tbuckley/cabot-search huggingface dataset:
Identification of mucosal-associated invariant T cells in pancreatic tissue and blood of patients with chronic pancreatitis
Authors: J. Jupp, D. Fine, C. D. Johnson, O. Lantz, S. Gadola
Journal: Gut (2011)

<h3>Introduction</h3> Mucosal-Associated Invariant T cells (MAIT) are recently described human T lymphocytes with possible functions in mucosal antibacterial host defence.1 MAIT express a highly conserved T cell receptor (TCR) alpha chain consisting of an invariant Vα7.2-Jα33 rearrangement.2 Recent evidence suggests a role for T lymphocytes in the pathogenesis of chronic pancreatitis (CP), but little is known about the composition of T cell subsets in this disease.34 Intestinal bacterial overgrowth is common in chronic pancreatitis patients.5 We hypothesised that this antigenic load may promote MAIT infiltration of the pancreas and used flow cytometry to study T lymphocytes in resected pancreatic tissue and blood of patients with chronic pancreatitis. <h3>Methods</h3> Fresh resected pancreatic tissue from five patients with CP (5 males, aged 35–62, median age 43) was diced finely, enzymatically digested and passed through a nylon mesh. Lymphocytes were then isolated using density gradient centrifugation. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of the CP patients and four control patients (2 male, 2 female, aged 31–75, median age 41) using widely established techniques. Isolated tissue lymphocytes and PBMCs were analysed with fluorochrome conjugated antibodies (anti- CD3; CD4; CD8; CD161; TCR Vα7.22 and a live/dead stain) according to standard techniques using a FACSAria. <h3>Results</h3> The ratio of CD4:CD8 T cells found in pancreatic tissue compared to blood in patients with CP trended towards a higher ratio in blood, however the trend was not statistically significant. Double negative (DN) and CD8 MAIT cells (TCR Vα7.2+ CD161) were identified in pancreatic tissue and blood in all patients. The proportion of DN MAIT cells was significantly higher in pancreatic tissue compared to blood in patients with CP: 19.4% (5.7–39.6%) versus 5.2% (1.9–11.1%); p&lt;0.05. The proportion and ratio of CD4 and CD8 T cells was similar in peripheral blood of patients with CP compared to controls. <h3>Conclusion</h3> These preliminary data show that while the distribution of CD4 and CD8 lymphocytes in CP tissue and blood is similar, DN MAIT cells are over-represented in tissue. This suggests a specific role for DN MAIT cells in local immune responses in CP. Further analysis using a larger patient cohort and functional studies to assess the possible role of these cells in the regulation of pancreatic inflammation are required.
Stem cells: roadmap to the clinic
Authors: George Q. Daley
Journal: Journal of Clinical Investigation (2010)

Over the last decade, a remarkable number of papers have been published in which the biology of stem cells is introduced with words and phrases such as "promise," "rapid progress," and "future therapies." To separate myth and hype from reality, the articles in this Stem Cells Review series comprise a rich resource on the state of this fast-paced field and provide a balanced perspective on some of the major advances. They recount what the field has achieved over the past decade and where the field is headed. They also highlight the challenges to be faced in translating what is indeed highly promising science into proven therapies that will regenerate and repair diseased tissues.
Thiamine Propyl Disulfide: Absorption and Utilization
Authors: ALLAN D. THOMSON
Journal: Annals of Internal Medicine (1971)

The absorption and utilization of thiamine propyl disulfide, an allithiamine derivative, was compared with that of thiamine hydrochloride, in normal subjects and in alcoholics with and without thiamine deficiency. Both of these congeners of thiamine enter the circulation via the portal vein from the intestinal tract; oral thiamine propyl disulfide, however, which is sparingly soluble in water, produces significantly higher blood, urine, and cerebral spinal fluid levels than thiamine hydrochloride, which is water-soluble. This is attributed to the fact that intestinal transport of thiamine propyl disulfide, unlike thiamine hydrochloride, is not rate-limited in the dose range tested. Oral thiamine propyl disulfide is effective in correcting laboratory and clinical evidence of thiamine depletion refractory to oral thiamine hydrochloride. Its administration caused a rapid increase in cerebral spinal fluid thiamine and disappearance of lateral rectus palsy in patients with Wernicke's encephalopathy. Thiamine propyl disulfide has not produced any untoward effect with long-term administration. A slight odor makes it less palatable than thiamine hydrochloride and unsuitable for addition to flour and other foods. Sugar-coated preparations of this and other allithiamine derivatives have proved useful in preventing and treating thiamine depletion syndromes in Japan and should be considered for wide use for this purpose in other areas.
Abstract 3277: The Fps/Fes protein-tyrosine kinase serves a stromal tissue-specific supporting role in an orthotopic mouse model of breast cancer
Authors: Shengnan Zhang, Bruce B. Elliott, Peter A. Greer
Journal: Cancer Research (2010)

