tbuckley/cabot-search huggingface dataset:
Carrier-mediated uptake and excretion of bromosulfophthalein-glutathione in perfused rat liver: A multiple indicator dilution study*1, *2
Authors: W PINGGENG
Journal: Hepatology (1995)

The hepatic removal of the glutathione conjugate of bromosulfophthalein (BSPGSH) was studied in the single-pass perfused rat liver with the multiple indicator dilution (MID) technique against various background concentrations of BSPGSH (20 to 214 μmol/L) over which nonlinear binding to both plasma (albumin) and tissue proteins with two classes of binding sites was found. A bolus containing 51Cr-labeled red blood cell (a vascular reference), [125I]albumin and [14C]sucrose (large and small molecular weight interstitial references, respectively), D2O (a cellular space reference), and [3H]BSPGSH was injected into the portal vein during steady-state. The eliminated fraction of dose, obtained by subtracting the survival fraction of [3H]BSPGSH in plasma from one, corresponded to the steady state extraction ratio (E) with bulk data, which declined from 0.74 ± 0.04 to 0.27 ± 0.01 with concentration. The major portion of the tracer outflow profile was a throughput component, which is the proportion of tracer that did not enter liver cells during its transit through the liver. The influx, efflux, and sequestration coefficients, evaluated with previously developed barrier-limited models, provided the corresponding influx (k1), efflux (k−1) and excretion (kseq) rate constants. Concentration-dependent influx (Vmax = 83 μmol min−1 g−1 and Km = 3.7 μmol/L), efflux (Vmax = 15 μmol min1 g−1 and Km = 1.8 μmol/L), and excretion (Vmax = 94 μmol min1 g−1 and Km = 1.8 μmol/L) were obtained for BSPGSH, when Km values are expressed in terms of the unbound concentrations. In these calculations, the observed unbound tissue concentration was not used for estimation of the Vmax and Km for efflux and excretion because of overestimation, because of the presence of highly concentrated BSPGSH in ductular elements present in liver homogenates; rather, the unbound tissue concentration was calculated from the influx, efflux, and removal rate coefficients. Because of carrier-mediated entry, the unbound tissue concentration does not equal the unbound plasma concentration, and kinetic parameters for BSPGSH excretion could be alternately estimated when the rate of excretion or net rate of loss of BSPGSH from plasma was regressed against the estimated tissue unbound concentration. This yielded a Vmax of 97 μmol min−1g−1 and a Km of 3.6 μmol/ L, values similar to those obtained from MID. Regression of rates of biliary excretion or net plasma disappearance against the logarithmic average unbound concentration, however, yielded a Vmax of 50 μmol min-1g−1 and a Km of 3.3 to 3.6 μmol/L, values which were, as expected, different from those obtained with MID for either influx, efflux, or removal. It was found that intracellular BSPGSH levels had not increased sufficiently enough to saturate efflux and excretion, and the limiting feature of the transfer process at high- bulk concentration of BSPGSH appeared to be the influx process.
Abstract 2900: Redox nanoparticle enhances effect of anticancer chemotherapy and suppresses cardio-toxicity
Authors: Yukio Nagasaki, Yuki Ozaki, Toru Yoshitomi
Journal: Cancer Research (2012)

