tbuckley/cabot-search huggingface dataset:
An Array-Based Approach to Determine Different Subtype and Differentiation of Non-Small Cell Lung Cancer
Authors: Chao Li, Yucai Yang, Luming Wei, Xiaoying Wang, Zhaoxia Wang, Yongmei Yin, Genxi Li
Journal: Theranostics (2014)

Simple and accurate methods of discriminating subtype or differentiation of human tumor are critical for designing treatment strategies and predicting disease prognosis, and the currently used method to determine the two important factors mainly depends on histological examination by microscopy observation, which is laborious, highly trained operator required, and prone to be disruptive due to individual-to-individual judgment.Here we report a novel array-based method based on the interaction of graphene oxide (GO) and single-strand DNA modified gold nanoparticles (ssDNA-AuNPs) to distinguish between different subtypes and grades of tumors through their overall intracellular proteome signatures.Strategically, we first select eight proteins at 0.5 nM concentration in buffer or 10 nM in human serum to verify the discriminant ability of our method, then choose adenocarcinoma and squamous-cell carcinoma that account for 90% non-small cell lung cancer, as well as their respective three tumor grades as model system to provide a realistic testing ground for clinical cancer analysis.Consequently, total differentiation between different subtype and grade of tumor tissues has been achieved with as little as 100 ng of intracellular protein, suggesting the high sensitivity and selectivity of this sensor array.Overall, this array-based approach may provide the possibility for unbiased and simplified personalized tumor classification diagnostics in the future.
The specificity of rejection and the absence of susceptibility of pancreatic islet beta cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat.
Authors: R Sutton, D W Gray, P McShane, M J Dallman, P J Morris
Journal: The Journal of Experimental Medicine (1989)

The specificity of rejection of isolated pancreatic islets was examined in the rat using a quantitative model in which syngeneic (DA) or a mixture of syngeneic and allogeneic (DA and LEW or PVG) islets were implanted beneath the capsule of the kidney of nondiabetic normal rats (DA). 3 wk after transplantation total insulin extraction assays of the kidney with its islet implant together with immunohistological examination of the site of transplantation for evidence of syngeneic or allogeneic tissue demonstrated the total destruction of allogeneic islets without any evidence of damage to syngeneic islets either distant or in immediate proximity to allogeneic islets. Pancreatic islets, and especially beta cells, appear to be particularly vulnerable to the effector arm of both autoimmune and alloimmune responses, a vulnerability that has been attributed to the cytotoxic effects of lymphokines, notably IL-1, released in both autoimmune and alloimmune responses. The experiments reported here demonstrate not only the exquisite specificity of the allograft reaction but are not compatible with a hypothesis that B cells within an intact islet are nonspecifically susceptible to destruction by lymphokines.
Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response
Authors: Anna I. Markowska, Fu-Tong Liu, Noorjahan Panjwani
Journal: The Journal of Experimental Medicine (2010)

Recent studies have shown that a carbohydrate-binding protein, galectin-3, is a novel pro-angiogenic molecule. The mechanism by which galectin-3 promotes angiogenesis remains unknown. We demonstrate here that galectin-3 is a mediator of vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-mediated angiogenic response. Angiogenesis assays revealed that galectin-3 inhibitors, β-lactose and dominant-negative galectin-3, reduce VEGF- and bFGF-mediated angiogenesis in vitro and that VEGF- and bFGF-mediated angiogenic response is reduced in galectin-3 knockdown cells and Gal3−/− animals. Integrin αvβ3 was identified as the major galectin-3–binding protein and anti-αv, -β3, and -αvβ3 integrin function-blocking antibodies significantly inhibited the galectin-3–induced angiogenesis. Furthermore, galectin-3 promoted the clustering of integrin αvβ3 and activated focal adhesion kinase. Knockdown of GnTV, an enzyme that synthesizes high-affinity glycan ligands for galectin-3, substantially reduced: (a) complex N-glycans on αvβ3 integrins and (b) VEGF- and bFGF-mediated angiogenesis. Collectively, these data suggest that galectin-3 modulates VEGF- and bFGF-mediated angiogenesis by binding via its carbohydrate recognition domain, to the GnTV synthesized N-glycans of integrin αvβ3, and subsequently activating the signaling pathways that promote the growth of new blood vessels. These findings have broad implications for developing novel, carbohydrate-based therapeutic agents for inhibition of angiogenesis.
SEROLOGICAL REACTIONS WITH A VIRUS CAUSING RABBIT PAPILLOMAS WHICH BECOME CANCEROUS
Authors: John G. Kidd, J. W. Beard, Peyton Rous
Journal: The Journal of Experimental Medicine (1936)