Abstract Fes (also known as Fps) is a cytoplasmic protein tyrosine kinase that is highly expressed in breast epithelial cells during lactation, as well as in vascular endothelial and myeloid cells. Retrovirally encoded oncogenic alleles of Fps/Fes are associated with tumors in chickens and cats and cause tumors in transgenic mice; however, a role for Fes in human cancer has not been established. We hypothesized that Fes promotes breast tumorigenesis through tumor cell intrinsic functions as well as through functions in stromal tissues including vascular endothelial cells and macrophages. To test the potential tumor cell intrinsic role, AC2M2 cells, a highly metastatic mouse mammary carcinoma cell line, were transduced with expression plasmids encoding wild-type, kinase-inactivated or activated Fes. These cells were then engrafted into the mammary fat pads of nude mice and tumorigenesis was assessed by ultrasound (longitudinal tumor volume measurement), Doppler (tumor-associated vascular flow) and biophotonic imaging of GFP-expressing tumor cells (lung metastasis). There was no obvious difference in tumor growth and angiogenesis at the orthotopic site between each cell line and no apparent difference in lung metastasis. To test the potential stromal role of Fes in breast tumorigenesis, parental AC2M2 cells were injected into the mammary fat pads of wild type and Fes-null nude mice, and tumorigenesis and metastasis were assessed as described above. Wild type mice developed tumors significantly faster than Fes-null mice and there was earlier tumor neovascularization and more recruitment of macrophages. There was also a significantly higher degree of lung metastasis in wild type vs Fes-null mice. These observations are consistent with a tumor promoting role for Fes acting at the level of the vascular endothelium and macrophages. This might include promoting early tumor neovasularization through direct roles in vascular endothelial cells as well as indirect roles associated with macrophages. The increased metastatic potential also suggests roles in both these cell lineages. This provides genetic evidence that the Fes protein-tyrosine kinase represents a potential novel therapeutic target in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3277.
Multiple cell cycles occur in rat hepatocytes cultured in the presence of nicotinamide and epidermal growth factor
Authors: Toshihiro Mitaka, Carol A. Sattler, Gerald L. Sattler, Linda M. Sargent, Henry C. Pitot
Journal: Hepatology (1991)

Multiple rounds of cell division were induced in primary cultures of rat hepatocytes in serum-free medium containing 10 mmol/L nicotinamide and 10 ng epidermal growth factor/ml. Cells per culture almost doubled between day 1 and day 5. The proliferating cells were predominantly mononucleate. The time course of DNA synthesis in cultured hepatocytes showed that peaks of the incorporation of 3H-thymidine were observed at 60 hr and 82 hr after plating. Labeling indices of the cells indicated that almost half the cells were labeled with 3H-thymidine in the periods 48 to 72 hr and 72 to 96 hr after plating. In addition, about 20% of the hepatocytes in culture initiated a second round of the cell cycle between 48 and 96 hr in culture, as demonstrated by the use of continuous treatments with 3H-thymidine and 5-bromo-2'-deoxyuridine. Furthermore, by day 4 of culture, about 40% and 15% of metaphases resulted from a second and third round of cell division, respectively. The cultured hepatocytes on day 5 stained with albumin immunocytochemically, and the activity of tyrosine aminotransferase was induced by dexamethasone and glucagon on day 3. In addition, electron micrographs revealed that dividing cells not only had many characteristics of liver mitochondria and bile canaliculus-like structures, but many also contained a few large peroxisomes with internal crystalline nucleoids.
People and Ideas
Authors: George H. Pollock
Journal: JAMA (1986)

