tbuckley/cabot-search huggingface dataset:
Abstract LB-450: Gene expression of colonic submucosa differs between the inflammatory colitides. A possible reason for differences in IBD-associated CRC incidences
Authors: Michael W. Schäffer, Tanusri Ghosh Roy, Joan C. Smith, Paul E. Wise, Wael M. El-Rifai, Mary K. Washington, David A. Schwartz, Roberta L. Muldoon, Alan J. Herline, Harold L. Moses, Samuel E. Adunyah, Amosy E. M'Koma
Journal: Cancer Research (2011)

Abstract Purpose: Differentiating ulcerative colitis (UC) and Crohn's colitis (CC) may be inaccurate in up to 30% of inflammatory bowel disease (IBD) cases due to overlapping features of these colitides. IBD-associated colorectal cancer (CRC) is frequently diagnosed in an advanced stage. Mass-spectrometric (MS) proteomic patterns found in colonic submucosa have been shown to discriminate UC and CC. To verify this, we aimed to conduct pilot gene expression analyses via microarray assessment of colonic submucosa. The significances of these genes to CRC initiation is as yet not been elucidated. Methods: Laser capture microdissection of colonic submucosa from UC (n=8), CC (n=8), and normal (NL, n=8) samples was performed. The submucosal mRNA was extracted using the PicoPure(TM) RNA Isolation Kit. Comprehensive gene expression analysis of the pooled mRNA from each group was then performed using the Affymetrix GeneChip® Gene 1.0 ST Array System. To detect changes for UC, we compared UC to CC and UC to NL; and for CC, we compared CC to UC and CC to NL. Results: 28,869 genes were represented on the array by 26 probes spread across the full length of each gene. When comparing UC to CC, 138 genes showed at least a 5-fold significant overexpression (p&amp;lt;0.01) with 5 of these genes showing a greater than 30-fold overexpression (Table, all p&amp;lt;0.0001). When comparing CC to UC, 5 different genes were overexpressed at greater than 30-fold change (Table, all p&amp;lt;0.0001). The results of the comparisons of these highly overexpressed genes in UC and CC vs. NL is noted in Table. Conclusions: Microarray assessments show significantly different gene overexpression in UC and CC colonic submucosa, with a few select genes showing dramatic overexpression. Preliminary results indicate that we have the tools in hand to successfully validate the results from the microarray analysis using TR-qPCR and immunohistochemistry (IHC). These genes may assist in delineation of the previously identified differentiating MS submucosal proteomic peaks, potentially facilitating protein biomarker identification to discriminate the inflammatory colitides. These genes may relate to CRC initiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-450. doi:10.1158/1538-7445.AM2011-LB-450
Abstract 893: Anticancer effect and mechanism of prostaglandin E2 receptor EP4 antagonist
Authors: Kazuhiko Nonomura, Katsuyoshi Miyama, Kiyoshi Kanazawa, Takako Okumura, Yoshiyuki Okumura, Masanobu Oshima, Satoru Takahashi, Yukinori Take
Journal: Cancer Research (2012)

Abstract Molecular studies reveal that over-expression of cyclooxygenase-2 (COX-2) is a prominent feature of premalignant and malignant neoplasms. The increased COX-2-mediated prostaglandin-E2 (PGE2) production has a strong association with various cancers, by promoting cell survival, cell growth, migration, invasion, angiogenesis, and immunotolerance. The use of COX-2 selective inhibitors has shown promise in the prevention and treatment of various cancers, however, the chronic use of COX-2 inhibitors is associated with an increased risk of cardiovascular adverse effects. Therefore, there is an urgent need to further understanding of the downstream mechanisms by which PGE2 promotes tumorigenesis and more effective strategies for the treatment of cancer. There are four PGE2 receptors, i.e., EP1, EP2, EP3, and EP4, involved in the pharmacology of PGE2. Accumulating evidences suggest that EP4 is the responsible receptor for PGE2 / COX-2-mediated tumorigenic signals in cancer cells and cancer microenvironment. On the other hands, signals from other prostaglandin receptors, e.g. IP and EP1, are reported to inhibit cancer proliferation or metastasis. These evidences suggest that selective blockade of EP4 would offer anti-cancer efficacy and safety advantages over COX-2 inhibition as cancer therapy. We have developed novel plural EP4 antagonists, with pA2 values of nanomolar range which are selective against other EP receptors. EP4 antagonists inhibited the PGE2-dependent productions of key molecules for cancer promotion i.e. VEGF, IL-23, and IL-6 in macrophages, dendritic cells, and PBMC, respectively. At the same time EP4 antagonist reversed PGE2 -induced TNFα and IL-12 suppression in human whole blood. As a consequence, EP4 antagonists exhibited anti-cancer activity in lung, GI, and prostate cancer models. These results indicate that selective EP4 antagonists show anti-cancer effect mediated by multifaceted mechanisms, and represent an attractive medicine for anti-cancer therapy. 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 893. doi:1538-7445.AM2012-893
Methadone Maintenance Treatment Remains Controversial Even After 23 Years of Experience
Authors: Timothy F. Kirn
Journal: JAMA (1988)

