tbuckley/cabot-search huggingface dataset:
Severe bleeding disorders in children with normal coagulation screening tests
Authors: S T S Durrant
Journal: BMJ (1982)

treatment it could mean that the patient was receiving months of unnecessary, ineffective, and expensive treatment.Ultrasound is likely to prove useful in detecting spontaneous gall-stone recurrence and in monitor- ing the efficacy of postdissolution treatments given in attempts to prevent recurrence.If recurrent stones are detected, however, and treatment options include the possibility of further dissolution therapy, supplementary oral cholecystography will again be necessary.In our present state of ignorance, we agree that it seems sensible to use both cholecysto- graphy and ultrasonography of the gall bladder in monitoring the response to medical treatment and in the follow-up of patients after "confirmed" complete gall-stone dissolution.Indeed, this has been our policy since reliable ultrasonography first became available at Guy's Hospital.The routine use of both techniques is also part of the protocol of the British National Gall-stone Group in their multicentre, postdissolution trial.But to return to Dr Somerville and colleagues' title question: are we being misled?We do not think so, but we do not know and until the incidence of false-positive and false-negative results with both imaging techniques be- comes established, we believe that we should keep an open mind and avoid dogma.
Abstract 5264: Negative regulation of AMPK-dependent metabolic-stress pathways by MIF and D-DT in non-small cell lung carcinoma.
Authors: Stephanie Brock, Beatriz Rendon, Kavitha Yaddanapudi, Robert Mitchell
Journal: Cancer Research (2013)

Abstract AMP-activated protein kinase (AMPK) is a nutrient and metabolic stress sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, D-dopachrome tautomerase (D-DT), have pro-tumorigenic functions in non-small cell lung carcinoma (NSCLC) but have AMPK activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and D-DT's AMPK activating properties in non-transformed cells, MIF and D-DT cooperatively act to inhibit steady state phosphorylation and activation of AMPK in LKB1 wildtype and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and D-DT - acting through their shared cell surface receptor, CD74 - antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production and redox balance resulting in reduced Ca2+/calmodulin-dependent kinase kinase [[Unsupported Character - Symbol Font &amp;#946;]] (CaMKK[[Unsupported Character - Symbol Font &amp;#946;]])-dependent AMPK activation. Combined, these studies indicate that MIF and D-DT cooperate to inhibit AMPK activation in an LKB1-independent manner. This suggests that MIF and D-DT promote a unique and well conserved adaptation pathway that is usurped by the malignant cells in order to counter metabolic stress-induced, AMPK-dependent, tumor suppression. Importantly, because the LKB1 tumor suppressor locus is mutated in over 30% of NSCLC lesions rendering these tumors insensitive to AMPK-dependent growth suppression, the identification of unique AMPK agonists would be expected to have a tremendous impact on NSCLC disease management for clinicians. Taken together, simultaneous therapeutic targeting of both MIF and D-DT represents an innovative and clinically efficacious approach to re-activating metabolic stress-induced tumor suppression in NSCLC malignant lesions. Citation Format: Stephanie Brock, Beatriz Rendon, Kavitha Yaddanapudi, Robert Mitchell. Negative regulation of AMPK-dependent metabolic-stress pathways by MIF and D-DT in non-small cell lung carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5264. doi:10.1158/1538-7445.AM2013-5264
Characterization of various classes of protein adducts.
Authors: S R Tannenbaum, P L Skipper, J S Wishnok, W G Stillwell, B W Day, K Taghizadeh
Journal: Environmental Health Perspectives (1993)

