tbuckley/cabot-search huggingface dataset:
Abstract 489: Hypoxia-mediated ROS enhances HGF-induced cancer cell invasion and suppresses cell cycle progression
Authors: Young H. Lee, Donald P. Bottaro
Journal: Cancer Research (2014)

Abstract The cellular response to hypoxia is a major influence on the aggressiveness of primary tumors, yet much of how this response mechanism influences other signaling pathways is unknown. The MET proto-oncogene, which encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), is often overexpressed in cancers and can drive cell proliferation, invasion, and metastasis. Prior studies demonstrated that the Met tyrosine-kinase receptor drives cell invasion and metastasis under hypoxic conditions, and this invasive phenotype is lost if MET expression is suppressed. Hypoxia also has been shown to sensitize HGF driven invasion through an as yet undefined molecular mechanism. The high mortality rate of metastatic cancer makes it crucial to understand the functional integration of these two prevalent drivers of metastasis, hypoxia and Met signaling, and to identify ways to selectively block cancer cell invasiveness. We show that hypoxia enhanced HGF-mediated invasion in the papillary renal cell (PRC) carcinoma cell lines ACHN and UOK112. Cells under hypoxic conditions accumulated high levels of ROS, which in turn sensitized the Erk pathway to enhance HGF-driven invasion. ROS accumulation was also associated with suppression of MAPK phosphatase DUSP2 mRNA. The other prevalent arm of Met mediated signaling, the PI3K/Akt pathway, normally drives cell survival and proliferation. In hypoxic conditions, however, Akt activation is suppressed by ROS mediated PP2a activation. This is accompanied by metabolic shift towards autophagy and decreased cell cycle progression. Thus hypoxia modifies HGF biologic program by enhancing invasion and suppressing proliferation. Identifying the specific effectors responsible for the integration these signaling pathways will improve our understanding of pro-metastatic invasiveness and potentially identify novels targets for its selective blockade. Citation Format: Young H. Lee, Donald P. Bottaro. Hypoxia-mediated ROS enhances HGF-induced cancer cell invasion and suppresses cell cycle progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 489. doi:10.1158/1538-7445.AM2014-489
Abstract 1254: Novel acetal and halogen oridonin analogues potently induce apoptosis in prostate cancer cell lines <i>via</i> induction of p53/p73 and PUMA expression
Authors: Yu Ke, Zhongbo Liu, Hong-Min Liu, Xiaolin Zi
Journal: Cancer Research (2014)

Abstract Isodon rubescens (a Chinese herb named “Donglingcao”) has been used as a folk, botanical medicine for treatment of inflammatory diseases and cancer for many years. Oridonin, a complex ent-kaurane diterpenoid that was isolated from this herb, has been demonstrated as a promising anti-cancer agent. However, the anti-cancer potency of oridonin and its in vivo stability remains unsatisfactory for its clinical development. Therefore, we have designed and synthesized a series of acetal and halogen oridonin analogues at the 20 position of the chemical skeleton. All these analogues have demonstrated improved potency over oridonin against the growth of bladder, breast, colon, lung and prostate cancer cell lines with low micromolar to submicromolar IC50 values. In particular, compound 10 potently induces apoptosis in both androgen-sensitive and castration-resistant prostate cancer cell lines, including LAPC4, LNCaP, 22Rv1, PC3 and DU145. Compound 10 increased the expression of YAP1 and its phosphorylation, as well as expression of p73 and p53, which further led to upregulation of p73/p53 target gene PUMA. The apoptotic effect of compound 10 is at least in part dependent on the existence of p53 and PUMA. These results demonstrated the potential of compound 10 as a novel apoptosis inducer for treatment of prostate cancer. The evaluation of the in vivo anti-tumor efficacy of compound 10 is in progress. Note: This abstract was not presented at the meeting. Citation Format: Yu Ke, Zhongbo Liu, Hong-Min Liu, Xiaolin Zi. Novel acetal and halogen oridonin analogues potently induce apoptosis in prostate cancer cell lines via induction of p53/p73 and PUMA expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1254. doi:10.1158/1538-7445.AM2014-1254
False-Positive Gram-Stained Smears
Authors: Charles H. Hoke
Journal: JAMA (1979)

