tbuckley/cabot-search huggingface dataset:
Down-regulation of phosphatase and tensin homolog by hepatitis C virus core 3a in hepatocytes triggers the formation of large lipid droplets
Authors: Sophie Clément, Marion Peyrou, Andrea Sanchez-Pareja, Lucie Bourgoin, Pierluigi Ramadori, David Suter, Manlio Vinciguerra, Kevin Guilloux, Stephanie Pascarella, Laura Rubbia-Brandt, Francesco Negro, Michelangelo Foti
Journal: Hepatology (2011)

Abstract: Hepatitis C virus (HCV) perturbs the host's lipid metabolism and often results in hepatic steatosis. In nonalcoholic fatty liver disease, the intrahepatic down-regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a critical mechanism leading to steatosis and its progression toward fibrosis and hepatocellular carcinoma. However, whether an HCV infection triggers the formation of large lipid droplets through PTEN-dependent mechanisms is unknown. We assessed PTEN expression in the livers of patients infected with HCV genotype 1 or 3 with or without steatosis. The role of PTEN in the HCV-induced biogenesis of lipid droplets was further investigated in vitro with hepatoma cells transduced with the HCV core protein of genotype 1b or 3a. Our data indicate that PTEN expression was down-regulated at the posttranscriptional level in steatotic patients infected with genotype 3a. Similarly, the in vitro expression of the HCV genotype 3a core protein (but not 1b), typically leading to the appearance of large lipid droplets, down-regulated PTEN expression by a mechanism involving a microRNA-dependent blockade of PTEN messenger RNA translation. PTEN down-regulation promoted in turn a reduction of insulin receptor substrate 1 (IRS1) expression. Interestingly, either PTEN or IRS1 overexpression prevented the development of large lipid droplets, and this indicates that the down-regulation of both PTEN and IRS1 is required to affect the biogenesis of lipid droplets. However, IRS1 knockdown per se did not alter the morphology of lipid droplets, and this suggests that other PTEN-dependent mechanisms are involved in this process. Conclusion: The down-regulation of PTEN and IRS1 is a critical event leading to the HCV genotype 3a–induced formation of large lipid droplets in hepatocytes. (HEPATOLOGY 2011;)
An Assessment of Orthotopic Liver Transplantation in Acute Liver Failure
Authors: Roger Williams, A. E. S. Gimson
Journal: Hepatology (1984)

Mortality of fulminant hepatic failure with standard supportive therapy is high (80 to 85%), but unfortunately most patients present to hospital already in Grade IV encephalopathy with severe liver dysfunction, and many have secondary organ damage. If seen earlier, during Grade III encephalopathy, recent experience with charcoal hemoperfusion can give good results (65% survival). Transplantation has a place in those patients who do not respond, and in cases with early Grade IV encephalopathy. Transplantation should also be considered in patients with subacute hepatic failure in whom mortality is equally high and progression to cirrhosis may occur in those who recover. In both groups, the ability to correct the hemorrhagic diathesis and an adequate supply of donor organs are essential to achievement of a successful transplant at this critical time.
Dissection of the grass allergen–specific immune response in patients with allergies and control subjects: T-cell proliferation in patients does not correlate with specific serum IgE and skin reactivity☆☆☆★
Authors: P.A. Würtzen, R.J.J. van Neerven, J. Arnved, H. Ipsen, S.H. Sparholt
Journal: Journal of Allergy and Clinical Immunology (1998)
Apoptosis (Programmed Cell Death) in Arteries of the Neonatal Lamb
Authors: Aesim Cho, David W. Courtman, B. Lowell Langille
Journal: Circulation Research (1995)

