tbuckley/cabot-search huggingface dataset:
Subarachnoid Hemorrhage in Type 1 Diabetes
Authors: Miikka Korja, Lena M. Thorn, Stefanie Hägg, Jukka Putaala, Ron Liebkind, Valma Harjutsalo, Carol M. Forsblom, Daniel Gordin, Turgut Tatlisumak, Per-Henrik Groop
Journal: Diabetes Care (2013)

To estimate for the first time the incidence of subarachnoid hemorrhage (SAH) in type 1 diabetes.Using the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study cohort of 4,083 patients with type 1 diabetes (mean age of 37.4 ± 11.8 years at enrollment), we analyzed the incidence of first-ever SAH events.During the follow-up time of 36,680 person-years (median 9.4 years), 15 patients with type 1 diabetes experienced an aneurysmal or nonaneurysmal SAH, and thus the crude incidence of SAH was 40.9 (95% CI 22.9-67.4) per 100,000 person-years. One patient had a verified aneurysmal SAH, and four patients died suddenly of an SAH, which was most likely caused by an aneurysm. SAHs in 10 out of 15 patients were classified as nonaneurysmal SAH, and thus the crude incidence of nonaneurysmal SAH was 27.3 (13.1-50.1) per 100,000 person-years. None of the nonaneurysmal SAHs were fatal. In univariate analysis, current smokers had a hazard ratio of 4.82 (95% CI 1.31-17.81) for nonaneurysmal SAH.The incidence of nonaneurysmal SAH is high among patients with type 1 diabetes. Our findings suggest that nonaneurysmal SAH is a distinct new microvascular complication in type 1 diabetes.
Automated Volumetric Growth Plate Measurement Using Magnetic Resonance Imaging for Monitoring Skeletal Toxicity in Children Treated on Investigational Drug Trials
Authors: AeRang Kim, Eva Dombi, Jeffrey Solomon, Elizabeth Fox, Frank M. Balis, Brigitte C. Widemann
Journal: Clinical Cancer Research (2011)

Targeted anticancer agents have been reported to have side effects on the skeletal system such as thickening of the epiphyseal growth plate in preclinical models of juvenile, but not mature, animals. Careful evaluation of skeletal toxicity in the clinical development of targeted therapies for children is required. We validated a novel method to measure the growth plate volume using MRI.
Prognostic factors in prostate cancer
Authors: R. Montironi
Journal: BMJ (2001)

Prostate cancer is a leading cause of morbidity and mortality in men, accounting for about 30% of all new cases of cancer and 14% of deaths from cancer. Despite considerable advances in our ability to detect and treat prostate cancer, there have been no significant corresponding decreases in morbidity and mortality.1 The two main issues for clinicians and pathologists involved in prostate cancer are early detection of the cancer and identifying the prognostic factors that predict outcome in individual patients.2

Early detection of prostate cancer, preferably in the preinvasive phase (in lesions such as high grade prostatic intraepithelial neoplasia), is important if a treatment can be found that will arrest development of the cancer. Although a relatively new concept, chemoprevention is a promising strategy for preventing or arresting the development of prostate cancer and is most effective in the early stages of cancer formation, when reversibility may be feasible.3

