improved antitumor activity. Moreover, antitumor activity was shown via multiple dosing routes, including oral gavage. Taken together, these data support the clinical development of MLN9708 for both hematologic and solid tumor indications.
HTLV-1-negative pleomorphic T-cell lymphoma of the skin: the clinicopathological correlations and natural history of 15 patients
Authors: W. STERRY, A. SIEBEL, V. MIELKE
Journal: British Journal of Dermatology (1992)

The peripheral T-cell lymphomas represent a heterogeneous group and include, besides mycosis fungoides and Sézary syndrome, large-cell anaplastic lymphoma. We report 15 cases from our files that fulfil the histological criteria of pleomorphic T-cell lymphoma with primary skin involvement. Most of the cases were elderly with a male-to-female ratio of 1.5:1. The HTLV-1 serology was negative. The clinical features of these patients differed from those with mycosis fungoides and Sézary syndrome, in that eczematous and precursor lesions such as parapsoriasis en plaque were lacking apart from one exception. All the patients with small-cell pleomorphic T-cell lymphomas were alive, although three of the nine patients with medium-to-large tumour cells have died. Pleomorphic T-cell lymphoma should be regarded as a distinct entity among the lymphoproliferative disorders of the skin.
Frequent Alterations in the Expression of Serine/Threonine Kinases in Human Cancers
Authors: Maria Capra, Paolo Giovanni Nuciforo, Stefano Confalonieri, Micaela Quarto, Marco Bianchi, Manuela Nebuloni, Renzo Boldorini, Francesco Pallotti, Giuseppe Viale, Mikhail L. Gishizky, Giulio F. Draetta, Pier Paolo Di Fiore
Journal: Cancer Research (2006)

Abstract Protein kinases constitute a large family of regulatory enzymes involved in the homeostasis of virtually every cellular process. Subversion of protein kinases has been frequently implicated in malignant transformation. Within the family, serine/threonine kinases (STK) have received comparatively lesser attention, vis-a-vis tyrosine kinases, in terms of their involvement in human cancers. Here, we report a large-scale screening of 125 STK, selected to represent all major subgroups within the subfamily, on nine different types of tumors (∼200 patients), by using in situ hybridization on tissue microarrays. Twenty-one STK displayed altered levels of transcripts in tumors, frequently with a clear tumor type-specific dimension. We identified three patterns of alterations in tumors: (a) overexpression in the absence of expression in the normal tissues (10 kinases), (b) overexpression in the presence of expression by normal tissues (8 kinases), and (c) underexpression (3 kinases). Selected members of the three classes were subjected to in-depth analysis on larger case collections and showed significant correlations between their altered expression and biological and/or clinical variables. Our findings suggest that alteration in the expression of STK is a relatively frequent occurrence in human tumors. Among the overexpressed kinases, 10 were undetectable in normal controls and are therefore ideal candidates for further validation as potential targets of molecular cancer therapy. (Cancer Res 2006; 66(16): 8147-54)
Comparing Global Initiative for Asthma (GINA) criteria with the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT)
Authors: B.B. Koolen, M.W.H. Pijnenburg, H.J.L. Brackel, A.M. Landstra, N.J. van den Berg, P.J.F.M. Merkus, W.C.J. Hop, A.A.P.H. Vaessen-Verberne
Journal: European Respiratory Journal (2011)

Several tools are useful in detecting uncontrolled asthma in children. The aim of this study was to compare Global Initiative for Asthma (GINA) guidelines with the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) in detecting uncontrolled asthma in children. 145 children with asthma filled in a web-based daily diary card for 4 weeks on symptoms, use of rescue medication and limitations of activities, followed by either the C-ACT or ACT. For predicting uncontrolled asthma, score cut-off points of 19 were used for C-ACT and ACT. According to GINA guidelines, asthma was uncontrolled in 71 (51%) children and completely controlled in 19 (14%) children. The area under the curve in the receiver operating characteristic curves for C-ACT and ACT versus GINA guidelines were 0.89 and 0.92, respectively. Cut-off points of 19 for C-ACT and ACT resulted in a sensitivity of 33% and 66% in predicting uncontrolled asthma, respectively. C-ACT and ACT correlate well with GINA criteria in predicting uncontrolled asthma, but commonly used cut-off points for C-ACT and ACT seem to underestimate the proportion of children with uncontrolled asthma as defined by GINA.
Apple allergy across Europe: How allergen sensitization profiles determine the clinical expression of allergies to plant foods
Authors: Montserrat Fernández-Rivas, Suzanne Bolhaar, Eloina González-Mancebo, Riccardo Asero, Astrid van Leeuwen, Barbara Bohle, Yan Ma, Christof Ebner, Neil Rigby, Ana I. Sancho, Susan Miles, Laurian Zuidmeer, André Knulst, Heimo Breiteneder, Clare Mills, Karin Hoffmann-Sommergruber, Ronald van Ree
Journal: Journal of Allergy and Clinical Immunology (2006)
Hepatoerythropoietic porphyria precipitated by viral hepatitis.
Authors: R J Hift, P N Meissner, G Todd
Journal: Gut (1993)

Porphyria cutanea tarda (PCT), the condition resulting from a deficiency of hepatic uroporphyrinogen decarboxylase activity, is the commonest form of porphyria. Both acquired and familial form exist and are commonly associated in adults with liver disease and hepatic iron overload. The condition is extremely rare in children; most cases of childhood PCT are familial and some particularly severe cases have been shown to have a hepatoerythropoietic porphyria or homozygous uroporphyrinogen decarboxylase deficiency. A case is described of hepatoerythropoietic porphyria in which the disease was first precipitated at the age of two by a coincidental hepatitis A infection and improved as the hepatitis cleared. This paper reviews the evidence that viral hepatitis may precipitate overt PCT in children in a manner analogous to the precipitation of PCT in adults by alcohol associated liver disease.