Analysis of the types of protein adducts formed by chemical carcinogens indicate that adducts may be categorized into various classes according to the nature of the carcinogen as well as the amino acid with which they react. Tryptophan(214) of serum albumin was previously shown to react specifically with N-sulfonyloxy-N-acetyl-4-aminobiphenyl. The same residue is now shown to also react with the sulfate esters of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N,N'-diacetylbenzidine. Thus, Trp-214 appears to be a binding site for a variety of activated N-aryl hydroxamic acids. Epoxides and diol epoxides derived from polynuclear aromatic hydrocarbons alkylate carboxylic groups in hemoglobin and serum albumin. Because the esters formed are readily hydrolyzed to dihydrodiols and tetrahydrotetrols which can be determined by GC-MS, it is possible to analyze for a wide range of polyaromatic hydrocarbon (PAH) epoxide adducts. With this approach it was shown that human subjects experiencing exposure to ambient levels of environmental PAH do take up and metabolize chrysene and benzo[a]pyrene. Feral, bottom-dwelling fish inhabiting contaminated waters were also examined. Globin adducts containing certain dihydroxy groups such as those arising in anti-diol epoxide adducts were concentrated by boronate affinity chromatography and further analyzed by HPLC with diode-array UV/visible detection. Four compounds were detected that exhibited spectra characteristic of a polynuclear chromophore. Two of these appeared to be isomers. Further instrumental analysis is needed to elucidate the structure of these unknown putative adducts.(ABSTRACT TRUNCATED AT 250 WORDS)
O10.03 * PHYSIOLOGICAL AND BIOLOGICAL RESPONSES OF HUMAN GLIOBLASTOMAS TO BEVACIZUMAB TREATMENT ASSESSED BY METABOLOMIC FLUX ANALYSIS
Authors: F. Fack, H. Espedal, O. Keunen, A. Golebiewska, N. Obad, L. Zheng, E. Gotlieb, P. Harter, S. Niclou, R. Bjerkvig
Journal: Neuro-Oncology (2014)

We have in two different xenograft model systems of human glioblastoma (GBM) that reflect the genotype and phenotype of human GBMs, assessed using 13C6-glucose metabolomic flux analysis, how the tumors adapt to anti-vascular therapy (bevacizumab treatment). A detailed LC-MS analyses of 13C-labeled metabolites show that the tumors adapt to therapy by undergoing metabolomic re-programming events towards anaerobic respiration (glycolysis). This is characterized by an increased influx of 13C6-glucose into the tumors, leading increased levels of 13C-labeled lactate. Moreover, the LC-MS analyses show that bevacizumab treatment leads to reduced levels of metabolites associated with the tricarboxylic acid cycle (TCA cycle) as well as L-glutamine, indicating a reduced oxidative respiration and less ATP production from the TCA cycle. Depletion in glutathione levels was also observed, indicating that bevacizumab treatment causes oxidative stress in the tumors. Immunohistochemical analysis showed an up-regulation of lactate dehydrogenaseA (LDHA) in the bevacizumab treated tumor core as well as in single tumor cells infiltrating the brain indicating an acidification of the microenvironment that may promote invasion. These observations were further verified in a panel of 8 human GBM patients were paired biopsy samples were obtained before and after bevacizumab treatment. Finally, a detailed flow cytometric ploidy and phenotype marker expression of the tumors before and after bevacizumab treatment indicates that the changes observed represent an adaptive response to therapy and not clonal selection.
Low Rates of Short- and Long-term Graft Loss After Kidney-Pancreas Transplant From a Single Center
Authors: Denise S. Tai, Johnny Hong, Ronald W. Busuttil, Gerald S. Lipshutz
Journal: JAMA Surgery (2013)