The serum of a rabbit with large cancers resulting from the transplantation of a squamous cell carcinoma that had arisen from a virusinduced papilloma, possessed the power to neutralize the virus, and so too in less degree did that of an animal of the same transplantation series in which a small nodule had developed. The sera of rabbits carrying tar papillomas or the Brown-Pearce carcinoma proved wholly devoid of effect on the virus. The implantation of Brown-Pearce tumor material mixed with virus did not lead to an enduring establishment of the latter in the resulting growths, nor to any immediate changes in their morphological character. The significance of the facts is discussed.
The Cambridge Medical Ethics Workbook: Case Studies, Commentaries and Activities
Authors: Tony Lopez
Journal: Journal of the Royal Society of Medicine (2001)

Our clinical practice is steered by ethical principles. They guide the decisions we make in our clinics and ward rounds; what we tell our patients, and what we omit to tell them; the research we do. Medical ethics and law are now part of the core curriculum for medicine. The Cambridge Medical Ethics Workbook sets out to be both a textbook and a work of reference. In reviewing it, my plan was to dip in and out, reading subjects that took my interest. For me a book that did not provide a rewarding self-contained read over a cup of tea was likely to remain on the shelf.
Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats.
Authors: Y Ogawa, H Masuzaki, N Isse, T Okazaki, K Mori, M Shigemoto, N Satoh, N Tamura, K Hosoda, Y Yoshimasa
Journal: Journal of Clinical Investigation (1995)

The obese (ob) gene has recently been isolated through a positional cloning approach, the mutation of which causes a marked hereditary obesity and diabetes mellitus in mice. In the present study, we isolated rat ob cDNA and examined the tissue distribution of the ob gene expression in rats. We also studied the gene expression in genetically obese Zucker fatty (fa/fa) rats. The rat ob gene product, a 167 amino acid protein with a putative signal sequence, was 96 and 83% homologous to the mouse and human ob proteins, respectively. Northern blot analysis using the rat ob cDNA probe identified a single mRNA species of 4.5 kb in size in the adipose tissue, while no significant amount of ob mRNA was present in other tissues in rats. The ob gene was expressed in the adipose tissue with region specificities. The rank order of the ob mRNA level in the adipose tissue was epididymal, retroperitoneal, and pericardial white adipose tissue > mesenteric and subcutaneous white adipose tissue > or = interscapular brown adipose tissue. The ob gene expression occurred in mature adipocytes rather than in stromalvascular cells isolated from the rat adipose tissue. Expression of the ob gene was markedly augmented in all the adipose tissue examined in Zucker fatty (fa/fa) rats at the stage of established obesity. The present study leads to the better understanding of the physiologic and pathophysiologic roles of the ob gene.
Kv1.5 Is an Important Component of Repolarizing K <sup>+</sup> Current in Canine Atrial Myocytes
Authors: David Fedida, Jodene Eldstrom, J. Christian Hesketh, Michelle Lamorgese, Laurie Castel, David F. Steele, David R. Van Wagoner
Journal: Circulation Research (2003)

Although the canine atrium has proven useful in several experimental models of atrial fibrillation and for studying the effects of rapid atrial pacing on atrial electrical remodeling, it may not fully represent the human condition because of reported differences in functional ionic currents and ion channel subunit expression. In this study, we reassessed the molecular components underlying one current, the ultrarapid delayed rectifier current in canine atrium [ I Kur(d) ], by evaluating the mRNA, protein, immunofluorescence, and currents of the candidate channels. Using reverse transcriptase-polymerase chain reaction, we found that Kv1.5 mRNA was expressed in canine atrium whereas message for Kv3.1 was not detected. Western analysis on cytosolic and membrane fractions of canine tissues, using selective antibodies, showed that Kv3.1 was only detectable in the brain preparations, whereas Kv1.5 was expressed at high levels in both atrial and ventricular membrane fractions. Confocal imaging performed on isolated canine atrial myocytes clearly demonstrated the presence of Kv1.5 immunostaining, whereas that of Kv3.1 was equivocal. Voltage- and current-clamp studies showed that 0.5 mmol/L tetraethylammonium had variable effects on sustained K + currents, whereas a compound with demonstrated selectivity for hKv1.5 versus Kv3.1, hERG or the sodium channel, fully suppressed canine atrial I Kur tail currents and depressed sustained outward K + current. This agent also increased action potential plateau potentials and action potential duration at 20% and 50% repolarization. These results suggest that in canine atria, as in other species including human, Kv1.5 protein is highly expressed and contributes to I Kur .
Exhaled nitric oxide measurements: clinical application and interpretation
Authors: D R Taylor, M W Pijnenburg, A D Smith, J C D Jongste
Journal: Thorax (2006)