<h3>Institutions and Society, edited by W. F. Bynum, Roy Porter, and Michael Shepherd (Anatomy of Madness, Essays in the History of Psychiatry, vol 2, seminar, London, 1982-1983), 283 pp, $42, New York, Tavistock Publications, 1985.</h3> In an era when physicians are ever increasingly confronted by great upheavals in their professional lives, the opportunity to dip into the past is most welcome. This return is not regression; it is an opportunity for renewal. We can observe how lines of thought developed, how disciplines evolved, how society accepted different ideas about madness and emotional and mental illness, and how institutions came into being to deal with the newer conceptualizations. The two volumes under review provide the reader with an oasis with which to relax, be involved, and be refreshed by scholarly essays in the history of psychiatry. The first volume focuses on<i>People and Ideas</i>and the second on<i>fInstitutions and Society</i>.
Translational Selection on Codon Usage in Xenopus laevis
Authors: Héctor Musto, Stéphane Cruveiller, Giuseppe D'Onofrio, Héctor Romero, Giorgio Bernardi
Journal: Molecular Biology and Evolution (2001)

A correspondence analysis of codon usage in Xenopus laevis revealed that the first axis is strongly correlated with the base composition at third codon positions. The second axis discriminates between putatively highly expressed genes and the other coding sequences, with expression levels being confirmed by the analysis of Expressed sequence tag frequencies. The comparison of codon usage of the sequences displaying the extreme values on the second axis indicates that several codons are statistically more frequent among the highly expressed (mainly housekeeping) genes. Translational selection appears, therefore, to influence synonymous codon usage in Xenopus.
Control of Insulin-Dependent Diabetes with Portable Miniaturized Infusion Systems
Authors: K D Hepp, R Renner, K Piwernetz, H Mehnert
Journal: Diabetes Care (1980)

A method of insulin therapy that appears to achieve better control of diabetes than present conventional methods is the use of insulin infusion devices — either glucose-controlled feedback (closed-loop) systems or the preprogrammed (open-loop) infusion pump. In view of the problems with implantable glucose sensors, we have worked to develop a miniaturized, programmable infusion system. Its use in insulin-dependent diabetic patients to provide either intravenous doses or a continuous subcutaneous insulin infusion resulted in significant reductions in blood glucose levels, glycemic excursions and 24-h glucose excretion.
Abstract 1136: Synergistic inhibition of bioenergetic pathways in pancreatic cancer cells by mitochondria-targeted nitroxide and glycolytic inhibitors
Authors: Gang Cheng, Jacek Zielonka, Joy Joseph, Balaraman Kalyanaraman
Journal: Cancer Research (2012)

Abstract Pancreatic adenocarcinoma is one of the most aggressive cancers with a high fatality rate. Currently available chemotherapy for treating pancreatic cancers is ineffective. Emerging research is focused on drugs targeting bioenergetic pathways in tumor cells. Despite decades of evidence that cancer cells have increased aerobic glycolysis, glycolytic inhibition has failed as a chemotherapeutic approach, due in part to enhanced systemic toxicity of antiglycolytic agents. We hypothesized that a combined inhibition of glycolysis and mitochondrial function may represent an alternate therapeutic approach that can potentially overcome the insufficiency of glycolytic inhibition alone. In this study we investigated the chemotherapeutic efficacy of combining mitochondria-targeted nitroxide, Mito-CP (a nitroxide, carboxy proxyl conjugated to a triphenylphosphonium (TPP+) moiety), and inhibitors of glycolysis, 2-deoxy-D-glucose (2-DG) or 3-bromopyruvate (3-BP) in pancreatic cancer cell lines, PANC-1 and MiaPaCa-2. The relative cytotoxicity and mitochondrial bioenergetic changes in pancreatic cancer cells were assessed. We observed that Mito-CP synergized with glycolytic inhibitors (2-DG or 3-BP) in inducing cell death. Using a Seahorse XF24 extracellular flux analyzer, we determined the combined effects of Mito-CP and 2-DG or 3-BP on cellular mitochondrial function and glycolytic function. The combined treatments induced fast and irreversible inhibition of mitochondrial functions and intracellular ATP depletion. Collectively, these results suggest that targeting mitochondrial bioenergetic metabolism with Mito-CP and glycolytic inhibitors such as 2-DG and 3-BP may be a promising chemotherapeutic strategy in pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1136. doi:1538-7445.AM2012-1136
A Diamond Nanoneedle Array for Potential High‐Throughput Intracellular Delivery
Authors: Xianfeng Chen, Guangyu Zhu, Yang Yang, Beilei Wang, Li Yan, Kenneth Yin Zhang, Kenneth Kam‐Wing Lo, Wenjun Zhang
Journal: Advanced Healthcare Materials (2013)