Abstract Utilizing the self-assembled core-shell-type polymeric micelle technique, high-performance nanoparticles possessing stable nitroxide radicals in the core and reactive groups on the periphery were prepared (Nitroxide Radical-containing Nanoparticles; RNP). The average diameter of the nanoparticles was ca. 40 nm, and the nanoparticles emitted intense electron paramagnetic resonance (EPR) signals. Owing to the confinement of the nitroxide groups in the core of the nanoparticles, it reduces its toxicity, prolongs its blood circulation time. Under the low pH environment in vivo, it was confirmed that RNP disintegrated to expose the nitroxide radicals outside of the particle. It is sharp contrast against low-molecular-weight TEMPOL, which was reduced and excreted rapidly from the blood stream. Recently, we have reported that RNP is effectively worked to cerebral ischemia reperfusion injury. The RNP disintegrates in penumbra area due to the acidosis of ischemic region, followed by the scavenging reactive oxygen species (ROS) generated in this area. This strategy could be applied to other ischemic injuries such as renal and myocardial infarction. Quite recently, we have found that scavenging of ROS in tumor region by RNP improves efficiency of anticancer drug, doxorubicin (DOX). For example, RNP administration prior to the DOX-injection remarkably improved its efficiency. When RNP was administered via mice tail veil, it accumulated in tumor due to the enhancement permeation and retention (EPR) effect. The accumulated RNP scavenged excessive generated ROS in tumor, which suppressed activation of transcription factors such as NF-κB. Such suppression of inflammation related transcription factors might increase effectiveness of anticancer drug such as doxorubicin (DOX). The RNP pre-administration also reduced its side effect. Actually, 25mg/kg intravenous administrations of RNP before and after the DOX-injection (20mg/kg) reduced significantly the lactate dehydrogenase (LDH) and the creatine phosphokinase (CPK) activity. Thus, the nanoparticle anti-oxidant treatment is promising as a new adjuvant for anti-cancer chemotherapy without severe side effect by anticancer drug. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2900. doi:1538-7445.AM2012-2900
Effect of Omega-3 Fatty Acids on Growth of a Rat Mammary Tumor2
Authors: Rashida A. Karmali, Jane Marsh, Charles Fuchs
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Effect of Omega-3 Fatty Acids on Growth of a Rat Mammary Tumor Get access Rashida A. Karmali, Rashida A. Karmali Search for other works by this author on: Oxford Academic PubMed Google Scholar Jane Marsh, Jane Marsh Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles Fuchs Charles Fuchs Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 73, Issue 2, August 1984, Pages 457–461, https://doi.org/10.1093/jnci/73.2.457 Published: 01 August 1984 Article history Received: 12 October 1983 Accepted: 30 March 1984 Published: 01 August 1984
CB-12 * LIPID DROPLET ACCUMULATION IN VON HIPPEL-LINDAU CNS HEMANGIOBLASTOMAS IS A MANIFESTATION OF HIF OVEREXPRESSION
Authors: G. Lobel, N. Edwards, M. Merrill
Journal: Neuro-Oncology (2014)

CNS hemangioblastomas (HBs) are a major manifestation of the Von Hippel-Lindau (VHL) inherited tumor syndrome. Loss of functional VHL protein results in constitutive upregulation of hypoxia-inducible factor (HIF) and its downstream targets (e.g. VEGF) in affected cell types. The HB tumor cell exhibits a characteristic histologic lipid-laden "foamy" appearance, the biological basis of which has not been examined. Lipid accumulation in cells is an organized process and involves specific proteins that assist in assembling newly synthesized lipids into protein-covered droplets. The most studied lipid droplet proteins belong to the PAT family, named for the first three members: perilipin, adipose differentiation-related protein, and 47-kDa tail-interacting protein, now referred to as perilipin (PLIN) 1, 2, and 3, respectively. Of these, only PLIN2 is a HIF target gene, consistent with our observation that PLIN2 in glioblastoma occurs only focally in perinecrotic/hypoxic areas. We hypothesized that PLIN2 would be strongly upregulated in HB tumor cells. Twenty-two VHL-associated hemangioblastomas were examined immunohistochemically for PLIN1, -2, and -3. PLIN1 was absent and PLIN3 was observed only occasionally in small focal patches. However, all 22 HBs stained positively and robustly for PLIN2, which clearly outlined the lipid droplets in almost all HB tumor cells. In many cases, these droplets had enlarged and appeared to occupy the entire cytoplasm of the tumor cell. Double immunofluorescence indicated PLIN2 presence in the tumor/stromal, but not endothelial, cell compartment of HBs, another observation consistent with PLIN2 upregulation via HIF. The widespread, intense, and selective expression of PLIN2 in HBs suggests that HIF, via PLIN2 overexpression, promotes the extensive lipid droplet accumulation characteristic of these tumors. The extent to which this distinctive upregulation of PLIN2 has ramifications for understanding the biology of these tumors, or might be exploited for diagnostic or therapeutic purposes, remains to be determined.
Comparison of High and Low Dosage Levels of<sup>131</sup>I in the Treatment of Thyrotoxicosis
Authors: Garrett A. Hagen, Robert P. Ouellette, Earle M. Chapman
Journal: New England Journal of Medicine (1967)