Abstract We have examined whether cell death contributes to postnatal remodeling of arteries in lambs. First, abdominal aortic smooth muscle cell proliferation rates fell from 2.87±0.08% per day at 3 days of age to 1.75±0.15% per day at 21 days. These proliferation rates would yield a 50% increase in DNA content in the absence of cell death. No increase in DNA content was observed ( P &lt;.05 for predicted versus measured accumulation); therefore, significant cell death was inferred. The same analysis did not indicate high cell-death rates in the carotid, renal, or iliac arteries; however, cell death was detected in situ by end-labeling partially degraded DNA with terminal deoxynucleotidyl transferase or by nuclear labeling with propidium iodide, a fluorescent dye that permeates only nonviable cells. Nuclei were labeled in all arteries, although labeling was most frequent in the abdominal aorta, a vessel that regresses substantially after birth. Cell death was apoptotic because DNA extracted from arteries and end-labeled with [ 32 P]dCTP produced a series of low molecular weight bands (DNA ladder) on an agarose gel, a hallmark of apoptosis. The ladder was strong for neonatal abdominal aorta but weak for other arteries. Only weak laddering was observed for fetal abdominal aortas in late gestation, confirming that high apoptosis rates in this vessel were initiated after birth. Intense DNA ladders and frequent in situ labeling indicated high rates of apoptosis in the postnatal intra-abdominal umbilical artery, another vessel that regresses after birth. We conclude that apoptosis contributes to postpartum arterial remodeling . This contribution is greatest in arteries that regress after birth.
Abstract 516: VDR overexpression restores tamoxifen responsiveness.
Authors: Maggie C. Louie, Johnny Laim
Journal: Cancer Research (2013)

Abstract Breast cancer is classified as either Estrogen Receptor (ER) positive or ER negative, depending on the presence or absence of the ERα. Approximately, 70% of breast cancers express ERα, with tamoxifen being the most commonly used treatment. However, prolonged treatment often results in the development of acquired resistance, which has presented a major challenge in development of more effective therapeutics for breast cancer. While many studies have focused on understanding the mechanisms behind the development of tamoxifen resistance, few have been successfully implemented into clinical practice. To mimic acquired resistance, we have established a tamoxifen-resistant cell line by treating MCF-7 cells with tamoxifen over prolong period of time in order to select for the resistant phenotype. Our lab has preliminary data that suggest that the Vitamin D receptor (VDR) is downregulated in tamoxifen-resistant breast cancer cells (MCF-7TamR) when compared to the parental MCF-7 cells. The role of VDR in tamoxifen resistance is unclear; however our preliminary data suggest that tamoxifen resistant cells transfected with a VDR overexpression plasmid displayed decrease cell proliferation when treated with tamoxifen in comparison to cells transfected with an empty vector, suggesting that restoring VDR expression may restore tamoxifen responsiveness. Data from this study will give us a better understanding about the role of VDR in the development of acquired resistance. Citation Format: Maggie C. Louie, Johnny Laim. VDR overexpression restores tamoxifen responsiveness. [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 516. doi:10.1158/1538-7445.AM2013-516
Acute Parenchymatous Hepatic Disease Following General Anesthesia
Authors: Michael H.M. Dykes
Journal: JAMA (1965)

The incidence of acute parenchymatous hepatic disease following 46,923 administrations of general anesthetics was studied. This finding was discovered in only 18 patients. The incidence was one in 1,836 following the administration of halothane; and one in 3,224 following the administration of other general anesthetic agents. This difference has no statistical significance. Four of the eight patients who had developed this finding following the administration of halothane were found to have been subjected to one subsequent administration of the drug. None of these four patients had developed evidence of hepatic dysfunction following the second administration.
Reactive oxygen species production of neutrophils in patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid
Authors: Eiji Ohno, Eiichi Ohtsuka, Yoshio Saburi, Keiji Ono, Hiroshi Kikuchi, Masaru Nasu
Journal: American Journal of Hematology (1999)

We measured N-formyl-methionyl-leucyl-phenylalanine-induced reactive oxygen species production by neutrophils from three patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid using a luminol-enhanced chemiluminescence assay. The maximum level of reactive oxygen species production during all-trans retinoic acid treatment was 58.8 ± 2.3 × 104 (mean ± SEM) counted photons per second (cps), which was significantly higher (p < 0.0001) than that of neutrophils from healthy volunteers (13.3 ± 2.3 × 104 cps). Am. J. Hematol. 62:120–121, 1999. © 1999 Wiley-Liss, Inc.
Percutaneous Edge-to-Edge Mitral Valve Repair Escorted by Left Atrial Intracardiac Echocardiography (ICE)
Authors: Andreas Henning, Iris I. Mueller, Karin Mueller, Christine Zuern, Tobias Walker, Meinrad Gawaz, Juergen Schreieck, Harald F. Langer
Journal: Circulation (2014)
Intermittent Hypoxia Furthers the Rationale for Hypoxia-Inducible Factor-1 Targeting
Authors: Mark W. Dewhirst
Journal: Cancer Research (2007)