THE MELROSE CLINIC, located on the tenth floor of a high-rise building in New York City's South Bronx, is an anomaly in the methadone maintenance treatment world. It is a clean, bright facility that looks "medical," like an environment conducive to recovery. One of the patients on hand is a young Hispanic woman, a married mother of three. She is petite, almost frail. Like all methadone patients, once a day she downs a small cup of orange drink containing a dissolved diskette of methadone hydrochloride—a synthetic painkiller developed in Germany during World War II—so that she won't have to plunge a needle in her arm. <h3>Exchanging Addictions?</h3> There are people who would say that she has simply exchanged addictions, from illegal heroin to sanctioned methadone, from a needle to a pill. The amount of methadone that patients usually receive at a clinic would stupefy even many addicts. In a person
Circulating microRNAs let-7a and miR-16 predict progression-free survival and overall survival in patients with myelodysplastic syndrome
Authors: Zhuang Zuo, George A. Calin, Henrique M. de Paula, L. Jeffrey Medeiros, Michael H. Fernandez, Masayoshi Shimizu, Guillermo Garcia-Manero, Carlos E. Bueso-Ramos
Journal: Blood (2011)
Priapus in Trouble: So What's New? (For the Articulate, Thelerethism)
Authors: Walter L. Washburn
Journal: JAMA (1988)

To the Editor.  —In answer to a question, Dr Shirley 1 discussed a case of   and this term was later perpetuated in two Letters to the Editor. 2,3 This description does not make sense and is further proof of the fact that while we may be technologically superior to our medical forebears, we certainly are culturally inferior. Priapism is a Latin derivative referring to the penis. For anyone to describe the nipple as suffering from priapism is, at best, inconsistent. I would ask that you use your good offices to correct this unscientific description.
Letter: Student counseling.
Authors: S Crown
Journal: BMJ (1976)

proximal jejunum to absorb glucose.The trapping of available carbohydrate within intact cell walls and alterations of the physical characteristics of the intraluminal contents by unabsorbable carbohydrates may both result in reduced availability of glucose for absorption in the proximal small bowel while increasing its availability in the distal small bowel.The adaptation of the proximal jejunum may then be reversed, resulting in a flatter glucose tolerance curve.It is possible that some diabetic patients might benefit from treatment with wheat bran or other dietary fibres and unavailable carbohydrates.
Prolonged Asymptomatic HIV-1 Infection
Authors: Efisio Sulis, Paolo Lusso, Licinio Contu
Journal: New England Journal of Medicine (2000)

To the Editor: The course of human immunodeficiency virus (HIV) infection is usually more severe in elderly patients than in younger patients.1 We have been following a 78-year-old man who, as a result of a test performed before cataract surgery in 1985, was found to be seropositive for HIV type 1 (HIV-1). The patient is a retired factory worker who is unmarried and heterosexual, has never taken drugs, and has never received blood transfusions. He now lives in Sardinia but previously lived in northern Italy, where he had sexual contacts with prostitutes, the most likely source of infection. He has . . .
Discontinuation of Manufacture of Isocarboxazid-Reply
Authors: Bruce H. Medd
Journal: JAMA (1994)

