tbuckley/cabot-search huggingface dataset:
Immunomodulation of the Lymphoresponsive Phases of Carcinogenesis: Mechanisms of Natural Immunity<xref ref-type="fn" rid="fn2">2</xref>
Authors: C H Evans, J A DiPaolo, J A Heinbaugh, A J DeMarinis
Journal: JNCI Journal of the National Cancer Institute (1982)

Biphasic modulation of the frequency of 3-methylcholanthrene-induced tumors in relation to increasing immunocompetence of tumor-bearing mice is indicative of lymphoresponsive stimulatory and inhibitory phases of carcinogenesis; components and mechanisms contributing to the paradoxical ability of the native or natural immune system to stimulate as well as to inhibit the development of cancer were identified with the use of an in vitro model of carcinogenesis. Normal NIH/N Syrian golden hamster spleen leukocytes caused a biphasic modulation of UV-irradiated hamster cell morphologic transformation that was dependent on the leukocyte-to-target cell (L:TC) ratio. Whereas low (less than 50:1) and high (greater than 200:1) L:TC ratios inhibited the transformation frequency, intermediate ratios were less inhibitory and seemingly immunostimulatory. Inhibition alone occurred with antigen- or mitogen-activated leukocytes or with macrophages. An anticarcinogenic lymphocyte hormone, lymphotoxin, eliminated the leukocyte-mediated stimulatory phase; galactose, a lymphotoxin inhibitor, blocked the leukocyte-mediated inhibitory phases. Thus immunoinhibition was mediated through lymphotoxin, and the apparent immunostimulation possibly resulted from immune cell regulation of lymphotoxin activity during the early stages of carcinogenesis.
Trastuzumab Activates Allogeneic or Autologous Antibody-Dependent Cellular Cytotoxicity against Malignant Rhabdoid Tumor Cells and Interleukin-2 Augments the Cytotoxicity
Authors: Yoshiki Katsumi, Yasumichi Kuwahara, Shinichi Tamura, Ken Kikuchi, Osamu Otabe, Kunihiko Tsuchiya, Tomoko Iehara, Hiroshi Kuroda, Hajime Hosoi, Tohru Sugimoto
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Malignant rhabdoid tumor (MRT) is an early childhood cancer with poor prognosis. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor-2 (HER-2), has been shown to be effective against breast cancer and other cancers. We investigated the effect of trastuzumab on MRT cell lines. Experimental Design: We examined expression of HER-2 on four MRT cell lines and two tumor tissues by indirect immunofluorescence, flow cytometry, and immunohistochemistry. The effect of trastuzumab against MRT cells was examined by cell growth assay. To observe the antibody-dependent cellular cytotoxicity of effector cells, we examined the cytotoxicity of trastuzumab in combination with allogeneic or autologous human peripheral blood mononuclear cells with and without IL-2 using the chromium release assay. Results: All four MRT cell lines and both MRT tissues expressed HER-2 protein. Trastuzumab alone did not reduce the viability of the MRT cell lines. On the other hand, the cytotoxicity of trastuzumab against each of the MRT cell lines was significantly increased by the presence of allogeneic and autologous peripheral blood mononuclear cells (P &amp;lt; 0.01). There was a strong correlation coefficient (r = 0.825) between HER-2 expression and the cytotoxicity enhanced by trastuzumab. Moreover, trastuzumab in combination with peripheral blood mononuclear cells augmented by interleukin-2 (IL-2) was significantly more cytotoxic than trastuzumab alone or IL-2 alone (P &amp;lt; 0.01). Conclusions: Our results indicate that (1) trastuzumab can exert antitumor effects on MRT cells by using the antibody-dependent cellular cytotoxicity of effector cells and (2) IL-2 can enhance the cytotoxicity of trastuzumab against MRT cells.
P-Cadherin Promotes Cell-Cell Adhesion and Counteracts Invasion in Human Melanoma
Authors: Veerle Van Marck, Christophe Stove, Karolien Van Den Bossche, Veronique Stove, Joana Paredes, Yves Vander Haeghen, Marc Bracke
Journal: Cancer Research (2005)