Abstract Hypoxia-inducible factor-1 (HIF-1) stabilization is a pivotal event in the response to hypoxic stress. A study in the December 15, 2006 issue of Cancer Research shows that HIF-1 stabilization occurs more robustly as a result of intermittent hypoxia compared with chronic hypoxia. The findings of this study suggest that intermittent hypoxia might influence the efficacy of radiotherapy by more strongly affecting the growth and survival of vascular endothelial cells. This finding offers additional encouragement to efforts to target HIF-1 for cancer therapy. [Cancer Res 2007;67(3):854–5]
Rise in Female-Initiated Sexual Activity at Ovulation and Its Suppression by Oral Contraceptives
Authors: David B. Adams, Alice Ross Gold, Anne D. Burt
Journal: New England Journal of Medicine (1978)

This study was designed to test the hypothesis that women exhibit peaks of sexual activity at ovulation, as would be predicted from estrous effects in animals. Married women who used contraceptive devices other than oral contraceptives experienced a significant increase in their sexual behavior at the time of ovulation. This peak was statistically significant for all female-initated behavior, including both autosexual and female-initiated heterosexual behavior, but was not present for male-initiated behavior except under certain conditions of contraceptive use. Previous failures to find an ovulatory peak may be due to use of measures of sexual behavior that are primarily determined by initiation of the male partner. Women using oral contraceptives did not show a rise in female-initiated sexual activity at the corresponding time in their menstrual cycles, probably owing to the suppression of ovulatory increases in hormone secretion by the oral contraceptives. (N Engl J Med 299:1145–1150, 1978)
Selective activation and functional significance of p38α mitogen-activated protein kinase in lipopolysaccharide-stimulated neutrophils
Authors: Jerry A. Nick, Natalie J. Avdi, Scott K. Young, Lisa A. Lehman, Patrick P. McDonald, S. Courtney Frasch, Marcella A. Billstrom, Peter M Henson, Gary L. Johnson, G. Scott Worthen
Journal: Journal of Clinical Investigation (1999)

Activation of leukocytes by proinflammatory stimuli selectively initiates intracellular signal transduction via sequential phosphorylation of kinases. Lipopolysaccharide (LPS) stimulation of human neutrophils is known to result in activation of p38 mitogen-activated protein kinase (MAPk); however, the upstream activator(s) of p38 MAPk is unknown, and consequences of p38 MAPk activation remain largely undefined. We investigated the MAPk kinase (MKK) that activates p38 MAPk in response to LPS, the p38 MAPk isoforms that are activated as part of this pathway, and the functional responses affected by p38 MAPk activation. Although MKK3, MKK4, and MKK6 all activated p38 MAPk in experimental models, only MKK3 was found to activate recombinant p38 MAPk in LPS-treated neutrophils. Of p38 MAPk isoforms studied, only p38α and p38δ were detected in neutrophils. LPS stimulation selectively activated p38α. Specific inhibitors of p38α MAPk blocked LPS-induced adhesion, nuclear factor-kappa B (NF-κB) activation, and synthesis of tumor necrosis factor-α (TNF-α). Inhibition of p38α MAPk resulted in a transient decrease in TNF-α mRNA accumulation but persistent loss of TNF-α synthesis. These findings support a pathway by which LPS stimulation of neutrophils results in activation of MKK3, which in turn activates p38α MAPk, ultimately regulating adhesion, NF-κB activation, enhanced gene expression of TNF-α, and regulation of TNF-α synthesis.
Rational Local Therapy for Breast Cancer
Authors: Monica Morrow
Journal: New England Journal of Medicine (2002)