<h3>In Reply.</h3> —Roche has received a number of inquiries about isocarboxazid, an antidepressant that was discontinued in December 1993. Prior to that, for more than 30 years, isocarboxazid had been prescribed for certain types of depression. At the time it was discontinued, isocarboxazid was not being used extensively. Moreover, Roche believed that new depression therapies, which had been introduced to the marketplace, were capable of treating the types of depression formerly treated by isocarboxazid. With these considerations in mind, Roche management made a decision to discontinue production of isocarboxazid. A decision was also made to make a small supply of isocarboxazid available to those patients, who, during a transition period to a new medication, might need to be eased off isocarboxazid and onto another antidepressant. Since then, we have received a number of inquiries from physicians and patients about the continued availability of the product, and as a result, we
Structure and Evolution of mtanga, a Retrotransposon Actively Expressed on the Y Chromosome of the African Malaria Vector Anopheles gambiae
Authors: Cherise J. B. Rohr, Hilary Ranson, Xuelan Wang, Nora J. Besansky
Journal: Molecular Biology and Evolution (2002)

Here we report the discovery of a novel family of long terminal repeat (LTR)-retrotransposons designated mtanga-Y, specific to the Y chromosome of the African malaria vector, Anopheles gambiae. mtanga-Y elements represent the first Y-linked sequences and the first members of the Ty1-copia superfamily of retrotransposons described from this mosquito. Analysis of a full-length 4,284-bp element revealed the presence of two intact overlapping open reading frames bounded by LTRs of 119 bp. Evidence suggests that the elements are capable of retrotransposition, as transcripts and potential replication intermediates (one-LTR circles) were detected. However, the ∼12 copies of mtanga-Y appear to be clustered rather than dispersed on the Y chromosome. Absent from the Y chromosome of four sibling species (A. arabiensis, A. quadriannulatus, A. melas, and A. merus), similar, but often defective, mtanga elements are present elsewhere in these genomes, as well as in A. gambiae. These data are consistent with a relatively recent invasion of the A. gambiae Y chromosome by an intact element. The presence of functional mtanga-Y elements suggests that the Y chromosome may be a source, not just a sink, for retrotransposons.
THE NERVOUS UNFIT
Authors: S. S. CROCKETT
Journal: JAMA (1910)

It may have been the original intention of our Creator that all human creatures should start the race of life with the same equipment of physical and functional strength, and many generations back in the history of the human family such may have been the case. The profession would be relieved of an ever-present problem if all of God's favored creatures acted and reacted alike to the responsibilities of life, to the daily fight for bread, to the wild chase after wealth, to the exacting demands of social responsibility with all its joys and sorrows, with all its pleasures and disappointments, with all its cares and comforts, with all its successes and all its failures.  That so many fall short in being able to stand the tension of life's responsibility and fail to fill their measure of work at the end, is due to one of the following:
Easy Interpretation of Heterotopic Ossification Demonstrated on Bone SPECT/CT
Authors: Yin Lin, Wan Y. Lin, Chia H. Kao, Shih C. Tsai
Journal: Clinical Nuclear Medicine (2013)

A 29-year-old male patient suffered from paraplegia 6 months after brain injury. Heterotopic ossification was diagnosed based on clinical characteristics such as decreased range of motion at the bilateral hips without infective signs. A planar bone scintigraphy using Tc-MDP showed intensive radiotracer accumulation in the proximal portion of the bilateral femurs and the right acetabulum. The SPECT/CT images showed increased radiotracer accumulation in the adjacent soft tissues of the bilateral hips but not in the bone. The conservative treatment rather than surgical intervention was given according to the findings in bone SPECT/CT images.
Abstract 973: Targeting cancer stem cells by a novel anti-frizzled antibody inhibits pancreatic tumor growth and induces differentiation
Authors: Wan-Ching Yen, Marcus Fischer, John Lewicki, Austin Gurney, Timothy Hoey
Journal: Cancer Research (2011)