Malignant transformation of melanocytes frequently coincides with alterations in epithelial cadherin (E-cadherin) expression, switching on of neural cadherin (N-cadherin), and, when progressed to a metastatic stage, loss of membranous placental cadherin (P-cadherin). In vitro studies of melanoma cell lines have shown invasion suppressor and promoter roles for E-cadherin and N-cadherin, respectively. In the present study, we investigated the effect of P-cadherin on aggregation and invasion using melanoma cells retrovirally transduced with human P-cadherin. De novo expression of P-cadherin in P-cadherin-negative cell lines (BLM and HMB2) promoted cell-cell contacts and Ca2+-dependent cell-cell aggregation in two- and three-dimensional cultures, whereas it counteracted invasion. These effects were not observed following P-cadherin transduction of endogenously P-cadherin-positive MeWo cells. In addition, P-cadherin-transduced BLM cells coaggregated with keratinocytes and showed markedly reduced invasion in a reconstructed skin model. The proadhesive and anti-invasive effects of P-cadherin were abolished on targeted mutation of its intracellular juxtamembrane domain or its extracellular domain. For the latter mutation, we mimicked a known missense mutation in P-cadherin (R503H), which is associated with congenital hypotrichosis with juvenile macular dystrophy.
Apoptosis Control in Syncytia Induced by the HIV Type 1–Envelope Glycoprotein Complex
Authors: Karine F. Ferri, Etienne Jacotot, Julià Blanco, José A. Esté, Naoufal Zamzami, Santos A. Susin, Zhihua Xie, Greg Brothers, John C. Reed, Josef M. Penninger, Guido Kroemer
Journal: The Journal of Experimental Medicine (2000)

Syncytia arising from the fusion of cells expressing a lymphotropic HIV type 1–encoded envelope glycoprotein complex (Env) with cells expressing the CD4/CXC chemokine receptor 4 complex spontaneously undergo cell death. Here we show that this process is accompanied by caspase activation and signs of mitochondrial membrane permeabilization (MMP), including the release of intermembrane proteins such as cytochrome c (Cyt-c) and apoptosis-inducing factor (AIF) from mitochondria. In Env-induced syncytia, caspase inhibition did not suppress AIF- and Cyt-c translocation, yet it prevented all signs of nuclear apoptosis. Translocation of Bax to mitochondria led to MMP, which was inhibited by microinjected Bcl-2 protein or bcl-2 transfection. Bcl-2 also prevented the subsequent nuclear chromatin condensation and DNA fragmentation. The release of AIF occurred before that of Cyt-c and before caspase activation. Microinjection of AIF into syncytia sufficed to trigger rapid, caspase-independent Cyt-c release. Neutralization of endogenous AIF by injection of an antibody prevented all signs of spontaneous apoptosis occurring in syncytia, including the Cyt-c release and nuclear apoptosis. In contrast, Cyt-c neutralization only prevented nuclear apoptosis, and did not affect AIF release. Our results establish that the following molecular sequence governs apoptosis of Env-induced syncytia: Bax-mediated/Bcl-2–inhibited MMP → AIF release → Cyt-c release → caspase activation → nuclear apoptosis.
Cardiac Rehabilitation Use Among Veterans With Ischemic Heart Disease
Authors: David W. Schopfer, Steven Takemoto, Kelly Allsup, Christian D. Helfrich, P. Michael Ho, Daniel E. Forman, Mary A. Whooley
Journal: JAMA Internal Medicine (2014)

This study used VA inpatient files to determine the proportion of eligible veterans with ischemic heart disease who participated in cardiac rehabilitation (CR), whether the presence of an on-site CR program is associated with greater participation, and characteristics of the participants.
Colonic Lymphoid Nodular Hyperplasia in Children: Relationship to Food Hypersensitivity
Authors: Giuseppe Iacono, Alberto Ravelli, Lidia Di Prima, Calogero Scalici, Stefania Bolognini, Sara Chiappa, Giuseppe Pirrone, Giuseppina Licastri, Antonio Carroccio
Journal: Clinical Gastroenterology and Hepatology (2007)
U.S. Cancer Mortality: Nonwhite Predominance
Authors: Fred Burbank, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1972)

