tbuckley/cabot-search huggingface dataset:
Effect of Thrombin Fragment (TP508) on Myocardial Ischemia Reperfusion Injury in a Model of Type 1 Diabetes Mellitus
Authors: Louis M. Chu, Robert M. Osipov, Michael P. Robich, Jun Feng, Michael R. Sheller, Frank W. Sellke
Journal: Circulation (2010)

Background— We investigated the efficacy of novel thrombin fragment TP508 on ischemia-reperfusion injury using a porcine model of type 1 diabetes mellitus. Methods and Results— Alloxan-induced diabetic male Yucatan swine underwent 60 minutes of mid-left anterior descending coronary artery occlusion, followed by 120 minutes of reperfusion. Fifty minutes into ischemia, animals received either placebo (DM; n=8) or TP508 as a bolus of 1 mg/kg followed by infusion at 2.5 mg/kg per hour (DMT; n=8). Hemodynamic parameters and myocardial function were monitored. Monastryl blue/triphenyl tetrazolium chloride staining was used to assess sizes of the areas at risk and infarction. Coronary microvascular reactivity was measured and expression of cell survival and proapoptotic proteins quantified. Preoperative serum glucose values were similar between groups (309±57 mg/dL in DM versus 318±67 mg/dL in DMT; P =0.92). Infarct size was smaller in the TP508-treated group (5.3±1.9% in DMT versus 19.4±5.6% in DM; P =0.03). There was no statistically significant difference in global or regional left ventricular function between groups. Endothelium-dependent microvessel relaxation was moderately improved in the DMT group ( P =0.09), whereas endothelium-independent relaxation was similar between groups. The expression of cell survival proteins Akt, phospho-p38, and mammalian target of rapamycin was higher in the areas at risk of DMT animals compared with DM animals ( P &lt;0.05), and expressions of proapoptotic glycogen synthase kinase 3β and caspase 3 were lower in the DMT group ( P &lt;0.05). Conclusions— This study demonstrates that, in type 1 diabetic swine, TP508 reduces infarct size after ischemia-reperfusion. Thus, TP508 may offer a novel approach in cardioprotection from ischemia-reperfusion injury in diabetic patients.
Gastrointestinal bleeding from gastric metastasis of renal cell carcinoma, treated by endoscopic polypectomy
Authors: A. Pezzoli, V. Matarese, S. Boccia, L. Simone, S. Gullini
Journal: Endoscopy (2007)

Metastatic tumors of the stomach are very rare. We report here a case of successful endoscopic treatment of gastrointestinal hemorrhage from gastric metastases of a renal cell carcinoma (RCC), 5 years after radical resection.
Elevated and sustained expression of the transcription factors Egr1 and Egr2 controls NKT lineage differentiation in response to TCR signaling
Authors: Michael P Seiler, Rebecca Mathew, Megan K Liszewski, Chauncey J Spooner, Kenneth Barr, Fanyong Meng, Harinder Singh, Albert Bendelac
Journal: Nature Immunology (2012)
The use of 1% pimecrolimus cream for the treatment of steroid-induced rosacea
Authors: C-Y. Chu
Journal: British Journal of Dermatology (2005)

Journal Article The use of 1% pimecrolimus cream for the treatment of steroid‐induced rosacea Get access C‐Y. Chu C‐Y. Chu Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung‐Shan South Road, Taipei 100, Taiwan E‐mail: chiayuju@seed.net.tw Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 2, 1 February 2005, Pages 396–399, https://doi.org/10.1111/j.1365-2133.2005.06404.x Published: 01 February 2005
Cystathionine gamma-lyase deficiency and overproliferation of smooth muscle cells
Authors: Guangdong Yang, Lingyun Wu, Sean Bryan, Neelam Khaper, Sarathi Mani, Rui Wang
Journal: Cardiovascular Research (2010)

AimsCystathionine gamma-lyase (CSE)-derived H2S plays an important role in regulating cell growth. Lack of CSE expression results in development of hypertension. The current study compared proliferation of smooth muscle cells derived from CSE gene knockout mice (SMCs-KO) with that of wild-type mice (SMCs-WT).
Serum from patients with fulminant hepatic failure causes hepatocyte detachment and apoptosis by a β1-integrin pathway
Authors: Philip N. Newsome, John Tsiaoussis, Steven Masson, Robert Buttery, Cameron Livingston, Ian Ansell, James A. Ross, Tariq Sethi, Peter C. Hayes, John N. Plevris
Journal: Hepatology (2004)