Since the 1980s, pancreas transplant has become the most effective treatment strategy to restore euglycemia in patients with type 1 diabetes mellitus. However, technical complications and BK virus nephropathy continue to be important causes of early and late graft loss. These and other complications lead to cited 1- and 3-year graft survival rates of 74% and 67% (pancreas) and 81% and 73% (kidney).To examine our center's outcomes with pancreas-kidney transplant and early BK virus screening and treatment.Prospective study from August 2004 to January 2012.University medical center.Sixty-five patients with type 1 diabetes who underwent simultaneous kidney and pancreas, pancreas after kidney, or pancreas transplant alone at a single center.Pancreas transplant.Pancreas and kidney survival; patient survival; and kidney loss due to BK virus nephropathy.Patient survival at 1, 3, and 5 years was 100%, 98.4%, and 98.4%, respectively. Of 2 early pancreatic allograft losses, 1 was due to thrombosis (1.6%). One- and 5-year pancreas graft survival rates were 95.4% and 92.3%; losses after more than 1 year were due to rejection. Kidney survival rates were 100% and 95.2% at 1 and 5 years; losses were due to nephropathy and noncompliance, with 1 death with function. BK virus incidence was 29.2%, with no graft losses due to BK infection.While pancreas transplant can be complicated by early graft loss, our results suggest that excellent outcomes at 5 years can be achieved. Posttransplant BK virus screening and treatment are essential tools to long-term success.
Incidence of Deep Vein Thrombosis (DVE) in Myeloma Patients Treated with Lenalidomide/ Dexamethasone with Prophylaxis
Authors: N. Nishimura, Y. Terui, A. Ouchi, K. Ueda, H. Nitta, M. Yokoyama, N. Tsuyama, K. Takeuchi, K. Hatake
Journal: Annals of Oncology (2013)
Abstract B94: Gene expression profiling during EMT and MET identifies multiple transcription factors involved in the EMT transcriptional reprogramming
Authors: Maria Voronkova, Joseph Addison, Renata Galeeva, James Denvir, Dongquan Chen, Alexey Ivanov
Journal: Cancer Research (2013)

Abstract Background and Objective: The Epithelial-to-Mesenchymal Transition (EMT) is a developmental program which is often reactivated in aggressive metastatic breast cancer. Several transcription factors (TFs), such as Snail and ZEB can act as master regulators of EMT, directly repressing the gene for E-cadherin. We sought to identify common gene expression signatures characteristic to both EMT and a reverse process, Mesenchymal-to-Epithelial Transition (MET). Methods: Using Affymetrix Exon microarrays we characterized global gene expression changes in two cellular models: normal mammary epithelial HMLE cells induced to undergo EMT by expression of Snail1, Snail2 or ZEB1; and MDA-MB-231LN breast cancer cells induced to undergo MET by depletion of ZEB1 and ZEB2. Results: We identified two large gene sets: 1) 1017 genes down-regulated during EMT and up-regulated during MET, which we designated as MET-specific; and 2) 438 genes up-regulated during EMT and down-regulated during MET, which we designated as EMT-specific. 14 TFs were found in the EMT category. Their functional validation showed that individual overexpression of several of these TFs in HMLE cells was sufficient to elicit partial EMT. Discussion and Conclusions: Our comprehensive analysis of gene expression signatures common to EMT and MET identifies the EMT transcriptional program characteristic to invasive metastatic breast cancer. Grant support: NIH NCRR grant P20 RR16440 and Susan G. Komen for the Cure grant KG110350. Citation Format: Maria Voronkova, Joseph Addison, Renata Galeeva, James Denvir, Dongquan Chen, Alexey Ivanov. Gene expression profiling during EMT and MET identifies multiple transcription factors involved in the EMT transcriptional reprogramming. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B94.
8-Isoprostane as a Biomarker of Oxidative Stress in Interstitial Lung Diseases
Authors: PAOLO MONTUSCHI, GIOVANNI CIABAT TONI, PAOLO PAREDI, PANAGIOTIS PANTELIDIS, ROLAND M. du BOIS, SERGEI A. KHARITONOV, PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Oxidative stress contributes to the pathophysiology of interstitial lung diseases, such as cryptogenic fibrosing alveolitis (CFA), fibrosing alveolitis associated with systemic sclerosis (FASSc) and sarcoidosis. F2-isoprostanes are a series of prostaglandin (PG) F2-like compounds produced in vivo independent of cyclooxygenase, as products of the radical-catalyzed lipid peroxidation. Measurement of the concentrations of F2-isoprostanes has proved to be valuable in assessing oxidative stress in vivo. The aim of this study was to measure 8-epi-PGF2 α concentrations, one of the most abundant F2-isoprostane in humans, in bronchoalveolar lavage (BAL) in normal subjects and to compare them to those observed in patients with CFA (n = 9), FASSc (n = 8) and sarcoidosis (n = 10). 8-epi-PGF2 α was detectable in BAL fluid in normal subjects (9.6 ± 0.8 pg/ml) and its concentrations were increased approximately 5-fold in patients with CFA (47.4 ± 7.0, p < 0.001) and FASSc (43.2 ± 3.3, p < 0.001). 8-epi-PGF2 α was also increased in patients with sarcoidosis, although to a lesser extent (12.0 ± 0.70 pg/ml, p < 0.01). No correlation between 8-epi-PGF2 α and either lung function tests or BAL cell types was observed in any group of patients. Our study shows that the level of oxidative stress is enhanced in patients with interstitial lung diseases as reflected by increased concentrations of 8-epi-PGF2 α in BAL fluid.
BMA suggests nurses could become gatekeepers of the NHS
Authors: O. Dyer
Journal: BMJ (2002)