Abstract Clinical management of pancreatic cancer over the past years has not been improved and this disease remains the fourth most common cause of cancer-related death. It has been suggested that cancer stem cells drive tumor growth and progression and are resistant to many current therapies. The WNT/beta-catenin pathway, which signals through the Frizzled (FZD) receptor family and co-receptors, plays an important role in regulating cell fate, stem cell self-renewal and maintenance. We have recently demonstrated that inhibition of WNT/beta-catenin pathway by an anti-FZD antibody 18R5 decreased tumorigenicity and induced differentiation in solid tumors. The present study evaluated the anti-tumor effect of OMP-18R5 in a panel of pancreatic tumors. In vivo studies using primary pancreatic xenograft tumor models showed that OMP-18R5 was efficacious against both high and low grade pancreatic tumors. Histologic and gene expression analyses indicated that the 18R5-mediated anti-tumor effect was associated with inhibition of WNT target genes while inducing of mucin expression and tumor cell differentiation. Furthermore, inclusion of OMP-18R5 delayed pancreatic tumor recurrence following termination of gemcitabine. The delay in tumor recurrence by OMP-18R5 treatment was associated with a decrease in cancer stem cell frequency. The combination of OMP-18R5 and gemcitabine further decreased cancer stem cell frequency compared to the single agents. Our findings provide a rationale to target cancer stem cells through interference with WNT/beta-catenin pathway as a therapeutic approach in pancreatic cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 973. doi:10.1158/1538-7445.AM2011-973
Learning from low income countries: Poor countries still provide reasons to train doctors in diseases of poverty
Authors: Shefaly Yogendra
Journal: BMJ (2005)

Learning from low income countries Experience in low income countries should count towards specialist registrar trainingEditor-Richards and Tumwine ask for discussion on the subject of poor countries making the best teachers. 1When will the postgraduate tutors and royal colleges recognise that medical experience in developing countries should be counted towards specialist registrar training?I recently spoke to a specialist registrar whose 12 months in the main teaching hospital in Malawi counted for nothing towards his training.As a specialist registrar training in chest medicine, he will have seen more tuberculosis than most chest physicians working in provincial England will see in a lifetime.This is particularly frustrating as the numbers of cases of tuberculosis are rising progressively in the United Kingdom, and training in the diagnosis and management of this disease needs to be improved as much as possible.
Functional properties of isolated hepatocytes from ethanol-treated rat liver
Authors: Amador Schüller, Jorge Moscat, Emilio Diez, Jose C. Fernandez-Checa, Francisco G. Gavilanes, Angel M. Municio
Journal: Hepatology (1985)

Gluconeogenesis and palmitate incorporation into triacylglycerols and phosphatidylcholine were measured in isolated hepatocytes from control and ethanol–treated rats. Basal gluconeogenesis and its hormonal response decreased in hepatocytes from ethanol–treated animals; palmitate incorporation into triacylglycerols increased. In ethanol–treated rat liver, 45 Ca 2+ uptake and methylating capacity were reduced, and the hormonal response exhibited differences in binding parameters of insulin.
Early repolarization in mice causes overestimation of ventricular activation time by the QRS duration
Authors: Bas J. Boukens, Mark G. Hoogendijk, Arie O. Verkerk, Andre Linnenbank, Peter van Dam, Carol-Ann Remme, Jan W. Fiolet, Tobias Opthof, Vincent M. Christoffels, Ruben Coronel
Journal: Cardiovascular Research (2012)

Transgenic mice are frequently used to investigate the role of genes involved in cardiac conduction. The QRS duration calculated from the electrocardiogram (ECG) is a commonly used measure for ventricular conduction time. However, the relation between ventricular activation and QRS duration calculated from a mouse surface ECG is not well understood. We aim to relate ventricular activation and repolarization patterns with the mouse ECG.Ventricular activation and repolarization patterns generated by high-density optical mapping and a six-lead pseudo-ECG were compared in isolated mouse hearts. In addition, mouse ECGs were simulated in silico. Right-ventricular activation ends later than left-ventricular activation. Final activation coincided with the end of the QRS complex in leads III and aVF, but not in leads I, II, aVR, and aVL. The pattern of early repolarization (at 20% of repolarization, RT20) but not of RT50 or RT80 followed the activation pattern. After sodium channel blockade by ajmaline, total ventricular activation time increased by 10.0 ms, whereas QRS duration increased by only 2.1 ms. In mice carrying a mutation in Scn5a (1798insD), ventricular activation ended after the end of the QRS complex (12.9 ± 0.1 vs. 10.8 ± 0.3).In the mouse, ventricular myocardium activation and early repolarization waves are simultaneously present. This hampers unequivocal interpretation of the duration of the QRS complex as a measure of ventricular activation duration, especially when conduction is slowed. Under these conditions mapping of local activation and repolarization patterns is required for correct interpretation of the ECG.
Quantitative proteomic analysis of radioresistant breast cancer cell lines.
Authors: L Smith, D Potts, O Qutob, MB Watson, AW Beavis, V Garimella, MJ Lind, PJ Drew, L Cawkwell
Journal: Cancer Research (2009)

