tbuckley/cabot-search huggingface dataset:
Bone Imaging in the Assessment of En Bloc Osteocutaneous Autotransplantation
Authors: MYRON L. LECKLITNER, JOHN J. BEASLEY, MARY C. FINN
Journal: Clinical Nuclear Medicine (1988)

A patient is presented who sustained an avulsed portion of the mandible and all soft tissues of the floor of the oral cavity, requiring an autogenous en bloc transplant to replace the avulsed tissues. The clinical role of bone imaging in assessing the patency of the microvasculature and viability of the vascularized osteocutaneous graft is discussed, and the criticality of the time of image acquisition in prognosticating the success of the transplantation is emphasized.
Abstract 108: Consequences of hepatic JAK2 deficiency for liver metabolism and hepatocarcinogenesis
Authors: Madeleine Themanns, Katrin Friedbichler, Sonja M. Kessler, Michaela Schlederer, Lukas Kenner, Kay-Uwe Wagner, Johannes Haybaeck, Richard Moriggl
Journal: Cancer Research (2014)

Abstract The metabolic syndrome is a frequent disease in the western world due to increased prevalence of obesity and diabetes mellitus. Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome associated with primary stages of hepatocellular carcinoma (HCC). Hepatic JAK2-STAT5 signaling is mainly activated by growth hormone (GH) which controls cellular metabolism. To address the role of hepatic JAK2 in lipid homeostasis and hepatocarcinogenesis, we crossed a mouse model of inflammatory liver cancer caused by hyperactivated GH signaling (GHtg) to mice harboring the hepatocyte-specific deletion of JAK2 (J2KO; using AlfpCre). While excess of GH caused chronic hepatitis, as well as pathologic alterations such as big hepatocytes with large polymorphic nuclei, severe and progressive hepatosteatosis was evident in GHtg:J2KO and J2KO mice as soon as 12 weeks of age. Hepatosteatosis in JAK2 deficient mice, independent of GH overexpression, was due to increased hepatic lipid synthesis and peripheral lipolysis associated with elevated unsaturated fatty acid (FA) and triglyceride (TG) amounts in the liver. However, microvesicular steatosis, which is associated with a more severe pathology, was more abundant in GHtg:J2KO livers accompanied by significantly elevated liver/body weight ratios. Surprisingly, loss of hepatic JAK2 proteins led to delayed hepatocarcinogenesis in aged mice. Currently, we are investigating the involvement of NAFLD in the pathogenesis of HCC development by genetic and histo-pathologic profiling. We will provide molecular and cellular insights responsible for delayed hepatocarcinogenesis in GHtg:J2KO and J2KO mice. Citation Format: Madeleine Themanns, Katrin Friedbichler, Sonja M. Kessler, Michaela Schlederer, Lukas Kenner, Kay-Uwe Wagner, Johannes Haybaeck, Richard Moriggl. Consequences of hepatic JAK2 deficiency for liver metabolism and hepatocarcinogenesis. [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 108. doi:10.1158/1538-7445.AM2014-108
The Synthesis of Phospholipids in Human Atheromatous Lesions
Authors: D. B. ZILVERSMIT, ESTHER L. MCCANDLESS, PAUL H. JORDAN, WALTER S. HENLY, R. F. ACKERMAN, Anne Boals
Journal: Circulation (1961)

Femoral arteries, abdominal aortas, one renal artery, and one coronary artery removed from patients injected with P 32 phosphate showed in most instances an active incorporation of the label into the phospholipids of intima and adventitia. A comparison of the specific activities of arterial plaque and plasma phospholipids suggests that the excess arterial phospholipids are originally derived from synthesis by the arterial wall, or at least undergo continuous renewal in situ.
Abstract A19: Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines
Authors: Max M. van Noesel, Floor A M Duijkers, Renee X. de Menezes, Dominique J. P. M. Stumpel, Pieter Admiraal, Rob Pieters, Jules P P Meijerink
Journal: Cancer Research (2014)