The rate per 1,000 smears showing nonviable Gram-negative bacilli (false-positive smears) increased from a baseline of 10.8 to 38.5 following purchase of new culture-collection devices; the rate decreased to 8.0 following replacement of contaminated culture sets. False-positive reports led to changes in therapy for five patients. In addition to being sterile, commercial culture-collection devices should be certified by the manufacturer as being free of stainable microorganisms or as unsuitable for preparation of Gram-stained smears.
siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle
Authors: Karim Bouzakri, Anna Zachrisson, Lubna Al-Khalili, Bei B. Zhang, Heikki A. Koistinen, Anna Krook, Juleen R. Zierath
Journal: Cell Metabolism (2006)
Hyperamylasemia in Diabetic Ketoacidosis: Sources and Significance
Authors: FRANK VINICOR
Journal: Annals of Internal Medicine (1979)

The origins and clinical significance of hyperamylasemia during diabetic ketoacidosis are unclear. We have therefore correlated important clinical and laboratory indices of diabetic ketoacidosis with sequential determinations of serum and urine amylase concentrations, amylase/creatinine clearance ratios, and specific amylase isozyme types. Hyperamylasemia occurred in 79% of our patients with diabetic ketoacidosis, often after admission to the hospital. Among these patients, 48% had pancreatic-type, 36% salivary-type, and 16% mixed-type (pancreatic and salivary) hyperamylasemia. There were no correlations between the presence, degree, or isozyme type of hyperamylasemia and most laboratory or clinical characteristics, including gastrointestinal symptoms. Patients with pancreatic-type hyperamylasemia tended to have higher amylase/creatinine clearance ratios, but it was not possible to unequivocably diagnose acute pancreatitis during diabetic ketoacidosis with current routine clinical or laboratory procedures.
Natural History of Cardiovascular Disease in Patients With Diabetes
Authors: Zvonko Milicevic, Itamar Raz, Scott D. Beattie, Barbara N. Campaigne, Samiha Sarwat, Elwira Gromniak, Irina Kowalska, Edvard Galic, Meng Tan, Markolf Hanefeld
Journal: Diabetes Care (2008)

Atherosclerotic vascular disease is more common in diabetic than in nondiabetic individuals. Diabetic macrovascular disease also has a more severe course with greater prevalence of multiple-vessel coronary artery disease and more diffuse elongated atheromas in affected blood vessels. In this review, we discuss possible reasons for increased incidence of cardiovascular (CV) events in individuals with diabetes. Although an increased prevalence of standard CV risk factors has been clearly documented in association with diabetes, diabetes-related abnormalities, particularly hyperglycemia, also play an important role. Epidemiological studies suggest that the effect of hyperglycemia on CV risk is independent of other known risk factors, but no data from primary interventional trials are available yet. Analysis of datasets from populations that included individuals with impaired glucose tolerance and impaired fasting glucose suggest that the pathogenic role of hyperglycemia on the blood vessel wall already exists in the early stages of glucose intolerance. The effect of postprandial or postchallenge hyperglycemia seems to be greater than the effect of fasting blood glucose abnormalities. The relationship of postprandial glycemia, fasting blood glucose, and CV risk in individuals with diagnosed (or overt) diabetes is less clear, although most reports indicate a greater pathogenic potential of postprandial hyperglycemia rather than fasting hyperglycemia. Based on the results of epidemiological reports, the most appropriate targets in interventional trials are postprandial hyperglycemia or A1C.
Minding the Gap Between Efforts to Reduce Readmissions and Disparities
Authors: Adrian F. Hernandez
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Dissecting Aneurysm of the Aorta: Its Clinical, Electrocardiographic and Laboratory Features
Authors: DAVID C. LEVINSON, DONALD T. EDMEADES, GEORGE C. GRIFFITH
Journal: Circulation (1950)

The literature has been reviewed, and 58 autopsied cases of dissecting aneurysm of the aorta observed at the Los Angeles County Hospital over a ten year period have been carefully studied. Clinical-pathologic correlation has been attempted whenever possible, with emphasis on diagnostic features. The increasing incidence of accurate diagnosis of dissecting aneurysm has been noted, and it is hoped that this review will help solidify the clinical syndrome or syndromes of the condition and thus facilitate diagnosis in dubious instances.
Congenital factor X deficiencies with a defect only or predominantly in the extrinsic or in the intrinsic system: A critical evaluation
Authors: Antonio Girolami, Pamela Scarparo, Raffaella Scandellari, Emanuele Allemand
Journal: American Journal of Hematology (2008)