Much research effort has also gone into the prognostic factors that can predict outcome in individual patients with prostate cancer, and these were the subject of two recent international consensus conferences. 4 5 The goal is to tailor the therapeutic approach to the clinical, morphological, and molecular features of each patient. Many of the clinically important predictive factors in prostate cancer are still derived from a pathologist's examination of tissue specimens using light microscopy, but the challenge of assembling the information is such that the use of artificial neural networks is expected to improve accuracy in diagnosis, …
Activity of P-Glycoprotein in B-Cell Chronic Lymphocytic Leukemia Determined by a Flow Cytometric Assay
Authors: C. Ludescher, W. Hilbe, W. Eisterer, E. Preuss, C. Huber, M. Gotwald, J. Hofmann, J. Thaler
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Activity of P-Glycoprotein in B-Cell Chronic Lymphocytic Leukemia Determined by a Flow Cytometric Assay Get access Christof Ludescher, Christof Ludescher Department of Internal Medicine, University of InnsbruckAustria Correspondence to : Christof Ludescher, M.D., Department of Internal Medicine, University of Innsbruck, Anichstraπe 35, A-6020 Innsbruck, Austria. Search for other works by this author on: Oxford Academic PubMed Google Scholar Wolfgang Hilbe, Wolfgang Hilbe Department of Internal Medicine, University of InnsbruckAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar Wolfgang Eisterer, Wolfgang Eisterer Department of Internal Medicine, University of InnsbruckAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar Eugen Preuss, Eugen Preuss E. Preuss, M. Gotwald, J. Hofmann Institute of Medical Chemistry and Biochemistry, University of InnsbruckAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar Christian Huber, Christian Huber Institute of Radio chemistry, University of InnsbruckAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar Markus Gotwald, Markus Gotwald E. Preuss, M. Gotwald, J. Hofmann Institute of Medical Chemistry and Biochemistry, University of InnsbruckAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar Johann Hofmann, Johann Hofmann E. Preuss, M. Gotwald, J. Hofmann Institute of Medical Chemistry and Biochemistry, University of InnsbruckAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar Josef Thaler Josef Thaler Department of Internal Medicine, University of InnsbruckAustria * See “Notes” section following “References”. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 21, 3 November 1993, Pages 1751–1758, https://doi.org/10.1093/jnci/85.21.1751 Published: 03 November 1993 Article history Received: 24 May 1993 Revision received: 15 July 1993 Accepted: 03 August 1993 Published: 03 November 1993
Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis
Authors: Agesilao D’Arienzo, Luigi Celentano, Alessandro Scuotto, Pasqualina Di Siervi, Vinicio Lombardi, Giovanni Squame, Gabriele Mazzacca
Journal: Hepatology (1988)

In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function tests were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.
Altered keratin 17 peptide ligands inhibit in vitro proliferation of keratinocytes and T cells isolated from patients with psoriasis
Authors: Zhu Shen, Ling Chen, Yu-F. Liu, Tian-W. Gao, Gang Wang, Xue-L. Fan, Jian-Y. Fan, Ping-S. Fan, Chun-Y. Li, Bin Liu, Yu-P. Dang, Cheng-X. Li
Journal: Journal of the American Academy of Dermatology (2006)
Gastrointestinal Damage Associated with the Use of Nonsteroidal Antiinflammatory Drugs
Authors: Miles C. Allison, Allan G. Howatson, Caroline J. Torrance, Frederick D. Lee, Robin I. Russell
Journal: New England Journal of Medicine (1992)

Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may lead to inflammation of the small intestine associated with occult blood and protein loss. The aim of this study was to investigate the prevalence and structural correlates of this enteropathy.
Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma
Authors: DunFa Peng, TianLing Hu, Mohammed Soutto, Abbes Belkhiri, Alexander Zaika, Wael El-Rifai
Journal: Gut (2013)

<h3>Objective</h3> To investigate the potential tumour suppressor functions of glutathione peroxidase 7 (GPX7) and examine the interplay between epigenetic and genetic events in regulating its expression in oesophageal adenocarcinomas (OAC). <h3>Design</h3> In vitro and in vivo cell models were developed to investigate the biological and molecular functions of GPX7 in OAC. <h3>Results</h3> Reconstitution of GPX7 in OAC cell lines, OE33 and FLO-1, significantly suppressed growth as shown by the growth curve, colony formation and EdU proliferation assays. Meanwhile, GPX7-expressing cells displayed significant impairment in G1/S progression and an increase in cell senescence. Concordant with the above functions, Western blot analysis displayed higher levels of p73, p27, p21 and p16 with a decrease in phosphorylated retinoblastoma protein (RB), indicating its increased tumour suppressor activities. On the contrary, knockdown of GPX7 in HET1A cells (an immortalised normal oesophageal cell line) rendered the cells growth advantage as indicated with a higher EdU rate, lower levels of p73, p27, p21 and p16 and an increase in phosphorylated RB. We confirmed the tumour suppressor function in vivo using GPX7-expressing OE33 cells in a mouse xenograft model. Pyrosequencing of the GPX7 promoter region (−162 to +138) demonstrated location-specific hypermethylation between +13 and +64 in OAC (69%, 54/78). This was significantly associated with the downregulation of GPX7 (p&lt;0.01). Neither mutations in the coding exons of GPX7 nor DNA copy number losses were frequently present in the OAC examined (&lt;5%). <h3>Conclusions</h3> Our data suggest that GPX7 possesses tumour suppressor functions in OAC and is silenced by location-specific promoter DNA methylation.
In vivo interaction of antibodies with cell surface antigens. A mechanism responsible for in situ formation of immune deposits in the zona pellucida of rabbit oocytes.
Authors: S Matsuo, P R Caldwell, J R Brentjens, G Andres
Journal: Journal of Clinical Investigation (1985)