Abstract Background: Epigenetic alterations are inherent to cancer cells, and epigenetic drugs are currently primarily used to treat hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and also exhibit epigenetic alterations involving e.g. apoptotic pathways, which suggests that also these tumors may be sensitive to epigenetic drugs. This notion prompted us to assess molecular and functional effects of low dosage epigenetic drugs in neuro-ectodermal tumor-derived cell lines of pediatric origin. Results: In 17 neuroblastoma (NBL) and 5 peripheral primitive neuro-ectodermal tumor (PNET) cell lines a combination treatment of 5-aza-2′-deoxycytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages was found to reduce proliferation and to induce wide-spread DNA demethylation, accompanied by major changes in gene expression profiles. Approximately half of the genes that were significantly up-regulated upon treatment exhibited a significant demethylation in their promoter regions. In the NBL cell lines, almost every cellular pathway (193/200) investigated showed expression alterations after treatment, especially a marked up-regulation of genes in the p53 pathway. The combination treatment also resulted in up-regulation of known epigenetically regulated genes such as X-chromosomal genes, tissue-specific genes and a limited number of imprinted genes, as well as known tumor suppressor genes and oncogenes. Conclusions: Nanomolar dosages of epigenetic drugs have a dramatic impact on the genomes of neuro-ectodermal tumor derived cell lines, including alterations in DNA methylation and concomitant alterations in gene expression. Citation Format: Max M. van Noesel, Floor A M Duijkers, Renee X. de Menezes, Dominique J. P. M. Stumpel, Pieter Admiraal, Rob Pieters, Jules P P Meijerink. Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A19.
"RATE OF PROGRESS OF FOOD RESIDUES THROUGH THE BOWEL"
Authors: W. H. Hay
Journal: JAMA (1924)

To the Editor:  —InThe Journal, August 23, appeared the report of the bead experiment by Drs. Alvarez and Freedlander. There are two reasons why this is misleading, the first being the acceptance of an apparently normal, which is merely a high average condition, but probably far from normal; the second, that with the use of small beads there is too great opportunity for lodgment in some pocket of the colon of many of these, leading to erroneous conclusions as to the length of time food residues occupy the tract. Several years ago I used colors instead of beads; colors such as carbon black, the blueberry or blackberry, or gelatin colored with cochineal, and my results were far from those of the authors mentioned, even though the experiments were performed with average, consequently subnormal, subjects.  These results, averaged through large numbers, gave forty-eight hours, which did not regard as anything
Physiological basis and interpretation of indices of pulmonary mechanics.
Authors: J M Drazen
Journal: Environmental Health Perspectives (1984)

Tests of pulmonary mechanical function provide information about the state of the lungs, both airways and parenchyma. This information can be extracted from measurements made in experimental animals, especially the combined determination of pulmonary resistance and dynamic compliance. This report discusses the rationale upon which effects of an intervention on the lung periphery can be distinguished from those on more central airways. Further, practical considerations involved in making these measurements are discussed.
Determining the treatment strategy for colorectal neoplastic lesions: endoscopic assessment or the non-lifting sign for diagnosing invasion depth?
Authors: N. Kobayashi, Y. Saito, Y. Sano, N. Uragami, T. Michita, J. Nasu, T. Matsuda, K. Fu, T. Fujii, T. Fujimori, T. Ishikawa, D. Saito
Journal: Endoscopy (2007)

See also: Commentaire de travail de N. Kobayashi et al., pp. 701Endoscopy 2007; 39(08): 844-845DOI: 10.1055/s-0032-1308857
The Protective Dose of the Potent GPIIb/IIIa Antagonist SC-54701A Is Reduced When Used in Combination With Aspirin and Heparin in a Canine Model of Coronary Artery Thrombosis
Authors: Leo G. Frederick, Osman D. Suleymanov, Lucy W. King, Anita K. Salyers, Nancy S. Nicholson, Larry P. Feigen
Journal: Circulation (1996)