In a 1976 lecture to the Society of Surgical Oncology, the late Jerome Urban lamented the loss of a rational approach to the treatment of breast cancer, which he thought had been replaced “by an emotional appeal to the patient's vanity. A great cry has been raised in the public media to save the breast, despite the long-term consequences.”1 In this issue of the Journal, Fisher and colleagues2 and Veronesi and colleagues3 describe the long-term outcomes of two pivotal randomized trials comparing breast-conserving surgery and mastectomy. These studies document how far our understanding of breast cancer has evolved since Urban's . . .
Development of Residency Training in Preventive Medicine
Authors: John C. Hume
Journal: JAMA (1966)

The existing pattern for training physicians for specialty practice following medical school and internship is a relatively modern development. While many hospitals had resident medical officers during the 19th century, apparently the first residency system in its modern sense was established by Halsted at the Johns Hopkins Hospital in 1890.<sup>1</sup>The first listing of residencies inThe Journaldid not appear until 1927. At that time there were 1,776 positions offered. Table 1 shows the growth of such programs in relation to the numbers of medical schools, medical graduates, internships offered, and residencies offered for selected years. These figures emphasize the modernity of residency programs and demonstrate certain landmarks and trends in the education of physicians. The major points of interest are perhaps the following: The sharp decline in the number of medical schools and graduates between 1905 and 1920—reflecting the revolution in medical education resulting in the
OPERATIVE TREATMENT OF CEREBRAL PALSY OF SPASTIC TYPE
Authors: WILLIAM T. GREEN
Journal: JAMA (1942)

In surgical procedures directed toward chronic disease impressions of results are often misleading. It is necessary to pause at intervals and do end result determinations on groups of cases to make decisions as to the efficacy of various procedures. It has seemed wise to us to review the orthopedic operations for cerebral palsy of the spastic type which have been done during the preceding fifteen years, 1925-1940, at the Children's Hospital in Boston. In addition to these cases, we have added certain ones in which operations were done by one of us at the Peter Brent Brigham Hospital. The cases included are those which might be called by the orthopedist spastic paralysis and by the neurologist cerebral palsy of the pyramidal tract type. For practical purposes, we have emphasized the term spastic paralysis, since spasticity from whatever origin—intracranial or spinal—was the criterion by which patients were placed in this series.
A monoclonal antibody against mutated nucleophosmin 1 for the molecular diagnosis of acute myeloid leukemias
Authors: Alicja M. Gruszka, Serena Lavorgna, Maria Irno Consalvo, Tiziana Ottone, Chiara Martinelli, Mario Cinquanta, Giuseppe Ossolengo, Giancarlo Pruneri, Francesco Buccisano, Mariadomenica Divona, Michele Cedrone, Emanuele Ammatuna, Adriano Venditti, Ario de Marco, Francesco Lo-Coco, Pier Giuseppe Pelicci
Journal: Blood (2010)
Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.
Authors: W H Martin, R J Spina, E Korte, K E Yarasheski, T J Angelopoulos, P M Nemeth, J E Saffitz
Journal: Journal of Clinical Investigation (1991)

To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced.
Retroperitoneal Perforation during ERCP and Endoscopic Sphincterotomy: Causes, Clinical Features and Management
Authors: D. F. Martin, D. E. F. Tweedle
Journal: Endoscopy (1990)

Eleven patients with retroperitoneal perforation complicating endoscopic management of bile duct obstruction were seen over a seven-year period. In nine patients endoscopic sphincterotomy or pre-cut papillotomy had been performed, but in two who had not undergone sphincterotomy perforation occurred because of the penetration of a guidewire during attempts to negotiate a malignant bile duct stricture. Eight out of eleven patients remained asymptomatic, and all recovered with conservative management. Asymptomatic retroperitoneal perforation can complicate therapeutic ERCP even when sphincterotomy is not performed, but conservative management is usually effective if the complications is recognized immediately.
Liver phospholipid transfer protein (PLTP) expression with a PLTP-null background promotes very low-density lipoprotein production in mice
Authors: Amirfarbod Yazdanyar, Xian-Cheng Jiang
Journal: Hepatology (2012)