It was the aim of this study to test the hypothesis that the interaction of antibodies with antigens expressed on the plasma membrane of cells surrounded by a basement membrane or a basement membrane-like structure results in in situ formation of immune deposits. Ovary was chosen for the experiments because we found that a well-characterized protein, angiotensin-converting enzyme (ACE), is expressed in a diffuse pattern on the plasma membrane of mature oocytes. To investigate the events following the in vivo interaction of oolemma-ACE with its antibody, rabbits were injected with goat anti-rabbit ACE gamma-globulin or with Fab fragments of goat anti-rabbit ACE IgG in an ear vein for a maximum of 4 d; they were followed for up to 20 d thereafter. Ovary tissue was studied by immunofluorescence, and immunoelectron, light, and transmission electron microscopy. The results of this study document two new findings: First, that ACE is expressed on the oolemma of rabbit oocytes. Second, that the in vivo interaction of divalent antibodies to this cell surface antigen induces formation of granular immune deposits in the adjacent zona pellucida through a mechanism of "patching" and "shedding" of immune complexes, similar to that occurring in in vitro systems characterized by interaction of plasma membrane receptors with soluble ligands. This mechanism might have importance in the pathogenesis of Heymann glomerulonephritis and of other immunological diseases involving antigens expressed on the plasma membrane of cells.
Genetic Variants in the UGT1A6 Enzyme, Aspirin Use, and the Risk of Colorectal Adenoma
Authors: A. T. Chan, G. J. Tranah, E. L. Giovannucci, D. J. Hunter, C. S. Fuchs
Journal: JNCI Journal of the National Cancer Institute (2005)

Genetic variation in the uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) enzyme is associated with impaired metabolism of aspirin. To determine whether polymorphisms in the UGT1A6 enzyme modulate the protective benefit of regular aspirin use on colorectal adenoma, we conducted a prospective, nested case-control study of 1062 women who provided blood specimens and detailed data on aspirin use before undergoing lower endoscopy. All statistical tests were two sided. Although UGT1A6 genotype was not associated with overall adenoma risk (multivariable odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.85 to 1.41), functional variant genotypes statistically significantly modified the effect of aspirin on adenoma ( Pinteraction = .02). Among the 616 women with variant genotypes, regular use of aspirin (two or more standard tablets per week) was associated with a decreased risk of adenoma (multivariable OR for adenoma = 0.66 [95% CI = 0.45 to 0.95], OR = 0.63 [95% CI = 0.43 to 0.91] for 0.5–7 standard tablets per week and OR = 0.41 [95% CI = 0.24 to 0.71] for more than 7 tablets per week; Ptrend = .001). In contrast, among women with wild-type genotypes, regular aspirin use was not associated with a reduced risk nor did they obtain any additional benefit with higher doses ( Ptrend = .50). These results were consistent among women with advanced adenomas ( Pinteraction = .003). Thus, functional polymorphisms in the UGT1A6 enzyme statistically significantly modify the effect of aspirin on colorectal neoplasia, and certain subsets of the population, defined by genotype, may obtain differential benefit from aspirin chemoprevention.
β-Catenin Promotes Colitis and Colon Cancer Through Imprinting of Proinflammatory Properties in T Cells
Authors: Shilpa Keerthivasan, Katayoun Aghajani, Marei Dose, Luciana Molinero, Mohammad W. Khan, Vysak Venkateswaran, Christopher Weber, Akinola Olumide Emmanuel, Tianjao Sun, David J. Bentrem, Mary Mulcahy, Ali Keshavarzian, Elena M. Ramos, Nichole Blatner, Khashayarsha Khazaie, Fotini Gounari
Journal: Science Translational Medicine (2014)