The use of exhaled nitric oxide measurements (F<sub>E</sub>no) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, F<sub>E</sub>no is a good surrogate marker for eosinophilic airway inflammation. High F<sub>E</sub>no levels may be used to distinguish eosinophilic from non-eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non-specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that F<sub>E</sub>no measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. F<sub>E</sub>no measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of F<sub>E</sub>no in preschool children and the use of reference values versus individual F<sub>E</sub>no profiles in managing patients with difficult or severe asthma.
Psoriatic arthritis: clinical subgroups and histocompatibility antigens.
Authors: N J McHugh, M R Laurent, B L Treadwell, J M Tweed, J Dagger
Journal: Annals of the Rheumatic Diseases (1987)

Histocompatibility antigens were determined in 60 patients with psoriatic arthritis. The patients were divided into clinical subgroups according to axial or peripheral joint involvement, disease severity based on number of peripheral joints involved, and the presence or absence of bone erosions. The total group showed a significant increase in frequency of HLA-A1, B17, B27, and DR7 when compared with a control population. The subgroup with spondylitis had a significant increase in frequency of HLA-B27 when compared with patients with peripheral arthritis (p less than 0.001). The subgroup with peripheral arthritis alone had a higher frequency of HLA-DR7 than the control group (p less than 0.001). There were also significant associations between HLA-DR7 and chronic severe disease (p less than 0.001) and between HLA-DR4 and the presence of erosions (p less than 0.05).
Expression of a class II major histocompatibility complex (MHC) heterodimer in a lipid-linked form with enhanced peptide/soluble MHC complex formation at low pH.
Authors: D A Wettstein, J J Boniface, P A Reay, H Schild, M M Davis
Journal: The Journal of Experimental Medicine (1991)

A murine class II major histocompatibility complex (MHC) heterodimer, Ek, expressed as a glycan-phosphatidyl inositol-anchored chimera on Chinese Hamster Ovary cells, can present peptides, but not processed antigen to T cells. This chimeric MHC requires a 100-times higher peptide concentration to achieve a two- to four-times lower level of T cell stimulation. Cleavage with phosphatidylinositol-specific phospholipase C and purification result in large quantities of heterodimer in a water-soluble form. Plates coated with this material and then incubated with peptide can efficiently stimulate the appropriate T cell hybridomas. This stimulation is significantly enhanced when peptides are preincubated with the plate-bound MHC molecules in a pH range (5.0-5.5) similar to that of late endosomes. More than half of the soluble Ek molecules can form a specific complex with cytochrome c peptides in this pH range. This suggests that class II MHC molecules undergo distinct conformational changes in endosomal compartments that render them more capable of forming functional complexes with peptide antigens, irrespective of other cell components.
Serum-Red Cell Interactions at Low Ionic Strength: Erythrocyte Complement Coating and Hemolysis of Paroxysmal Nocturnal Hemoglobinuria Cells*
Authors: David E. Jenkins, Robert C. Hartmann, Albert L. Kerns
Journal: Journal of Clinical Investigation (1967)

Complement coating and hemolysis were observed when erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) were incubated in isotonic sucrose solution in the presence of small amounts of serum. Normal cells were likewise coated with complement components but did not hemolyze. Both normal and PNH erythrocytes reduced the hemolytic complement activity of the serum used in this reaction. Experience with other simple saccharides and related compounds suggests that the low ionic strength of the sucrose solution is the feature that permitted complement coating of red cells and hemolysis of PNH erythrocytes. Isotonic solutions of other sugars or sugar alcohols that do not readily enter human erythrocytes could be substituted for sucrose. The mechanism for these reactions may possibly relate to the agglutination observed with erythrocytes tested in the serum-sucrose system. Even though PNH hemolytic activity could be removed by prior heating of serum or barium sulfate treatment of plasma, the agglutination phenomenon still persisted. The in vitro conditions necessary for optimal sucrose hemolysis of PNH erythrocytes were described and compared with those of the classical acid hemolysis test. The requirement for less serum in the sucrose hemolysis system than needed in the standard acid hemolysis reaction makes certain experiments, especially those using large amounts of autologous PNH serum, much more feasible. Additional advantages of the sucrose hemolysis test are that it can be carried out at room temperature in the presence of oxalate and citrate and that critical pH control is not essential. To date, the sucrose hemolysis test has been a sensitive and specific one for PNH. A modified test used for screening purposes, the "sugar water" test, is very easy to perform.
Autologous rosette-forming T cells as the responding cells in human autologous mixed-lymphocyte reaction.
Authors: R Palacios, L Llorente, D Alarcón-Segovia, A Ruíz-Arguelles, E Díaz-Jouanen
Journal: Journal of Clinical Investigation (1980)