Study of cancer mortality trends in the United States re.,ealed an increasing nonwhite-to-white ratio of age-adjusted death rates. Non-white predominance began in 1950 for females and in 1956 for males. In females the shift resulted from a decline in death rates among whites, as rates for nonwhites remained unchanged, and in males from rates which rose over time in both races, but more rapidly in nonwhites. Each cancer site is analyzed with respect to its race differential and change in nonwhite mortality. The shift to nonwhite predominance in cancer mortality is probably due to many factors, but parallel trends in cancer incidence suggest that nonwhites are more exposed or vulnerable than whites to carcinogenic factors.
Comparative analyses of speech and language converge on birds
Authors: Gabriël J L Beckers, Robert C Berwick, Johan J Bolhuis
Journal: Behavioral and Brain Sciences (2014)

Abstract Unlike nonhuman primates, thousands of bird species have articulatory capabilities that equal or surpass those of humans, and they develop their vocalizations through vocal imitation in a way that is very similar to how human infants learn to speak. An understanding of how speech mechanisms have evolved is therefore unlikely to yield key insights into how the human brain is special.
Shear stress-induced up-regulation of the intermediate-conductance Ca2+-activated K+ channel in human endothelium
Authors: S Brakemeier
Journal: Cardiovascular Research (2003)

Objective: Wall shear stress associated with blood flow is a major stimuli for generation of endothelial vasodilating and antithrombotic factors and it also regulates endothelial gene expression.Activation of endothelial intermediate-conductance Ca 2 + -activated K + channels (IK Ca ) is important for the control of endothelial function by inducing cell hyperpolarization and thus generation of the endothelium-derived hyperpolarizing factor.In the present study we tested whether the IK Ca encoding IKCa1 gene is regulated by laminar shear stress (LSS).Methods: Human umbilical vein endothelial cells (HUVEC) were subjected to LSS with a magnitude of 0.5 -15 dyn/cm 2 and time intervals of 2 -24 h in a flow cone apparatus.Expression of the IKCa1 gene and IK Ca -functions were determined by using real time RT-PCR and patch-clamp techniques.Results: A short 2 -4 h-or long 24 h-exposure to a LSS with a low (venous) magnitude of 0.5 dyn/cm 2 had no effect on IKCa1 expression levels.An exposure for 2 and 4 h to LSS with an intermediate magnitude of 5 dyn/cm 2 was also ineffective, whereas an exposure for 24 h induced a significant threefold up-regulation of IKCa1 expression levels.An exposure to LSS with a higher (arterial) magnitude of 15 dyn/cm 2 , resulted in an eightfold up-regulation of IKCa1 expression levels after a 4 h-exposure and a fourfold increase of IKCa1 expression levels at 24 h.The increased IKCa1 expression levels following exposure to high levels of LSS resulted in enhanced IK Ca whole-cell currents and in an increased hyperpolarization of the endothelium in response to ATP and the IK Ca opener 1-EBIO.Inhibition of the mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK) kinase 1/2 (MEK/ERK) pathway by PD98059 prevented the LSS-induced up-regulation of IKCa1 expression levels and IK Ca whole-cell currents indicating that augmentation of IKCa1 expression levels is mediated by the LSS-induced activation of the MEK/ERK pathway.Conclusion: Long term exposure to LSS upregulates expression and function of endothelial IK Ca .This increase might represent a new important mechanism in endothelial adaptation to altered hemodynamics.
A breath test for malignant mesothelioma using an electronic nose
Authors: Eleanor A. Chapman, Paul S. Thomas, Emily Stone, Craig Lewis, Deborah H. Yates
Journal: European Respiratory Journal (2011)

Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity. 20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case–control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction. 10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases. Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.
Multiagent Concurrent Chemoradiotherapy for Locoregionally Advanced Squamous Cell Head and Neck Cancer: Mature Results From a Single Institution
Authors: David J. Adelstein, Jerrold P. Saxton, Lisa A. Rybicki, Ramon M. Esclamado, Benjamin G. Wood, Marshall Strome, Pierre Lavertu, Robert R. Lorenz, Marjorie A. Carroll
Journal: Journal of Clinical Oncology (2006)