THE appearance of permanent hypothyroidism several years after treatment of thyrotoxicosis with radioactive iodine (131I) was pointed out in the review of Chapman and Maloof1 in 1955. Its steadily increasing occurrence during the passage of time was reported in 1961 by Beling and Einhorn.2 The data of Dunn and Chapman3 show that radioactive iodine hypothyroidism occurs in 25 per cent of patients two years after 131I, the rate steadily increasing to 40 per cent after ten years.3 More recently, Nofal, Beierwaltes and Patno4 reported permanent hypothyroidism in 45 per cent after two years, the figure reaching about 70 per . . .
Transmission of Systemic Transthyretin Amyloidosis by Means of Domino Liver Transplantation
Authors: Arie J. Stangou, Nigel D. Heaton, Philip N. Hawkins
Journal: New England Journal of Medicine (2005)

To the Editor: Familial amyloidotic polyneuropathy is a fatal autosomal dominant disease caused by amyloidogenic genetic variants of transthyretin. The liver is the predominant source of circulating transthyretin, and liver transplantation is the only treatment available for the disease.1 Livers explanted from patients with familial amyloidotic polyneuropathy contain only microscopic amyloid deposits in hilar vessels and nerves and are otherwise uninvolved. Since 1995, more than 300 such livers removed at transplantation have been used sequentially as donor grafts for recipients with liver cancer or end-stage liver disease, in so-called domino liver transplantation.2 We report here a case of systemic transthyretin . . .
Premature Rupture of the Fetal Membranes
Authors: Samuel Parry, Jerome F. Strauss
Journal: New England Journal of Medicine (1998)

The membranes surrounding the amniotic cavity are composed of the amnion and the chorion, which are closely adherent layers consisting of several cell types, including epithelial cells, mesenchymal cells, and trophoblast cells, embedded in a collagenous matrix. They retain amniotic fluid, secrete substances both into the amniotic fluid and toward the uterus, and guard the fetus against infection ascending the reproductive tract. The membranes normally rupture during labor. Premature rupture of the fetal membranes is defined as rupture of the membranes before the onset of labor.1 Premature rupture of the membranes occurring before 37 weeks' gestation is usually referred to . . .
SP0019 AGG-523: Aggrecanase-selective inhibitor for the treatment of osteoarthritis
Authors: K.E. Georgiadis
Journal: Annals of the Rheumatic Diseases (2013)

Osteoarthritis (OA) is the most common form of arthritis affecting nearly 27 million people in the United States. OA is caused by the loss of articular cartilage due to increased production of proteolytic enzymes such as matrix metalloproteinases (MMPs) and aggrecanases. Depletion of aggrecan is one of the earliest changes observed in osteoarthritis. Aggrecan is a chondroitin sulfate and keratan sulfate-bearing proteoglycan. Two cartilage aggrecanases, Aggrecanase 1 (ADAMTS4) and Aggrecanase 2 (ADAMTS5) cleave aggrecan within the interglobular domain between residues Glu<sup>373</sup> and Ala <sup>374</sup>. There are no disease-modifying therapies for the treatment of OA. The current study describes the chondroprotective effect of an oral aggrecanase-selective inhibitor (AGG-523) in a rat model of osteoarthritis and demonstrates that the significant protection, and lack of phenotypic alteration, observed with gene-deleted ADAMTS-5 and ADAMTS-4/5 mice, can also be observed with the use of a selective ADAMTS-4/5 inhibitor in the rat meniscal tear model of OA. This paradigm of selective ADAMTS-4/5 inhibition avoids the side-effects observed clinically and pre-clinically with broad-spectrum MMP inhibition. <h3>Disclosure of Interest</h3> K. Georgiadis Shareholder of: Pfizer, Employee of: Pfizer
Pollen From Genetically Modified Bt Maize Does Not Promote Allergic Responses In Mice
Authors: Monica Andreassen, Elena Rocca, Thomas Bøhn, Odd-Gunnar Wikmark, Johnnie Van den Berg, Martinus Lovik, Terje Traavik, Unni C. Nygaard
Journal: Journal of Allergy and Clinical Immunology (2014)
Abstract 1623: PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells.
Authors: Yuan Xue, Sharon Lim, Yunlong Yang, Zongwei Wang, Lasse Dahl Ejby Jensen, Eva–Maria Hedlund, Patrik Andersson, Masakiyo Sasahara, Ola Larsson, Dagmar Galter, Renhai Cao, Kayoko Hosaka, Yihai Cao
Journal: Cancer Research (2013)