Autologous rosette-forming cells (Tar cells) have surface and functional characteristics of post-thymic precursors and among these characteristics there are some that have been identified in the responsive cell of the autologous mixed-lymphocyte reaction (AMLR). We therefore did AMLR with circulating mononuclear cells from normal subjects using as responding cells either total T cells, T cells depleted of Tar cells, or purified Tar cells. The response of Tar cells in AMLR was significantly greater than that of total T cells and these responded significantly more than Tar-depleted T cells. Conversely, Tar cells responded less than total T cells or T cells depleted of Tar cells in allogeneic mixed-lymphocyte reactions. Increasing numbers of Tar cells gave significantly greater AMLR responses both alone and when added to diminishing proportions of Tar-depleted T cells to keep the number of T cells constant in the system. Tar cells are the responding cells in AMLR but not in allogeneic mixed-lymphocyte reactions.
Exogenous substrate preference of the post-ischaemic myocardium
Authors: D A G MICKLE, P J DEL NIDO, G J WILSON, R D HARDING, A D ROMASCHIN
Journal: Cardiovascular Research (1986)

Myocardial exogenous substrate preference was studied under conditions of increased plasma lactate concentration before and after a severe (halving of tissue ATP concentration, sixfold increase in tissue lactate concentration) but reversible (less than 1% necrosis on reperfusion) global ischaemic stress produced by continuous hypothermic electromechanical arrest of the heart of four hours' duration by aortic cross clamping and multidose potassium cardioplegia. Fatty acid oxidation was studied using 1-14C-palmitate under steady state conditions and under similar isovolumic fixed pressure conditions with the heart at a constant rate using a left ventricular intracavitary balloon. Exogenous free fatty acid oxidation during the pre-ischaemic period with an increased lactate concentration (3.9-5.8 mmol . litre-1) was 0.62(0.21) mumol . min-1 X 100 g-1 (mean (SEM)). This represented a mean of 32% of the total carbon dioxide produced in contrast to a post-ischaemia free fatty oxidation rate of 2.67(0.87) mumol . min-1 X 100 g-1, in the presence of even further increased plasma lactate concentrations (8.47-11.17 mmol . litre-1), representing a mean of 82% of the total carbon dioxide output. These data suggest that the substrate preference of the myocardium, under conditions of increased plasma lactate concentration, shifts to greater oxidation of exogenous free fatty acids after ischaemic stress.
HLA-A2 mutants immunoselected in vitro. Definition of residues contributing to an HLA-A2-specific serological determinant.
Authors: M S Krangel, S Taketani, D Pious, J L Strominger
Journal: The Journal of Experimental Medicine (1983)

The HLA-A2-specific mouse monoclonal antibody BB7.2 plus complement has been used to immunoselect variant clones of the lymphoblastoid cell line T5-1 (HLA-A1, -A2, -B8, and -B27). Members of one class of variant clones appear to express cell surface HLA-A2 molecules that display reduced reactivity with the selecting antibody, but normal or near normal reactivities with some other HLA-A2-specific monoclonal antibodies and human alloantisera. The HLA-A2 heavy chains derived from two of these variant clones were characterized by comparative double-label tryptic peptide mapping in conjunction with microsequence analysis. These heavy chains were found to carry distinct mutations in the same peptide in the molecule. We conclude that residues within this short segment of the polypeptide contribute to an HLA-A2-specific serological determinant.
Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms
Authors: D N R Payne
Journal: Thorax (2004)

The effective management and development of new treatments for children with difficult asthma requires investigation of the underlying airway pathology and its relationships with persistent symptoms and airflow limitation.The density of immunologically distinct inflammatory cells and cells expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin-embedded endobronchial biopsy specimens from 27 children with difficult asthma (6-16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic children (7-16 years) acted as controls. Reticular basement membrane (RBM) thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only.RBM thickness was greater in the asthmatic than the control group (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other significant tissue difference was seen, nor was there a difference between asthmatic subjects with daily symptoms after systemic corticosteroids and those who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80% predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027). Analysing all asthmatic subjects together, there were negative correlations between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI -0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI -0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO) and inflammatory cells of any type.In children with difficult asthma treated with systemic corticosteroids, persistent airflow limitation is associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy specimens.
BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study
Authors: Claudia D. Baldus, Stephan M. Tanner, Amy S. Ruppert, Susan P. Whitman, Kellie J. Archer, Guido Marcucci, Michael A. Caligiuri, Andrew J. Carroll, James W. Vardiman, Bayard L. Powell, Steven L. Allen, Joseph O. Moore, Richard A. Larson, Jonathan E. Kolitz, Albert de la Chapelle, Clara D. Bloomfield
Journal: Blood (2003)