Wnt/β-catenin signaling in T cells is activated during polyposis and colon cancer and drives inflammation and tumor growth by promoting expression of T H 17-associated genes including RORγt.
Serum and Synovial Fluid Proteins in Arthritis
Authors: M. Wilkinson, B. S. Jones
Journal: Annals of the Rheumatic Diseases (1962)

Proteinas del suero y del liquid sinovial en la artritis lina gamma del liquido sinovial y la relaci6n entre esta SUMARIO y la del suero fueron superiores en la artritis reumatoide y en la espondilartritis anquilosante que en las demas Se determinaron electroforeticamente las fracciones enfermedades estudiadas.proteinicas en el suero y el liquido sinovial, recogidos Aunque las proteinas del liquido sinovial derivan sobre simultaneamente en sujetos con diferentes enfermedades todo de las proteinas del plasma, se presentan aqui datos articulates.indicando que una parte de la globulin gamma del En la mayoria de las enfermedades los cuadros electro-liquido sinovial de enfermos con artritis reumatoide es foreticos generates fueron similares en el suero y en formada en la membrana sinovial, probablemente por los el liquido sinovial.Sin embargo, las cifras de la globu-linfocitos de infiltracion y por los plasmocitos.
Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers
Authors: Vivian W.Y. Lui, Matthew L. Hedberg, Hua Li, Bhavana S. Vangara, Kelsey Pendleton, Yan Zeng, Yiling Lu, Qiuhong Zhang, Yu Du, Breean R. Gilbert, Maria Freilino, Sam Sauerwein, Noah D. Peyser, Dong Xiao, Brenda Diergaarde, Lin Wang, Simion Chiosea, Raja Seethala, Jonas T. Johnson, Seungwon Kim, Umamaheswar Duvvuri, Robert L. Ferris, Marjorie Romkes, Tomoko Nukui, Patrick Kwok-Shing Ng, Levi A. Garraway, Peter S. Hammerman, Gordon B. Mills, Jennifer R. Grandis
Journal: Cancer Discovery (2013)

Genomic findings underscore the heterogeneity of head and neck squamous cell carcinoma (HNSCC). Identification of mutations that predict therapeutic response would be a major advance. We determined the mutationally altered, targetable mitogenic pathways in a large HNSCC cohort. Analysis of whole-exome sequencing data from 151 tumors revealed the phosphoinositide 3-kinase (PI3K) pathway to be the most frequently mutated oncogenic pathway (30.5%). PI3K pathway-mutated HNSCC tumors harbored a significantly higher rate of mutations in known cancer genes. In a subset of human papillomavirus-positive tumors, PIK3CA or PIK3R1 was the only mutated cancer gene. Strikingly, all tumors with concurrent mutation of multiple PI3K pathway genes were advanced (stage IV), implicating concerted PI3K pathway aberrations in HNSCC progression. Patient-derived tumorgrafts with canonical and noncanonical PIK3CA mutations were sensitive to an mTOR/PI3K inhibitor (BEZ-235), in contrast to PIK3CA-wild-type tumorgrafts. These results suggest that PI3K pathway mutations may serve as predictive biomarkers for treatment selection.
The Impact of Aspect Ratio on the Biodistribution and Tumor Homing of Rigid Soft‐Matter Nanorods
Authors: Sourabh Shukla, Fabian J. Eber, Adithy S. Nagarajan, Nicholas A. DiFranco, Nora Schmidt, Amy M. Wen, Sabine Eiben, Richard M. Twyman, Christina Wege, Nicole F. Steinmetz
Journal: Advanced Healthcare Materials (2015)