Hepatocyte transplantation is restricted by the impaired ability of hepatocytes to engraft and survive in the damaged liver. Understanding the mechanisms that control this process will permit the development of strategies to improve engraftment. We studied changes in liver matrix during acute injury and delineated the mechanisms that perturb the successful adhesion and engraftment of hepatocytes. Collagen IV expression was increased in sinusoidal endothelium and portal tracts of fulminant hepatic failure explants, whereas there were minimal changes in the expression of fibronectin, tenascin, and laminin. Using an in vitro model of cellular adhesion, hepatocytes were cultured on collagen-coated plates and exposed to serum from patients with liver injury to ascertain their subsequent adhesion and survival. There was a rapid, temporally progressive decrease in the adhesive properties of hepatocytes exposed to such serum that occurred within 4 hours of exposure. Loss of activity of the β1-integrin receptor, which controls adhesion to collagen, was seen to precede this loss of adhesive ability. Addition of the β1-integrin activating antibody (TS2/16) to cells cultured with liver injury serum significantly increased their adhesion to collagen, and prevented significant apoptosis. In conclusion , we have identified an important mechanism that underpins the failure of infused hepatocytes to engraft and survive in liver injury. Pretreating cells with an activating antibody can improve their engraftment and survival, indicating that serum from patients with liver injury exerts a defined nontoxic biological effect. This finding has important implications in the future of cellular transplantation for liver and other organ diseases. (Hepatology 2004;40:636-645.)
Direct evidence for binding of CD8 to HLA class I antigens.
Authors: Y Rosenstein, S Ratnofsky, S J Burakoff, S H Herrmann
Journal: The Journal of Experimental Medicine (1989)

Adhesion of T lymphocytes is an essential step for antigen recognition and lymphocyte activation. mAbs to T cell surface proteins have been used to define the receptor-ligand proteins that appear to be involved in adhesion. Since most assays measure the effects of mAbs on T lymphocyte function, it is not known whether mAb-mediated blocking is due to a disruption of receptor-ligand interactions or results in inhibition of some aspect of receptor-mediated triggering. It has been suggested that the CD8 molecule augments T cell avidity for the target cells by binding to determinants on target cell MHC class I molecules. In the present report, we demonstrated that purified CD8 molecules incorporated into large lipid vesicles (artificial target cells) mediate the adhesion of these vesicles to cells expressing HLA proteins, while vesicles expressing purified HLA class I antigens bind to CD8+ T cells. Furthermore, vesicles bearing CD8 will form conjugates with vesicles expressing HLA class I proteins. These conjugates were found to be specifically inhibited by mAbs to CD8 or HLA class I molecules. We also demonstrate that CD2-reconstituted vesicles can form conjugates with vesicles bearing LFA-3. These experiments provide direct evidence for an interaction of the CD8 molecule with class I MHC proteins as well as between CD2 proteins and LFA-3 proteins, thus supporting the hypothesis that these molecules can mediate cell-cell adhesion.
Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxy-amino acids into glycolaldehyde, 2-hydroxypropanal, and acrolein. A mechanism for the generation of highly reactive alpha-hydroxy and alpha,beta-unsaturated aldehydes by phagocytes at sites of inflammation.
Authors: M M Anderson, S L Hazen, F F Hsu, J W Heinecke
Journal: Journal of Clinical Investigation (1997)

Reactive aldehydes derived from reducing sugars and lipid peroxidation play a critical role in the formation of advanced glycation end (AGE) products and oxidative tissue damage. We have recently proposed another mechanism for aldehyde generation at sites of inflammation that involves myeloperoxidase, a heme enzyme secreted by activated phagocytes. We now demonstrate that human neutrophils employ the myeloperoxidase-H202-chloride system to produce alpha-hydroxy and alpha,beta-unsaturated aldehydes from hydroxy-amino acids in high yield. Identities of the aldehydes were established using mass spectrometry and high performance liquid chromatography. Activated neutrophils converted L-serine to glycolaldehyde, an alpha-hydroxyaldehyde which mediates protein cross-linking and formation of Nepsilon-(carboxymethyl)lysine, an AGE product. L-Threonine was similarly oxidized to 2-hydroxypropanal and its dehydration product, acrolein, an extremely reactive alpha,beta-unsaturated aldehyde which alkylates proteins and nucleic acids. Aldehyde generation required neutrophil activation and a free hydroxy-amino acid; it was inhibited by catalase and heme poisons, implicating H202 and myeloperoxidase in the cellular reaction. Aldehyde production by purified myeloperoxidase required H202 and chloride, and was mimicked by reagent hypochlorous acid (HOCl) in the absence of enzyme, suggesting that the reaction pathway involves a chlorinated intermediate. Collectively, these results indicate that the myeloperoxidase-H202-chloride system of phagocytes converts free hydroxy-amino acids into highly reactive alpha-hydroxy and alpha,beta-unsaturated aldehydes. The generation of glycolaldehyde, 2-hydroxypropanal, and acrolein by activated phagocytes may thus play a role in AGE product formation and tissue damage at sites of inflammation.
Frances birth rate matches high Irish levels
Authors: A. Dorozynski
Journal: BMJ (2002)