A dense diamond nanoneedle array is capable of rapidly and conveniently delivering fluorescent probe and drug molecules to a large number of cells. This simple approach paves the way for potential high-throughput delivery of genes, drugs, and fluorescent probes into cells without endocytosis. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Clinical characteristics and factors predicting evolution of asymptomatic IgM monoclonal gammopathies and IgM-related disorders
Authors: E Morra, C Cesana, C Klersy, L Barbarano, M Varettoni, L Cavanna, B Canesi, E Tresoldi, S Miqueleiz, P Bernuzzi, A M Nosari, M Lazzarino
Journal: Leukemia (2004)
MicroRNA Classifiers for Predicting Prognosis of Squamous Cell Lung Cancer
Authors: Mitch Raponi, Lesley Dossey, Tim Jatkoe, Xiaoying Wu, Guoan Chen, Hongtao Fan, David G. Beer
Journal: Cancer Research (2009)

Abstract Non–small cell lung cancer (NSCLC), which is comprised mainly of adenocarcinoma and squamous cell carcinoma (SCC), is the cause of 80% of all lung cancer deaths in the United States. NSCLC is also associated with a high rate of relapse after clinical treatment and, therefore, requires robust prognostic markers to better manage therapy options. The aim of this study was to identify microRNA (miRNA) expression profiles in SCC of the lung that would better predict prognosis. Total RNA from 61 SCC samples and 10 matched normal lung samples was processed for small RNA species and profiled on MirVana miRNA Bioarrays (version 2, Ambion). We identified 15 miRNAs that were differentially expressed between normal lung and SCC, including members of the miR-17-92 cluster and its paralogues. We also identified miRNAs, including miR-155 and let-7, which had previously been shown to have prognostic value in adenocarcinoma. Based on cross-fold validation analyses, miR-146b alone was found to have the strongest prediction accuracy for stratifying prognostic groups at ∼78%. The miRNA signatures were superior in predicting overall survival than a previously described 50-gene prognostic signature. Whereas there was no overlap between the mRNAs targeted by the prognostic miRNAs and the 50-gene expression signature, there was a significant overlap in the corresponding biological pathways, including fibroblast growth factor and interleukin-6 signaling. Our data indicate that miRNAs may have greater clinical utility in predicting the prognosis of patients with squamous cell lung carcinomas than mRNA-based signatures. [Cancer Res 2009;69(14):5776–83]
Epigenetic Inactivation of the Groucho Homologue Gene <i>TLE1</i> in Hematologic Malignancies
Authors: Mario F. Fraga, Maria Berdasco, Esteban Ballestar, Santiago Ropero, Pilar Lopez-Nieva, Lidia Lopez-Serra, José I. Martín-Subero, Maria J. Calasanz, Isabel Lopez de Silanes, Fernando Setien, Sara Casado, Agustin F. Fernandez, Reiner Siebert, Stefano Stifani, Manel Esteller
Journal: Cancer Research (2008)