Abstract PDGF signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-β+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO-specific antibody attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-β signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. Citation Format: Yuan Xue, Sharon Lim, Yunlong Yang, Zongwei Wang, Lasse Dahl Ejby Jensen, Eva–Maria Hedlund, Patrik Andersson, Masakiyo Sasahara, Ola Larsson, Dagmar Galter, Renhai Cao, Kayoko Hosaka, Yihai Cao. PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. [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 1623. doi:10.1158/1538-7445.AM2013-1623
The relationship between ultrasonic pulsatility index and proximal arterial stenosis in a canine model.
Authors: D H Evans, W W Barrie, M J Asher, S Bentley, P R Bell
Journal: Circulation Research (1980)

Although the ultrasonic pulsatility index (PI) is used as a test of arterial inflow, the relationship between proximal arterial stenosis and PI has not been fully evaluated. In a series of experiments on dogs, over 200 measurements of pressure, flow (using an indwelling electromagnetic flowmeter), and PI were made distal to implanted arterial stenoses of varying length (0.5--9 mm) and cross-sectional area (36--94% reduction in area). It was shown that, whereas the reduction of PI correlates broadly with stenosis severity, the scatter of results is wide for all but the tightest stenoses. This scatter is due at least in part to the variability of the vascular bed distal to the site of measurement.
Abstract 1052: RNAi-mediated mutual regulation of FGF-2 and its antisense gene, NUDT6, in C6 glioma cells.
Authors: Mark Baguma-Nibasheka, Paul R. Murphy
Journal: Cancer Research (2010)

Abstract Basic fibroblast growth factor (FGF-2) is a potent wide-spectrum antiapoptotic mitogen, and the dysregulation of its expression is associated with cell proliferation and immortalization in a wide variety of tumors. We have previously reported that FGF-2 and NUDT6, the product of its antisense gene, are co-localized and inversely expressed in C6 glioma cells, and that constitutive overexpression of NUDT6 suppresses cellular FGF-2 expression, nuclear translocation, and the resumption of cell cycles (Baguma-Nibasheka et al., Mol Cell Endocrinol, 267:127-136, 2007). For the current report, we investigated the role of the endogenous RNAi machinery in mediating the post-transcriptional effects of NUDT6 on FGF-2 expression. FGF-2 knockdown was accompanied by a significant (&amp;gt;3 fold) increase in NUDT6 mRNA, and vice versa. Similar converse effects were observed on the cognate protein levels, as assessed by confocal immunoflourescence, Western blotting, and flow cytometry, indicating that these two transcripts may be mutually regulatory. Remarkably, knockdown of either transcript reduced cell proliferation and inhibited S-phase re-entry following serum deprivation (Table 1), indicating that both FGF-2 and NUDT6 may be involved in the regulation of cell cycle progression. Supported by the CIHR and NSERC.Table 1.S-Phase Percentages1 of C6 Cells following Knockdown and G0 Arrest.Hours after Return to 10% FBS Medium0361224Control siRNA4.8 ± 0.516.8 ± 1.321.6 ± 1.822.4 ± 1.123.0 ± 1.5NUDT6 siRNA4.1 ± 0.510.6 ± 1.3*14.2 ± 1.6*16.7 ± 1.8*19.8 ± 0.8FGF-2 siRNA3.5 ± 0.55.9 ± 0.8*6.9 ± 1.2*11.2 ± 1.1*14.5 ± 1.0*1mean ± SEM. * = significantly different from control; p&amp;lt;0.05, n=3. 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 1052.
Congenital and Familial Iron Overload
Authors: L. Vitale, J. M. Opitz, N. T. Shahidi
Journal: New England Journal of Medicine (1969)

Two infants with hypotonia and minor congenital anomalies were found to have a striking increase in the total body iron in the absence of any hemolysis or unusual iron intake. The increase in iron was demonstrated histochemically and also by direct tissue iron determination. The absence of hemolysis and exogenous iron intake suggested a disturbance of iron transfer in utero. The presence of iron overload in both infants with similar clinical and pathological findings indicated that this condition is probably genetically determined.
Common bile duct stones: if you can’t sweep them, vacuum them!
Authors: Amol Sharma, Abraham Mathew
Journal: Endoscopy (2015)

Stone extraction from markedly dilated extrahepatic bile ducts can be challenging because of difficulty in achieving effective balloon apposition with the ductal wall. Studies examining stone extraction strategies in such cases are lacking. We describe this scenario in three patients and report a novel technique to overcome this technical difficulty.
1375 BARIATRIC SURGERY REDUCES ADIPOCYTE SIZE, IMPROVES LIVER INJURY AND COUNTERACTS LIPOTOXICITY VIA CHANGES IN SERUM FATTY ACID COMPOSITION AND ADIPONECTIN LEVELS
Authors: A. Wree, L.P. Bechmann, T. Claudel, M. Schlattjan, J.-P. Sowa, H. Baba, G. Gerken, A. Feldstein, M. Trauner, A. Canbay
Journal: Journal of Hepatology (2013)
S61 Cigarette smoke promotes polymerisation of Z 1-antitrypsin
Authors: S. Alam, Z. Li, S. Janciauskiene, R. Mahadeva
Journal: Thorax (2010)

Alpha-1 antitrypsin (AT) is an important inhibitor of neutrophil elastase (NE). Z antitrypsin (Glu342Lys) (Z-AT) polymerises within the hepatocyte and the subsequent severe plasma deficiency exposes the lungs to uncontrolled elastolysis and premature emphysema. We have shown that polymeric Z-AT (pZ-AT) are found in emphysematous alveolar walls and are co-localised with neutrophils. pZ-AT does not inhibit NE and are also pro-inflammatory and chemotactic to neutrophils, suggesting a novel role for pZ-AT in Z-AT related emphysema. Cigarette smoking (CS) accelerates decline in lung function in Z-AT homozygotes, but the mechanism involved in this is unknown. We investigated whether CS exposure would induce formation of pZ-AT. Female transgenic mice for human M-AT and Z-AT were exposed to four 1R3F research cigarettes daily for 5 days. BALF and perfused lungs were subsequently collected. Concentrations of pAT and oxidised AT were assessed by ELISA and immunoblot. Neutrophil numbers were assessed by quantifying stained cytospins and neutrophil elastase activity of lung homogenates (LH). pAT was undetectable in non-CS Z or CS-M mice. Polymeric AT was markedly increased in BALF and LH in CS-Z mice; BALF CS-Z 141(146–114) ng/ml; p=0.001 and LH, 232.5(241.1–218.6) ng/lung, p=0.001. Immunoblot of BALF demonstrated the classical ladders of pATin CS-Z mice.BALF and LH of CS-Z mice had higher neutrophil numbers compared with CS-M mice; NE LH, CS-Z 49(50–45) ng/lung vs CS-M mice 21(25–18); p&lt;0.001. Neutrophil numbers in the lung were tightly correlated with polymer concentrations; correlation coefficient, r<sup>2</sup>=0.93; p=&lt;0.001. Incubation of plasma purified Z-AT with CS extract (CSE) demonstrated that CSE oxidises Z-AT leading to an accelerated rate of polymerisation; CSE+Z, 114.4 nM/h, Z control 10.3; p&lt;0.001. This was confirmed by the finding that CS-induced polymerisation could be abolished by the antioxidant N-acetyl cysteine CSE+NAC+Z-AT 13.3; p=0.135 vs control. In conclusion, acute CS exposure directly promotes polymerisation of Z-AT via oxidation. The production of pZ-AT further reduces the anti-proteinase protection and attracts neutrophils potentially hastening lung damage. These novel findings provide a molecular explanation for the striking association of premature emphysema in ZZ homozygotes who smoke.