A retrospective review with long-term follow-up is reported from the Cleveland Clinic Foundation studying radiation and concurrent multiagent chemotherapy in patients with locoregionally advanced squamous cell head and neck cancer.Between 1989 and 2002, 222 patients were treated with 4-day continuous infusions of fluorouracil (1,000 mg/m2/d) and cisplatin (20 mg/m2/d) during weeks 1 and 4 of either once daily or twice daily radiation therapy. Primary site resection was reserved for patients with residual or recurrent primary site disease after chemoradiotherapy. Neck dissection was considered for patients with N2 or greater disease, irrespective of clinical response, and for patients with residual or recurrent neck disease.With a median follow-up of 73 months, the Kaplan-Meier 5-year projected overall survival rate is 65.7%, freedom from recurrence rate is 74.0%, local control without the need for surgical resection rate is 86.7%, and overall survival rate with organ preservation is 62.2%. Including patients undergoing primary site resection as salvage therapy, the overall local control rate is 92.4%. Regional control rate at 5 years is 92.4%. Among patients with N2-3 disease, regional control was significantly better if a planned neck dissection was performed. Distant control at 5 years was achieved in 85.4% of patients and was significantly worse in patients with hypopharyngeal primary sites and patients with poorly differentiated tumors.Concurrent multiagent chemoradiotherapy can result in organ preservation and cure in the majority of appropriately selected patients with locoregionally advanced, nonmetastatic, squamous cell head and neck cancer. Distant metastatic disease was the most common cause of treatment failure. Late functional outcomes will require further investigation.
Hapten-specific delayed hypersensitivity to epsilon-2,4-dinitrophenyl-L-lysine-Ficoll in guinea pigs immunized with 2,4-dinitrophenyl-keyhole limpet hemocyanin.
Authors: P R McMaster, J D Owens, H F Dvorak, R Weichbrod, R Asofsky
Journal: The Journal of Experimental Medicine (1977)

After active immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), 2,4-dinitropheynl-L-lysine (DNPL)-Ficoll may elicit indurated, erythematous skin reactions lasting 24-72 h. Histological sections of these reactions, examined by microscope techniques, showed they contained polymorphonuclear leukocytes and perivascularly situated lymphocytes and macrophages, but had very few basophils. Consequently, the reaction was interpreted as having an immediate component and a component typical of delayed hypersensitivity; this indicated that the delayed reaction could be specific for the DNP hapten. Although this delayed type of skin reaction was not transferred to recipients with anti-DNP-KLH serum, one pool of that serum did sensitize guinea pigs so that they could respond with a different skin reaction after challenge with DNPL-Ficoll. This reaction was soft, pale pink, and lasted for 24 h. Histologically, it contained only a few polymorphonuclear leukocytes. It differed from the delayed reaction in actively immunized animals in that it lacked induration, and was devoid of lymphocytes and macrophages.
Sport and exercise medicine in undergraduate medical schools in the United Kingdom and Ireland
Authors: M Cullen, O Mcnally, S O Neill, D Macauley
Journal: British Journal of Sports Medicine (2000)

The formation of the Intercollegiate Academic Board in Sport and Exercise Medicine represents the first step towards recognition of sport and exercise medicine as an individual specialty, with its own higher specialist training programmes, leading to the establishment of sport and exercise medicine departments within the NHS. However, sports medicine is not an exclusively postgraduate activity and there is increasing interest among medical students. The opportunity for students to direct their own learning goals is in keeping with changes to undergraduate medical education suggested by the General Medical Council (GMC) in their paper entitled Tomorrows' doctors .1 One of their recommendations was to supplement the core curriculum with “special study modules”, offering students the opportunity to study, in depth, areas of particular interest. This “new” undergraduate curriculum was introduced into medical schools in the academic year 1997/1998.

Our aim was to study the level of interest in the teaching of sport and exercise medicine in undergraduate medical schools, with specific objectives to record the proportion of schools with formal and informal teaching of sport and exercise medicine, the extent of teaching, and in what context it was taught.