An undifferentiated status and the epigenetic inactivation of tumor-suppressor genes are hallmarks of transformed cells. Promoter CpG island hypermethylation of differentiating genes, however, has rarely been reported. The Groucho homologue Transducin-like Enhancer of Split 1 (TLE1) is a multitasked transcriptional corepressor that acts through the acute myelogenous leukemia 1, Wnt, and Notch signaling pathways. We have found that TLE1 undergoes promoter CpG island hypermethylation-associated inactivation in hematologic malignancies, such as diffuse large B-cell lymphoma and AML. We also observed a mutual exclusivity of the epigenetic alteration of TLE1 and the cytogenetic alteration of AML1. TLE1 reintroduction in hypermethylated leukemia/lymphoma cells causes growth inhibition in colony assays and nude mice, whereas TLE1-short hairpin RNA depletion in unmethylated cells enhances tumor growth. We also show that these effects are mediated by TLE1 transcriptional repressor activity on its target genes, such as Cyclin D1, Colony-Stimulating Factor 1 receptor, and Hairy/Enhancer of Split 1. These data suggest that TLE1 epigenetic inactivation contributes to the development of hematologic malignancies by disrupting critical differentiation and growth-suppressing pathways.
CLINICAL OUTCOMES USING A PLATELET-FUNCTION GUIDED APPROACH FOR PREVENTION OF ISCHEMIC EVENTS IN PATIENTS WITH STROKE OR TIA
Authors: Jeffrey A. Fowler, Jeremiah Depta, Eric Novak, Irene Katzan, Suzanne Bakdash, Kandice Kottke-Marchant, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2012)
Randomized, double-blind clinical trial to evaluate the efficacy of topical tacalcitol and sunlight exposure in the treatment of adult nonsegmental vitiligo
Authors: M. Rodríguez-Martín, M. García Bustínduy, M. Sáez Rodríguez, A. Noda Cabrera
Journal: British Journal of Dermatology (2009)

Vitiligo is a common skin disease which is difficult to treat. Approximately half of patients acquire the disease before the age of 20 years. This disease has a high stigmatizing impact but no ideal, aetiology-oriented, effective therapy has been found to date. Tacalcitol and other vitamin D analogues have been shown to have stimulating activity both on immunomodulatory mediators and on melanocytes in lesional skin.To investigate the efficacy and safety of tacalcitol ointment plus sunlight exposure in the treatment of nonsegmental vitiligo.A single-centre, randomized, double-blind, vehicle-controlled study including 80 patients with nonsegmental vitiligo was carried out in a specialized outpatient dermatology clinic within a tertiary care, university-affiliated hospital in Spain. Efficacy was assessed by quantification of the lesional repigmentation area at the end of the study compared with the baseline. Tacalcitol (n = 40) or matching placebo ointment (n = 40) was applied once a day at night. Daily exposure to sunlight for 30 min was performed. Treatment was continued for 4 months. The response of the lesions was clinically verified every 2 weeks by a blinded medical investigator. All adverse effects were recorded.Eighty adult patients with nonsegmental vitiligo were recruited. Over 16 weeks, 64 patients completed the study requirements. There was no significant difference in the repigmentation response at the 16-week time point between the vehicle + sunlight exposure and the tacalcitol + sunlight exposure groups. No reduction in the size of the lesions > 25% was observed in the tacalcitol-treated patients. No serious adverse effects were observed.The combination of tacalcitol with heliotherapy has no additional advantages compared with heliotherapy alone.
Prospective study of combined use of bronchial aspirates and biopsy specimens in diagnosis and typing of centrally located lung tumours
Authors: E. Piaton, M.-H. Grillet-Ravigneaux, B. Saugier, H. Pellet
Journal: BMJ (1995)

To determine the diagnostic accuracy of examining bronchial secretions in pulmonary cytopathology and whether cytology and histopathology can complement each other in routine practice among lung specialists.A prospective study comparing 1225 cytological and biopsy results, conducted during 1987-93. Tumours were confirmed by histopathology, imaging techniques, or clinical outcome and imaging techniques combined.11 lung or internal medicine units, France.1128 patients (874 men; 254 women) aged 65.3 (SD 13.7) years who underwent fibreoptic bronchoscopy for various pulmonary symptoms.Exact concordance between cytological and biopsy results was obtained in 1036/1187 (87.3%) satisfactory specimens. In all 574 lung tumours were diagnosed. One case (0.08%) was a false positive cytological diagnosis in a patient with tuberculosis. Patients with lung cancer were more likely to have positive cytological results than positive biopsy results (P < 0.001). Agreement in tumour typing was observed in 375/424 (88.4%) cases, when non-small cell carcinomas, small cell carcinomas and undifferentiated carcinomas were separated. In the 11 patients with squamous cell carcinomas in situ, eight (72.7%) of the carcinomas were diagnosed cytologically as squamous cell. Unsatisfactory material was obtained in only 20 (1.6%) and 19 (1.6%) cases by cytology and biopsy respectively. Examinations had to be repeated in 86 (7.6%) patients.Examination of bronchial secretions complements histopathology in both diagnosing and typing lung tumours and could be performed more systematically in patients undergoing fibreoptic bronchoscopy.