Abstract Abstract #5074 Background: Resistance to radiotherapy may be a significant factor in the development of local recurrence following surgical resection and radiotherapy. We aimed to develop a novel in vitro model of radioresistance using a breast cancer cell line and to subsequently identify molecular biomarkers which may be associated with the radioresistant phenotype. We utilised a quantitative proteomics technique (iTRAQ) based on MALDI-TOF/TOF mass spectrometry (MS) to identify differentially expressed proteins.&amp;#x2028; Material and Methods: We established 3 novel breast cancer cell sublines which were significantly resistant to radiotherapy when compared with the parental cells. The radioresistant sublines were created by irradiating cells in fractionated doses of 2Gy up to a total dose of 40Gy. Sufficient time was allowed for the cells to recover between subsequent irradiations. A dose response curve was assessed at the end of treatment to demonstrate a statistically significant increase in radioresistance for each novel cell subline when compared with parental cells. One radioresistant/parental cell pair was first analysed using in-solution digestion and liquid chromatographic separation with protein identification by MALDI-TOF/TOF (LC-MALDI analysis) on an Applied Biosystems 4800 Plus instrument. Quantitative iTRAQ (Applied Biosystems) was then performed on the same instrument for all 3 radioresistant/parental cell pairs.&amp;#x2028; Results: A total of 586 and 652 proteins were identified in T47D and T47DRR cells respectively by LC-MALDI. Those proteins identified in both cell lines and any redundant entries were removed to reveal those proteins which were unique to each cell line. In total 244 unique proteins were identified in T47D cells and 311 unique proteins were identified in T47DRR cells.&amp;#x2028; Comparison of the 3 pairs of radioresistant/parental cell samples by iTRAQ revealed a number of differentially expressed proteins. Using a standard ≥2-fold change in expression, these iTRAQ analyses revealed significant changes in the expression of 51 proteins in one or more of the radio-resistant derivatives.&amp;#x2028; Further confirmation by immunoblotting is underway. Currently the decrease in expression of 26S proteasome associated subunits has been confirmed by this method.&amp;#x2028; Conclusion: LC-MALDI and iTRAQ analysis has revealed a large number of candidate proteins which may be associated with a radioresistant phenotype. These now require further confirmatory studies. These MS-based techniques offer a powerful proteomic approach to identify candidate biomarkers which may be involved in radioresistance. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5074.
Genetic adaptation of the human circadian clock to day-length latitudinal variations and relevance for affective disorders
Authors: Diego Forni, Uberto Pozzoli, Rachele Cagliani, Claudia Tresoldi, Giorgia Menozzi, Stefania Riva, Franca R Guerini, Giacomo P Comi, Elisabetta Bolognesi, Nereo Bresolin, Mario Clerici, Manuela Sironi
Journal: Genome biology (2014)

Abstract Background The temporal coordination of biological processes into daily cycles is a common feature of most living organisms. In humans, disruption of circadian rhythms is commonly observed in psychiatric diseases, including schizophrenia, bipolar disorder, depression and autism. Light therapy is the most effective treatment for seasonal affective disorder and circadian-related treatments sustain antidepressant response in bipolar disorder patients. Day/night cycles represent a major circadian synchronizing signal and vary widely with latitude. Results We apply a geographically explicit model to show that out-of-Africa migration, which led humans to occupy a wide latitudinal area, affected the evolutionary history of circadian regulatory genes. The SNPs we identify using this model display consistent signals of natural selection using tests based on population genetic differentiation and haplotype homozygosity. Signals of natural selection driven by annual photoperiod variation are detected for schizophrenia, bipolar disorder, and restless leg syndrome risk variants, in line with the circadian component of these conditions. Conclusions Our results suggest that human populations adapted to life at different latitudes by tuning their circadian clock systems. This process also involves risk variants for neuropsychiatric conditions, suggesting possible genetic modulators for chronotherapies and candidates for interaction analysis with photoperiod-related environmental variables, such as season of birth, country of residence, shift-work or lifestyle habits.