Nurses could replace doctors as gatekeepers to the health system if radical new proposals by the BMA are adopted. The discussion document published last week, represents an abrupt change of policy for the BMA, which has traditionally argued that doctors should be the first point of contact in the NHS.

The BMA proposes that in a primary care setting, nurse practitioners could assess patients with minor ailments. The nurse would direct the more serious cases to a general practitioner. Other patients could be treated by the nurse or sent to …
Logic-Uro-Logic
Authors: Robert E. Fishbein
Journal: JAMA (1969)

To precipitate Beyond the prepuce.—stoned! G. U. Know "You're in" he said A stream of thought To take a ride Down diuretic way And view the plumbing governor Of the mammal. Have a squirt In this enlightened dignity By the peahouse of the August Moon. Here at the way station to the bladder Upstream at the Reniform In the land of the cortical. A jungle of glomerular raspberries What strain filter... And flow the Nile Past the renal pyramids. Down medullary way Calyxing along The integral of calculus And its accretion To precipitate On the fate of phos To rock the boat As I book passage south For spasmodic venture ahead In the rapids of turbulence The muscle is smooth... Prost(r)ate in pain To (w) ring the bladder neck I encyst Dump me down ptosis With my ragged edges Down the tight rope The ureteral ladder Step by step Unto
PREMENSTRUAL PAIN AND CONVOLUTED TUBES.
Authors: FRED B. ROBINSON
Journal: JAMA (1891)

The views in this article occurred to me from the examination of about 700 ova ducts of man, cow, pig, sheep and dog. The substance of the views is that the main premenstrual pain and the pain which women have who are afflicted with tubai disease is essentially due to peristalsis or vermicular motion of the tubes themselves. It is, in short, tubai colic. The method of arriving at this idea was the following: Four years ago I wished to acquire a practical knowledge of the heart and its diseases, so I dissected and examined a large number of the hearts of all animals within range of acquisition. Considerable vivisection was done. It does not require but few vivisections to demonstrate that the essential motive power of the heart is situated in its base. That the main ganglia which control and initiate regular movements to the heart reside in the
Lipids and Lipoprotein Changes After Heart and Liver Transplantation in a Patient with Homozygous Familial Hypercholesterolemia
Authors: P. VALDIVIELSO
Journal: Annals of Internal Medicine (1988)

Changes in lipids and lipoprotein fractions were studied 6 months after a combined heart and liver transplantation in a patient with terminal ischemic heart disease due to homozygous familial hypercholesterolemia. The double transplant was followed by striking decreases in total and low-density-lipoprotein cholesterol levels (-71% and -79%) and content of apolipoprotein B in the low-density-lipoprotein fraction (-74%). There was also an increase in high-density-lipoprotein cholesterol (+7.8%). These changes are greater than those reported with portacaval shunt or plasma exchange. Liver transplantation may be considered in selected patients with homozygous familial hypercholesterolemia.
Epicardial activation of the intact human heart without conduction defect.
Authors: C R Wyndham, M K Meeran, T Smith, A Saxena, R M Engelman, S Levitsky, K M Rosen
Journal: Circulation (1979)