Background Fibrinogen receptor antagonists block the fibrinogen-platelet interaction at the GPIIb/IIIa receptors and inhibit thrombus formation. SC-54701 is the active metabolite of SC-54684A, an orally active fibrinogen receptor antagonist. We compared the efficacy of SC-54701A (SCa, hydrochloride salt) with that of aspirin (ASA) or heparin and with combination therapy in a canine model of continuous current injury. Methods and Results Sixty-six dogs were used (6 per treatment). SCa (15-minute loading dose followed by [//] infusion [μg/kg per minute]: (0.87//0.39=1×SCa; 0.52//0.23=0.6×SCa; and 0.425//0.20=0.5×SCa), ASA (2.8 mg/kg), heparin (200 U/kg plus 1000 U/h), or saline (0.1 mL/kg) was administered intravenously. Experimental time was 180 minutes of current. Time to occlusion was increased ( P &lt;.05) by SCa (T=incidence of thrombosis) (1×SCa, &gt;180 minutes [T=0]; 0.6×SCa, 158±15 minutes [T=2]; 0.5×SCa, 130±22 minutes [T=4]), heparin (114±16 minutes [T=5]), and ASA plus heparin (130±11 minutes [T=5]) relative to saline (58±7 minutes [T=6]). Time to occlusion for the SCa treatments was increased compared with ASA (64±7 minutes [T=6]). When 0.5×SCa was administered with ASA plus heparin, time to occlusion was &gt;180 minutes [T=0]. SCa provided complete protection at ≥90% inhibition of ex vivo collagen-induced platelet aggregation. Cyclic flow variations were minimal with SCa or any treatment involving 0.5×SCa and ASA. Conclusions SCa has dose-dependent antithrombotic efficacy and inhibits ex vivo platelet aggregation. ASA, heparin, or saline was ineffective in this model. SCa (0.5×) plus ASA and heparin maximized the antithrombotic effect of this lower dose of SCa.
Apport de la dilatation instrumentale au cours de l'atrésie de l'œsophage opérée: à propos de 19 cas
Authors: N Oumnia, M Lahcene, A Tebaibia, N Matougui, MA Boudjella, B Touchene
Journal: Endoscopy (2008)

But: L'atrésie de l'œsophage est une affection congénitale relativement fréquente, elle doit être recherchée systématiquement chez le nouveau né. Son traitement fait appel à la chirurgie associée parfois à la dilatation instrumentale dans le cas de sténose anastomotique. Le but de ce travail est d'évaluer l'apport de la dilatation instrumentale dans les sténoses anastomotiques des atrésies de l'œsophage opérées.
VARICELLA IN OLD AGE
Authors: J. D. Rolleston
Journal: BMJ (1932)

were normal.The kidneys were both enlarged, almost symmetrically so.They showed a lobulated appearance, with large areas of projecting pale cortex.On section the pale areas involved the external rind of the cortex and the inter- medullary areas.The medullae and pelves of the kidneys were normal.The capsules were not adherent. Microscopical Exam,ninationSections from the anterior tumour mass showed a glandular appearance, but no apparent division into cortex and medullary regions, as in the normal thymus, and writh a distinct absence of Hassall's corpuscles.The main part was composed of round cells about the size of small lymphocytes, with deeply
A Clinical Profile of Paroxysmal Hyperpnea in Cyanotic Congenital Heart Disease
Authors: BEVERLY C. MORGAN, WARREN G. GUNTHEROTH, RONALD S. BLOOM, DONALD C. FYLER
Journal: Circulation (1965)

A large series of patients with cyanotic congenital heart disease and inadequate pulmonary blood flow who required a systemic to pulmonary artery anastomosis was reviewed, along with a small current series of patients unselected as to surgical intervention. Thirty-eight per cent of 190 patients in the first group had definite spells consisting of paroxysmal hyperpnea and increased cyanosis, frequently progressing to loss of consciousness. In the current group, 13 of 24 had spells. In the combined groups, there were three convulsions, eight cerebral vascular accidents, and six deaths due to the spell. Age of onset varied from 1 month to 2 years, with the peak incidence between 2 to 3 months of age. The time of day at which spells occurred was recorded in only 15 patients in the large series: 11 occurred in the morning and four in the evening. In the smaller series, the patients who had only occasional episodes had them exclusively in the morning, whereas the severely affected patients had attacks at almost any time. Precipitating factors, in order of over-all frequency, were crying, defecation, and feeding. The most surprising finding was the lack of correlation of hyperpneic spells with resting arterial desaturation, although all arterial saturations obtained during attacks were quite low. Two patients with observed, typical paroxysms had arterial saturations under sedation of 93 and 98 per cent, in contrast to a patient with a 44-per cent saturation who had had no spells.
Integrating evidence based medicine into routine clinical practice: seven years' experience at the Hospital for Tropical Diseases, London
Authors: Diana Lockwood, Margaret Armstrong, Alison Grant
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Problem</b> Introduction and evaluation of evidence based medicine (EBM) into routine hospital practice. <b>Strategy for change</b> Routine EBM meetings introduced in 1997. <b>Design</b> Review of outcomes of meetings from 1997 to 2004, focusing on their effect on clinical practice. <b>Setting</b> Referral centre for tropical and domestic infectious diseases. <b>Key measure for improvement</b> Outcome of meetings, classified as resulting in a change in practice; confirmation or clarification of existing practice; identification of a need for more evidence; and outcome unclear. <b>Effects of change</b> Examples include a change from inpatient to day case treatment of New World cutaneous leishmaniasis; development of guidelines on the treatment of coinfection with visceral leishmaniasis and HIV; and identification of the need for more data on the efficacy and toxicity of atovaquone-proguanil (Malarone) compared with quinine plus sulfadoxine-pyrimethamine (Fansidar) in the treatment of uncomplicated falciparum malaria, which resulted in a clinical trial being set up. <b>Lessons learnt</b> Incorporation of EBM meetings into our routine practice has resulted in treatment guidelines being more closely based on published evidence and improvements to care of patients. Written summaries of the meetings are important to facilitate change.
Long-Term Follow-Up of Antibiotic-Treated Tropical Sprue
Authors: FREDERICK R. RICKLES
Journal: Annals of Internal Medicine (1972)