It is known that plasma phospholipid transfer protein (PLTP) activity influences lipoprotein metabolism. The liver is one of the major sites of lipoprotein production and degradation, as well as of PLTP expression. To address the impact of liver-expressed PLTP on lipoprotein metabolism, we created a mouse model that expresses PLTP in the liver acutely and specifically, with a PLTP-null background. This approach in mouse model preparations can also be used universally for evaluating the function of many other genes in the liver. We found that liver PLTP expression dramatically increases plasma levels of non–high-density lipoprotein (HDL) cholesterol (2.7-fold, P &lt; 0.0001), non-HDL phospholipid (2.5-fold, P &lt; 0.001), and triglyceride (51%, P &lt; 0.01), but has no significant influence on plasma HDL lipids compared with controls. Plasma apolipoprotein (apo)B levels were also significantly increased in PLTP-expressing mice (2.2-fold, P &lt; 0.001), but those of apoA-I were not. To explore the mechanism involved, we examined the lipidation and secretion of nascent very low-density lipoprotein (VLDL), finding that liver PLTP expression significantly increases VLDL lipidation in hepatocyte microsomal lumina, and also VLDL secretion into the plasma. Conclusion : It is possible to prepare a mouse model that expresses the gene of interest only in the liver, but not in other tissues. Our results suggest, for the first time, that the major function of liver PLTP is to drive VLDL production and makes a small contribution to plasma PLTP activity. (HEPATOLOGY 2012)
Breast cancer incidence in US has fallen for first time in 20 years
Authors: Roger Dobson
Journal: BMJ (2007)

The incidence of breast cancer in women in the United States dropped 3.5% a year from 2001 to 2004, the first time it has fallen in 20 years.

A decline in the use of hormone replacement therapy and in screening for breast cancer might explain the trend, say the authors of a report in Cancer (doi: 10.1002/cncr.23044).

The US government's annual report to the nation on the status of cancer 1975-2004 also shows that overall mortality from …
In suspected PE, an age-adjusted<scp>d</scp>-dimer cutpoint improved ability to exclude PE
Authors: Eddy Lang
Journal: Annals of Internal Medicine (2014)

ACP Journal Club15 July 2014In suspected PE, an age-adjusted D-dimer cutpoint improved ability to exclude PEEddy Lang, MDEddy Lang, MDUniversity of Calgary, Calgary, Alberta, Canada (E.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-161-2-201407150-02013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationRighini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA. 2014;311:1117-24. https://pubmed.ncbi.nlm.nih.gov/24643601Clinical Impact RatingsEmergency Med: Hospitalists: Hematology: Critical Care: References1 Torres-Macho J, Mancebo-Plaza AB, Crespo-Giménez A, et al. Clinical features of patients inappropriately undiagnosed of pulmonary embolism. Am J Emerg Med. 2013;31:1646-50. [PMID: 24060320] Google Scholar2 Huckins DS, Price LL, Gilley K. Utilization and yield of chest computed tomographic angiography associated with low positive D-dimer levels. J Emerg Med. 2012;43:211-20. [PMID: 21764536] Google Scholar3 Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-7. [PMID: 19942258] Google Scholar4 Linkins LA, Bates SM, Lang E, et al. Selective D-dimer testing for diagnosis of a first suspected episode of deep venous thrombosis: a randomized trial. Ann Intern Med. 2013;158:93-100. [PMID: 23318311] Google Scholar5 Schouten HJ, Geersing GJ, Koek HL, et al. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ. 2013;346:f2492. [PMID: 23645857] Google Scholar Author, Article, and Disclosure InformationAuthors: Eddy Lang, MDAffiliations: University of Calgary, Calgary, Alberta, Canada (E.L.)This article was published at Annals.org on 1 July 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTromboembolismo pulmonar en pacientes con COVID-19: estudio de prevalencia en un hospital terciarioPulmonary embolisms in patients with COVID-19: A prevalence study in a tertiary hospital 15 July 2014Volume 161, Issue 2Page: JC13KeywordsD-dimerDeep vein thrombosisPatientsProspective studiesPulmonary embolismResearch fundingSpecificityThromboembolismThrombosisVenous thromboembolism ePublished: 15 July 2014 Issue Published: 15 July 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...