Congenital Factor X deficiency is commonly classified as type I, in which there is a concomitant decrease of activity and antigen (CRM negative), and in type II, in which activity is low but antigen is normal or near normal (CRM positive). During the past decades it was shown that type II was by itself very heterogeneous. It was shown in fact that some forms showed a defect in all three assay systems (extrinsic, intrinsic, and RVV dependent), whereas others showed a defect only in two of the three systems. Molecular biology analysis, whenever available, has failed so far to supply clear explanations for these discrepancies. The purpose of the present article was an attempt to correlate the clotting activities seen in these two defects with other clotting, chromogenic, immunological assays, and molecular biology results. There are in the literature 10 families that show a predominant defect in the extrinsic system, and four families that show a predominant defect in the intrinsic system. All patients showed a normal, near normal, or reduced level of antigen that is always definitively higher than the clotting counterpart. Molecular biology studies revealed mutations in different exons, namely 2, 4, 5, 6, and 8. These mutations in different exons do not allow any clear genotype-phenotype conclusions, but indicate that mutations in different exons may give rise to the same phenotype. The study underlines the importance of a multipronged evaluation of all cases with Factor X deficiency. In fact only by this approach can an acceptable classification of the defect be reached.
National Health Insurance — Forever Imminent?
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1975)

A physical law of legislative politics holds that if virtually everyone is for something and few are against it, something will be enacted.If the law is valid, why, then, are we still awaiting passage of a national-health-insurance program? Proposals for such insurance formerly provoked raging opposition from one or another segment of medicine and politics. But now, from the White House on down, the naysayers have practically disappeared. In effect, a powerful army sits before an undefended goal but fails to move. Why?The short-term answer is that the veto-slinging Mr. Ford, though committed to eventual passage of an . . .
An unusual treatment for a colonic polyp
Authors: A Viscido
Journal: Gut (2004)

Background: Overexpression of tissue plasminogen activator (t-PA) in pancreatic cancer cells promotes invasion and proliferation in vitro and tumour growth and angiogenesis in vivo.Aims: To understand the mechanisms by which t-PA favours cancer progression, we analysed the surface membrane proteins responsible for binding specifically t-PA and studied the contribution of this interaction to the t-PA promoted invasion of pancreatic cancer cells.Methods: The ability of t-PA to activate plasmin and a fluorogenic plasmin substrate was used to analyse the nature of the binding of active t-PA to cell surfaces.Specific binding was determined in two pancreatic cancer cell lines (SK-PC-1 and PANC-1), and complex formation analysed by co-immunoprecipitation experiments and co-immunolocalisation in tumours.The functional role of the interaction was studied in Matrigel invasion assays.Results: t-PA bound to PANC-1 and SK-PC-1 cells in a specific and saturable manner while maintaining its activity.This binding was competitively inhibited by specific peptides interfering with the interaction of t-PA with annexin II.The t-PA/annexin II interaction on pancreatic cancer cells was also supported by coimmunoprecipitation assays using anti-t-PA antibodies and, reciprocally, with antiannexin II antibodies.In addition, confocal microscopy showed t-PA and annexin II colocalisation in tumour tissues.Finally, disruption of the t-PA/annexin II interaction by a specific hexapeptide significantly decreased the invasive capacity of SK-PC-1 cells in vitro.Conclusion: t-PA specifically binds to annexin II on the extracellular membrane of pancreatic cancer cells where it activates local plasmin production and tumour cell invasion.These findings may be clinically relevant for future therapeutic strategies based on specific drugs that counteract the activity of t-PA or its receptor annexin II, or their interaction at the surface level.
Fibrosis Progression in Nonalcoholic Fatty Liver vs Nonalcoholic Steatohepatitis: A Systematic Review and Meta-analysis of Paired-Biopsy Studies
Authors: Siddharth Singh, Alina M. Allen, Zhen Wang, Larry J. Prokop, Mohammad H. Murad, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2014)
Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog.
Authors: M Pagani, F Lombardi, S Guzzetti, O Rimoldi, R Furlan, P Pizzinelli, G Sandrone, G Malfatto, S Dell'Orto, E Piccaluga
Journal: Circulation Research (1986)

In 57 normal subjects (age 20-60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at approximately 0.25 Hz and a low frequency at approximately 0.1 Hz, with a normalized low frequency:high frequency ratio of 3.6 +/- 0.7. With tilt, the low-frequency component became largely predominant (90 +/- 1%) with a low frequency:high frequency ratio of 21 +/- 4. Acute beta-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency:high frequency ratio induced by tilt. Chronic beta-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency:high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency:high frequency ratio (0.7 +/- 0.1); during tilt, the increase in the low frequency:high frequency ratio (8.3 +/- 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency:high frequency ratio at rest of 2.8 +/- 0.7, which became 17 +/- 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation.(ABSTRACT TRUNCATED AT 400 WORDS)
Low-Dose Acarbose Improves Glycemic Control in NIDDM Patients Without Changes in Insulin Sensitivity
Authors: Adam Jenney, Joe Proietto, Kerin O'Dea, Alison Nankervis, Kathy Traianedes, Helen D'Embden
Journal: Diabetes Care (1993)