Clinical status and intestinal structure and function were evaluated in 17 patients with tropical sprue who, 5 years or more in the past, had been treated with antibiotic agents for at least 6 months. Three patients were experiencing gastrointestinal symptoms, and six had lost weight. Two patients were deficient in folate and two in vitamin B-12. Three patients had steatorrhea: the absorption of xylose was subnormal in 8; that of folic acid, subnormal in 2; and that of vitamin B-12, subnormal in 13. Jejunal morphology was abnormal in eight patients. Intestinal abnormalities, in most instances, represented a reversal to abnormal after cessation of the antibiotic therapy; however, in a few cases of chronic sprue they were persistent changes. Apparently, not only is antibiotic therapy not totally curative in all cases of tropical sprue, but, in persons living in the tropics, there is also a high rate of either relapse or recurrence of intestinal abnormalities after cessation of treatment.
Myocyte Response to β-Adrenergic Stimulation Is Preserved in the Noninfarcted Myocardium of Globally Dysfunctional Rat Hearts After Myocardial Infarction
Authors: Arun J. C. Prahash, Sudhir Gupta, Inder S. Anand
Journal: Circulation (2000)

Cellular mechanisms underlying the diminished inotropic response of remodeled hearts after myocardial infarction (MI) remain unclear.Left ventricular (LV) remodeling and function were assessed by 2D echocardiography and isolated perfused heart studies in 6-week post-MI and sham-operated rats. LV myocytes from sham and noninfarcted MI hearts were used for morphometric and functional studies. Beta-adrenergic receptor (beta-AR) agonist isoproterenol (ISO)-induced contractile response was measured in isolated hearts. The effects of ISO and forskolin on contractile function and calcium transients of isolated myocytes were recorded. ISO-induced cAMP generation was compared in sham and MI myocytes. beta-AR density was measured by radioligand binding. MI hearts were remodeled (LV diameter 8.5+/-0.3 versus 5.7+/-0.3 mm, P:<0.001) and showed global (% fractional shortening 19.1+/-2.5 versus 55.3+/-2.2, P:<0.01) and regional contractile dysfunction of noninfarcted myocardium (% systolic posterior wall thickening 37+/-4 versus 62+/-10, P:<0.01). Isolated heart function (LV developed pressure 58+/-2 versus 72+/-3 mm Hg, P:=0.004) and ISO concentration response were reduced in MI hearts. Myocytes from the noninfarcted LV were structurally remodeled (32% longer and 18% wider), but their contractile response and intracellular calcium kinetics to ISO and forskolin were not diminished. beta-AR receptor density (B(max) 24+/-1.5 versus 22.4+/-1.6 fmol/mg protein) and beta-AR agonist-stimulated cAMP were similar in both groups.Isolated myocytes from the remodeled and dysfunctional myocardium are structurally modified but contract normally under basal conditions and in response to beta-AR stimulation. beta-AR density is preserved in remodeled myocytes. Nonmyocyte factors may be more important in the genesis of contractile dysfunction in the remodeled rat heart up to 6 weeks after MI.
Control of temporal activation of hepatitis C virus-induced interferon response by domain 2 of nonstructural protein 5A
Authors: Marie-Sophie Hiet, Oliver Bauhofer, Margarita Zayas, Hanna Roth, Yasuhito Tanaka, Peter Schirmacher, Joschka Willemsen, Oliver Grünvogel, Silke Bender, Marco Binder, Volker Lohmann, Vincent Lotteau, Alessia Ruggieri, Ralf Bartenschlager
Journal: Journal of Hepatology (2015)