This was a questionnaire study of medical schools in the United Kingdom and Ireland. The first draft of the questionnaire was drawn up by the authors. It was appraised for content …
Metabolism of Tac (IL2Ralpha): physiology of cell surface shedding and renal catabolism, and suppression of catabolism by antibody binding.
Authors: R P Junghans, T A Waldmann
Journal: The Journal of Experimental Medicine (1996)

The interleukin 2 receptor alpha (IL2Ralpha; CD25; Tac) is the prototypic model for soluble receptor studies. It exists in vivo as a transmembrane complete molecule (TM-Tac) on cell surfaces and as a truncated soluble form (sTac; sIL2R alpha). sTac has been used as a serum marker of T cell activation in immune disorders and of tumor burden in Tac-expressing malignancies. In vivo, serum levels of all soluble proteins depend on the balance between production and catabolism, but little is known about the metabolic features of this class of molecules. We have developed a model for Tac metabolism that incorporates new insights in its production and catabolism. Tac was shed from the surface of malignant and activated human T cells with a model half-life (t1/2) of 2-6h, but which was prolonged under certain circumstances. The rate of shedding is first order overall and nonsaturable over a two order of magnitude range of substrate (TM-Tac) expression. Once shed from cells Tac is subject to catabolic activities in the host. In vivo studies in mice showed that 90% of Tac was catabolized by the kidney with a t1/2 of 1 h and a filtration fraction of 0.11 relative to creatinine. The remaining 10% of catabolism was mediated by other tissues with a t1/2 of 10 h. Approximately 1-3% of sTac is excreted intact as proteinuria with the remaining 97-99% catabolized to amino acids. Antibody to the receptor induced a marked delay in sTac catabolism by preventing filtration of the smaller protein through the renal glomerulus and additionally suppressing other nonrenal catabolic mechanisms. A discrepancy between the catabolic rats for Tac and anti-Tac in the same complex was interpreted as a previously unrecognized differential catabolic mechanism, suggesting features of the Brambell hypothesis and immunoglobulin G transport and catabolism, in which the antigen-in-complex in intracellular vesicles is relatively less protected from catabolism than the associated antibody. In light of the pivotal role played by the kidney in sTac catabolism and the impact of administered antibody, the serum concentration of Tac in the settings of renal dysfunction or antibody therapy is not a suitable surrogate of activated T cells or of the body burden of tumor. These results provide parameters for assessing soluble receptor-ligand interactions generally.
Validity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) in patients with early spondyloarthritis from the Esperanza programme
Authors: C Fernández-Espartero, E de Miguel, E Loza, E Tomero, M Gobbo, M A Descalzo, E Collantes-Estévez, J Mulero, S Muñoz-Fernández, P Zarco, L Carmona
Journal: Annals of the Rheumatic Diseases (2013)

To evaluate the validity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) in early spondyloarthritis (SpA) in comparison with conventional clinical measures of disease activity.Six hundred and seventy-six incident cases of early SpA from the Esperanza programme were included. Patients were categorised into high and low disease activity states based on patient and physician global assessment scores and on the physician's decision to start treatment with a disease-modifying antirheumatic drug or tumour necrosis factor blocker. The discriminant ability of ASDAS-C-reactive protein (CRP) and ASDAS-erythrocyte sedimentation rate (ESR) was tested using standardised mean differences between patients with high and low disease activity. Convergent validity was tested by Pearson correlation between ASDAS versions and other measures of disease activity.ASDAS-ESR and ASDAS-CRP showed good correlation with BASDAI (r=0.79 and 0.74, respectively). Both indices correlated well with the patient global assessment (r=0.70 in both indices) and moderately with the physician global score (r=0.46 and 0.47, respectively). CRP and ESR showed poor correlation with patient- and physician-derived measures. ASDAS performed similarly across the global SpA sample, ankylosing spondylitis (AS), non-radiographic axial SpA and peripheral SpA.ASDAS performed as a valid activity score even being slightly better than the Bath Ankylosing Spondylitis Disease Activity Index in its ability to discriminate between high and low disease activity in early SpA. ASDAS performed similarly in AS, early forms of SpA, non-radiographic axial SpA and peripheral SpA.