The size and shape of nanocarriers can affect their fate in vivo, but little is known about the effect of nanocarrier aspect ratio on biodistribution in the setting of cancer imaging and drug delivery. The production of nanoscale anisotropic materials is a technical challenge. A unique biotemplating approach based on of rod‐shaped nucleoprotein nanoparticles with predetermined aspect ratios (AR 3.5, 7, and 16.5) is used. These rigid, soft‐matter nanoassemblies are derived from tobacco mosaic virus (TMV) components. The role of nanoparticle aspect ratio is investigated, while keeping the surface chemistries constant, using either PEGylated stealth nanoparticles or receptor‐targeted RGD‐displaying formulations. Aspect ratio has a profound impact on the behavior of the nanoparticles in vivo and in vitro. PEGylated nanorods with the lowest aspect ratio (AR 3.5) achieve the most efficient passive tumor‐homing behavior because they can diffuse most easily, whereas RGD‐labeled particles with a medium aspect ratio (AR 7) are more efficient at tumor targeting because this requires a balance between infusibility and ligand–receptor interactions. The in vivo behavior of nanoparticles can therefore be tailored to control biodistribution, longevity, and tumor penetration by modulating a single parameter: the aspect ratio of the nanocarrier.
Cysteinyl-leukotrienes Partly Mediate Eotaxin-induced Bronchial Hyperresponsiveness and Eosinophilia in IL-5 Transgenic Mice
Authors: TAKESHI HISADA, MICHAEL SALMON, YASUYUKI NASUHARA, K. FAN CHUNG
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Eotaxin, a selective chemoattractant for eosinophils, induces lung eosinophilia and bronchial hyperresponsiveness (BHR) when administered intratracheally to interleukin-5 (IL-5) transgenic mice. We determined whether these effects of eotaxin were mediated through the production of cysteinyl-leukotrienes. IL-5 transgenic mice were administered eotaxin (5 micrograms) intratracheally after pretreatment with either diluent or a selective 5-lipoxygenase inhibitor SB210661 or a cysteinyl-leukotriene receptor antagonist, pranlukast. Twenty-four hours later, bronchial responsiveness to acetylcholine was measured and the degree of eosinophil influx was determined in bronchoalveolar lavage fluid (BALF) or in lung tissue. Both pranlukast and SB210661 significantly attenuated BHR induced by eotaxin with logPC(50), which is the concentration of acetylcholine needed to increase baseline insufflation pressure by 50%, from -0.43 +/- 0.16 to 0.39 +/- 0.10 and from -0.22 +/- 0.10 to 0.53 +/- 0.10, respectively (p < 0.05). There was also a significant attenuation of the eosinophil counts in BALF and in airways. BALF levels of leukotriene C(4) (LTC(4)) showed a significant increase after eotaxin from 23.9 +/- 6.7 to 165.0 +/- 35.0 pg/ml (p < 0.05) but were partially suppressed by both SB210661 (71.2 +/- 21.0) and pranlukast (62.7 +/- 11.5). Concentrations of LTB(4) were not significantly changed. We conclude that eotaxin-induced effects in the airways of IL-5 transgenic mice are partly mediated by the activation of 5-lipoxygenase enzyme leading to the generation of cysteinyl-leukotrienes.
Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests.
Authors: A G Davison, P L Haslam, B Corrin, I I Coutts, A Dewar, W D Riding, P R Studdy, A J Newman-Taylor
Journal: Thorax (1983)

Five patients with respiratory disorders associated with hard metal exposure are described. In four patients electron microprobe analysis of bronchoalveolar lavage cells or lung tissue was used to show tungsten and other hard-metal components. Three patients had interstitial pneumonia and fibrosis with unusual multinucleate giant cells. Electron microscopy showed that the giant cells comprised both type II alveolar epithelial cells and alveolar macrophages. The multinucleate macrophages formed a distinctive feature of the bronchoalveolar lavage material but the multinucleate alveolar epithelial lining cells were evident only in lung tissue. The other two patients both suffered from work-related asthma, one of whom also had pulmonary opacities. Bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible.