Eppley Institute for Research in Cancer and Allied Diseases

About: Eppley Institute for Research in Cancer and Allied Diseases is a based out in . It is known for research contribution in the topics: Pancreatic cancer & Cancer. The organization has 965 authors who have published 1396 publications receiving 58994 citations.

Hepatic JAK2 protects against atherosclerosis through circulating IGF-1

Abstract: Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2's essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection.

Calreticulin binds to the α1 domain of MHC class I independently of tapasin

Abstract: Prior to binding to antigenic peptide, the major histoconipatibility complex (MHC) heavy chain associates with an assembly complex of proteins that includes calreticulin, tapasin, and the transporter associated with antigen processing (TAP). Our data show that calreticulin can bind weakly to L-d without tapasin's assistance, and that deglycosylation of the alpha1 domain results in a primary loss of binding to calreticulin rather than tapasin. We have also shown that high amounts of wild-type tapasin are still unable to associate with MHC class I in the absence of the MHC class I/calreticulin interaction, confirming the central role of calreticulin in the formation of the MHC class I assembly complex.

Somatostatin infusion and hemodynamic changes in patients with non-variceal upper gastrointestinal bleeding: a pilot study.

Abstract: Background Intravenous somatostatin decreases acid secretion, splanchnic blood flow, and portal pressure, but the evidence for its efficacy in the treatment of non-variceal upper gastrointestinal bleeding has been mixed. We aimed to evaluate the vasoactive effect and possible mechanisms of somatostatin infusion in the cessation of non-variceal upper gastrointestinal bleeding. Material/methods Patients with non-variceal upper gastrointestinal bleeding without portal hypertension were enrolled in the study. They were given somatostatin infusion in a dose of 250 microgr/hour for 72 hours. Superior mesenteric arterial average flow velocity (SMA-V), SMA pulsatility index (SMA-PI), portal venous volume flow (PV-F), and renal artery resistance index (RA-RI) were measured two times for each patient by Doppler ultrasound; once on the first day of infusion therapy and again 6 hours or more after stopping the infusion. Results 21 patients (12 male, mean age 44.1 +/- 9.9) with bleeding peptic ulcer were enrolled. During somatostatin infusion, PV-F was 33.7 +/- 12.7 cm3/sec. After stopping infusion, it increased to 56.3 +/- 16.0 cm3/sec (p=0.001). SMA-V was 39.7 +/- 13.1 cm/sec and 64.4 +/- 15.1 cm/sec during somatostatin infusion and after cessation of somatostatin respectively (p=0.01). SMA-PI was 2.0 +/- 0.8 during somatostatin infusion but 2.8 +/- 0.8 without somatostatin infusion (p=0.02). However, RA-RI showed no difference between states with or without somatostatin infusion (p>0.05). Conclusions Somatostatin infusion causes a decrease in arterial blood flow to the stomach and duodenum in patients with non-variceal upper gastrointestinal bleeding without portal hypertension. Somatostatin therapy also decreases portal blood flow while not altering renal blood.

Tracking reflections through cryogenic cooling with topography

Abstract: The mosaic structure of a single protein crystal was analyzed by reflection profiling and topography using highly parallel and monochromatic synchrotron radiation. Fine-φ-sliced diffraction images (0.002° stills) were collected using a conventional large-area CCD detector in order to calculate reflection profiles. Fine-φ-sliced topographic data (0.002°) stills were collected with a digital topography system for three reflections in a region where the Lorentz effect was minimized. At room temperature, several different mosaic domains were clearly visible within the crystal. Without altering the crystal orientation, the crystal was cryogenically frozen (cryocooled) and the experiment was repeated for the same three reflections. Topographs at cryogenic temperatures reveal a significantly increased mosaicity, while the original domain structure is maintained. A model for the observed changes during cryocooling is presented.

Synthesis of an N-methyl-N-nitrosourea linked to a methidium chloride analogue and its reactions with 32P-end-labeled DNA

Abstract: The synthesis and characterization of an N-methyl-N-nitrosourea (MNU) analogue that is covalently linked to methidium nucleus (9) is described. At 37/degrees/C in pH 8.0 buffer 9 hydrolyzes via pseudo-first-order kinetics, with a calculated t/sub 1/2/ = 77 min. By use of polyacrylamide sequencing gels the formation of piperidine-labile N/sup 7/-methylguanine adducts from the reaction of 9 and MNU with 5'-/sup 32/P-end-labeled DNA restriction fragments is reported. DNA methylation by 9 in 10 mM Tris buffer is enhanced with increasing ionic strength (50-200 mM NaCl), which contrasts to the inhibition of MNU-induced cleavage with increasing salt. In addition, 9 methylates all G sites equally, while MNU shows a clear preference for d(G)/sub n/ (n greater than or equal to 3) runs and an asymmetrical methylation pattern within these G-rich regions. The results are discussed in terms of the delivery of the MNU moiety to the DNA target by a non-sequence-specific intercalation process and the subsequent hydrolytic generation of a nondiffusible alkylating intermediate.