OBJECTIVE To examine the impact on metabolic control in NIDDM patients of the alpha-glucosidase inhibitor, acarbose, when administered at a low dose in powdered form. RESEARCH DESIGN AND METHODS Six subjects were recruited for a double-blind cross-over trial using 25 mg powdered acarbose and a placebo 3 times a day with meals for 3 mo. In addition to parameters of diabetes control and body weight, glucose turnover and insulin sensitivity were measured with the hyperinsulinemic/euglycemic clamp technique combined with tracer kinetics. RESULTS None of the subjects showed significant changes in FPG levels or body weight either on the 3-mo course of acarbose or placebo. HbA1c fell significantly from 10.6 ± 1.0 to 9.4 ± 1.3% (P = 0.05) during treatment with acarbose but failed to change on placebo (10.1 ± 1.0 to 11.1 ± 2.0%; P = 0.36). Basal HGP and glucose utilization were unchanged during either of the treatment periods, and hyperinsulinemia produced a similar degree of suppression of HGP before and after each treatment. At a physiological concentration, insulin failed to stimulate glucose clearance in these diabetic patients, and no improvement was seen with acarbose treatment. No changes in plasma lipids or lipoprotein profiles were demonstrated after 3 mo on acarbose. In acute studies, it was shown that administration of acarbose at a dose of 25 mg powder per meal significantly decreased the postprandial glycemic excursion. CONCLUSIONS When administered in the powdered form at the low dose of 25 mg 3 times/day with meals over 3 mo, acarbose was well tolerated by the NIDDM patients and was without side effects. It improved glycemic control by reducing postprandial hyperglycemia, but had no effect on glucose turnover, insulin sensitivity, or lipid profile.
Essentiality of boron for healthy bones and joints.
Authors: R E Newnham
Journal: Environmental Health Perspectives (1994)

Since 1963, evidence has accumulated that suggests boron is a safe and effective treatment for some forms of arthritis. The initial evidence was that boron supplementation alleviated arthritic pain and discomfort of the author. This was followed by findings from numerous other observations epidemiologic and controlled animal and human experiments. These findings included a) analytical evidence of lower boron concentrations in femur heads, bones, and synovial fluid from people with arthritis than from those without this disorder; b) observation evidence that bones of patients using boron supplements are much harder to cut than those of patients not using supplements; c) epidemiologic evidence that in areas of the world where boron intakes usually are 1.0 mg or less/day the estimated incidence of arthritis ranges from 20 to 70%, whereas in areas of the world where boron intakes are usually 3 to 10 mg, the estimated incidence of arthritis ranges from 0 to 10%; d) experimental evidence that rats with induced arthritis benefit from orally or intraperitoneally administered boron; e) experimental evidence from a double-blind placebo-boron supplementation trial with 20 subjects with osteoarthritis. A significant favorable response to a 6 mg boron/day supplement was obtained; 50% of subjects receiving the supplement improved compared to only 10% receiving the placebo. The preceding data indicate that boron is an essential nutrient for healthy bones and joints, and that further research into the use of boron for the treatment or prevention of arthritis is warranted.
Integrated electrode and high density feedthrough system for chip-scale implantable devices
Authors: Rylie A. Green, Thomas Guenther, Christoph Jeschke, Amandine Jaillon, Jin F. Yu, Wolfram F. Dueck, William W. Lim, William C. Henderson, Anne Vanhoestenberghe, Nigel H. Lovell, Gregg J. Suaning
Journal: Biomaterials (2013)
ACUTE OBSTRUCTION OF THE SMALL BOWEL
Authors: F. A. COLLER
Journal: JAMA (1949)

The physiologic and pathologic abnormalities caused by acute obstruction of the small bowel have been studied in many clinics and laboratories. The result has been a better understanding of the problem, but the mortality rate for these lesions is still high. A survey of 198 patients with this lesion, observed in the University Hospital in the years 1934 to 1947, has been made and subjected to critical analysis, with the hope of improving the diagnosis and treatment in similar cases in the future. In all patients included in the study the diagnosis of mechanical intestinal obstruction and its causation was confirmed by operation or necropsy. Patients with primary paralytic ileus and those with nonoperative relief of obstruction have been excluded. It is now recognized 1 that the fluids lost by vomiting and other mechanisms, together with the absent intake of food and drink, result in profound dehydration from water and