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a multifunctional protein playing a crucial role in diverse steps of the viral replication cycle and perturbing multiple host cell pathways. We showed previously that removal of a region in domain 2 (D2) of NS5A (mutant NS5A(D2Δ)) is dispensable for viral replication in hepatoma cell lines. By using a mouse model and immune-competent cell systems, we studied the role of D2 in controlling the innate immune response.In vivo replication competence of NS5A(D2Δ) was studied in transgenic mice with human liver xenografts. Results were validated using primary human hepatocytes (PHHs) and mechanistic analyses were conducted in engineered Huh7 hepatoma cells with reconstituted innate signaling pathways.Although the deletion in NS5A removed most of the interferon (IFN) sensitivity determining-region, mutant NS5A(D2Δ) was as sensitive as the wild type to IFN-α and IFN-λ in vitro, but severely attenuated in vivo. This attenuation could be recapitulated in PHHs and was linked to higher activation of the IFN response, concomitant with reduced viral replication and virus production. Importantly, immune-reconstituted Huh7-derived cell lines revealed a sequential activation of the IFN-response via RIG-I (retinoic acid-inducible gene I) and MDA5 (Myeloma differentiation associated factor 5), respectively, that was significantly higher in the case of the mutant lacking most of NS5A D2.Our study reveals an important role of NS5A D2 for suppression of the IFN response that is activated by HCV via RIG-I and MDA5 in a sequential manner.
Thrombin activates two stress-activated protein kinases, c-Jun N-terminal kinase and p38, in HepG2 cells
Authors: Hiroshi Mitsui, Toshiyuki Maruyama, Satoshi Kimura, Yoh Takuwa
Journal: Hepatology (1998)

Recently identified c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase are activated by stimuli of various cellular stresses, cytokines, and growth factors. Strong activation of JNK was reported in the regenerating liver, implicating JNK in growth stimulation of hepatocytes. However, it is not known which factors regulate JNK activity in liver cells. In this study, we examined activation of JNK and p38 in HepG2 cells stimulated with heterotrimeric G protein-coupled receptor agonists known as mitogens. Thrombin, lysophosphatidic acid (LPA), and bradykinin (BK) stimulated extracellular signal-regulated protein kinase to similar extents, indicating that HepG2 cells have cell surface receptors for these agonists, which are coupled to intracellular signaling pathways. In contrast, only thrombin strongly activated JNK and p38. Thrombin-induced activation of JNK and p38 peaked at 30 minutes and 15 minutes with maximal stimulation of 13- and 4-fold increases, respectively. LPA and BK failed to activate JNK at all and activated p38 only slightly. Interestingly, thrombin-induced JNK activation was inhibited by protein kinase C down-regulation and the addition of a specific protein kinase C inhibitor. Short-term stimulation of cells with an active phorbol ester also induced JNK activation in HepG2 cells. These results indicate that thrombin is a relatively strong activator for JNK and p38 and might play a role in the regulation of activities of JNK and p38 in liver cells.
In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells.
Authors: C Blat, J Villaudy, M Binoux
Journal: Journal of Clinical Investigation (1994)

IGF Binding Protein-3 (IGFBP-3), the major IGF carrier in the blood, undergoes limited proteolysis which reduces its affinity for IGFs, thus facilitating dissociation. The functional effects of this at the cellular level were studied by comparing two serum pools, one from healthy adults, one from women during late pregnancy when IGFBP-3 proteolysis is increased. Sera were mixed to yield identical IGF-I and IGF-II concentrations in the two pools. Western ligand and immunoblotting gave the characteristic IGFBP patterns for the two types of serum. Both pools dose-dependently stimulated DNA synthesis in cultured chick embryo fibroblasts. Stimulation by pregnancy serum was twice that by normal serum at 0.05-0.2% concentrations (P < 0.001). In the presence of excess monoclonal anti-IGF-I and -II antibodies, stimulation by both (0.1-0.2%) pools was 70-80% reduced and residual stimulation was similar. Addition of recombinant human (rh) IGFBP-3 dose-dependently depressed both pools' activity, more so for normal serum at 25 and 50 ng/ml, equally for each at 100 ng/ml. At the latter concentration, slight proteolysis of the rhIGFBP-3 was detectable in the presence of 0.2% pregnancy serum, but at 25 ng/ml, proteolysis was absent. These results suggest that IGFs are released more readily from pregnancy serum, accounting for the weaker inhibitory effect of low rhIGFBP-3 concentrations. For identical IGF concentrations, pregnancy serum's greater biological activity therefore reflects greater IGF availability to the cells. This study demonstrates the functional consequences at cellular level of serum IGFBP-3 proteolysis, underlining its significance in regulating serum IGF bioavailability.