To describe the epicardial ventricular activation sequence in the intact human heart, we obtained epicardial maps from 11 patients with normal QRS undergoing open heart surgery. Epicardial breakthrough (EBT), defined as the emergence of a radially propagating epicardial wavefront, occurred in three to five sites in each patient, and was earliest in the anterior right ventricle, 7--25 msec (mean 17 msec) after the onset of the QRS in all patients. Subsequent EBT occurred in the inferior right ventricle (10 sites in 10 patients), in the anterolateral left ventricle (13 sites in 10 patients), and the inferior left ventricle (eight sites in seven patients). Latest epicardial activation (LEA), defined as the latest site of recordable epicardial activity, occurred in the basal segments in all patients, anteriorly in the right ventricle in five patients, and inferiorly in six patients, four on the right and two on the left. LEA occurred 63--96 msec (mean 77 msec) after the onset of the QRS, and was recorded within 20 msec of the end of the QRS in all patients. Sequence of epicardial activation reflected a fusion process among the wavefronts. This descriptive and quantitative data should provide a suitable basis for comparison of abnormal ventricular activation sequences in patients undergoing surgery for preexcitation or ventricular tachycardia.
Multiple Endocrine Neoplasia Type 1: Scintigraphic and Magnetic Resonance Demonstration
Authors: &NA; D. NGUYEN, ERIC A. WANG
Journal: Clinical Nuclear Medicine (1999)

The authors describe a 41-year-old man with multiple endocrine neoplasia type 1 syndrome characterized by persistent hyperparathyroidism and recurrent Zollinger-Ellison syndrome. An MR examination showed an ectopic mediastinal parathyroid adenoma that was missed by previous parathyroid surgery. Indium-111 pentetreotide SPECT scintigraphy showed in detail the coexistence of a pancreatic islet cell tumor, duodenal carcinoid, and metastatic carcinoid adenopathy that was suboptimally documented by CT examination.
Commentary
Authors: Edward A. Edwards
Journal: JAMA (1969)

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Abstract 939: Chemoprevention of familial adenomatous polyposis by EM011 in the <i>ApcMin/+</i> mouse model
Authors: Shiwang Li, Amy M. Ghaleb, Jing He, Usha Bughani, Agnieszka B. Bialkowska, Vincent W. Yang, Harish C. Joshi
Journal: Cancer Research (2010)

Abstract Abstract Germline mutation of the tumor suppressor gene, adenomatous polyposis coli (APC), is responsible for familial adenomatous polyposis (FAP) with nearly 100% risk for colon cancer at an early age. Although FAP is involved in only 1% of all colon cancer cases, over 80% of sporadic cancers harbor somatic mutations of APC. We show here that 9-bro-noscapine (EM011), a rationally-designed synthetic derivative of a natural non-toxic tubulin-binding alkaloid−noscapine, that reduces the dynamics of microtubules, causes a reversible G2/M arrest in wild type mouse embryonic fibroblasts (MEFs), but an aberrant exit from a brief mitotic block, followed by apoptosis in MEFs isolated from ApcMin/+ mice. Furthermore, both β-catenin levels and activity fell to half the original levels with a concomitant reduction of cell proliferation-inducing cyclin D1, c-Myc, and induction of cytostatic protein p21 prior to caspase-3 activation. Additionally, we show a statistically significant reduction in the number of newly emerging intestinal polyps (to 35% compared with untreated mice) as well as the mean size of polyps (to 42% compared with untreated mice) in EM011-treated ApcMin/+ mice as compared to their sham-treated control littermates. The remaining polyps in the EM011 treated group of ApcMin/+ mice showed evidence of elevated apoptosis as revealed by immunohistochemistry. We failed to detect any evidence of histopathological and hematological toxicities following EM011 treatment. Taken together, our data are persuasive that a clinical trial of EM011 is possible for the prevention/amelioration of polyposis in FAP patients. 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 939.