France is experiencing a minor baby boom for the second consecutive year, with 774 800 births recorded last year, the same number as in 2000, a new report from France's National Institute of Statistics and Economic Studies (INSEE) has shown.

The birth rate in France has also increased—from 1.88 children per woman of childbearing age in year 2000 to 1.89 last year.

“ “Such a birth rate for two consecutive years has not been observed for 20 years,” wrote Lionel Doisneau, the author of the study, which was released last week in Paris (www.insee.fr).

“Such a birth rate for two consecutive years has not been observed for 20 years,” wrote Lionel Doisneau, the …
The birth of poverty
Authors: R. Biswas
Journal: BMJ (2002)

Poverty was a young boy of 4 who met me in the streets of a busy city in India begging for money. I, nearly the same age, peered at him once and then took a guilty look at my ice cream. After that I learnt the trick of gulping ice creams without batting an eyelid while a million such children of an impoverished nation looked on, eyes gleaming with desire.

Many years have passed since then. In my medical career poverty has been a constant observer. In a country without an NHS, I have seen young people unable to afford a renal transplant dying in front of my eyes. Hospital policies in the premier institutes of India in which …
Fluid Loss in Peritoneal Dialysis
Authors: UMBERTO BUONCRISTIANI
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 June 1973Fluid Loss in Peritoneal DialysisUMBERTO BUONCRISTIANI, MARIO TIMIOUMBERTO BUONCRISTIANISearch for more papers by this author, MARIO TIMIOSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-6-981 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In reference to the article by Gault and associates, "Fluid and Electrolyte Complication of Peritoneal Dialysis" (1) and to the editorial note by Tenckhoff in the same issue (2), we would like to add some observations based on our experience of about 3000 peritoneal dialyses in the last 5 years.We disagree with Gault's suggestion of using 0.5% dextrose solutions to limit excess removal of fluid. In our experience solutions containing 1.5% dextrose and 140 meq/litre of Na+, with an exchange of 2.5 to 3 litres/hr (inflow and drainage speed), seldom caused excessive fluid loss requiring saline...References1. GAULT M, FERGUSON E, and SIDHU J: Fluid and electrolyte complications of peritoneal dialysis. Choice of dialysis solutions. Ann Intern Med 75:253-262, 1971 LinkGoogle Scholar2. TENCKHOFF H: Choice of peritoneal dialysis solutions. Ann Intern Med 75:313-314, 1971 LinkGoogle Scholar1. VIDT D: Recommendations on choice of peritoneal dialysis solutions. Ann Intern Med 78:144-146, 1973 LinkGoogle Scholar2. GAULT M: Peritoneal dialysis solutions. Can Med Assoc J 108:325-327, 1973 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: UMBERTO BUONCRISTIANI; MARIO TIMIOAffiliations: Institute of Patologia Medica University Policlinico of Perugia Perugia, Italy PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySilicon Carbide, SiC 1 June 1973Volume 78, Issue 6 Page: 981-982 Keywords Glucose Peritoneal dialysis ePublished: 1 December 2008 Issue Published: 1 June 1973 PDF downloadLoading ...
Ultrastructure of fibrillar granules in human neutrophils
Authors: Nobuo Takemori, Katsuyuki Hirai, Ryuichi Onodera, Nagahito Saito, Naoyuki Miyokawa
Journal: American Journal of Hematology (1994)

Abstract Fibrillar granules (FGs) represent neutrophilic primary granules containing clustered filaments. We investigated neutrophils in the bone marrow obtained from 17 patients with chronic myeloproliferative disorders (CMPD) by electron microscopy. FG‐positive neutrophils were seen in 15 of the 17 CMPDs with varying frequencies. The diameter of FG‐filaments was 7–8 nm, showing that they corresponded to neither intermediate filaments nor actin filaments. © 1994 Wiley‐Liss, Inc.
Somatic Mutations of Epidermal Growth Factor Receptor in Colorectal Carcinoma
Authors: Hisashi Nagahara, Koshi Mimori, Mitsuhiko Ohta, Tohru Utsunomiya, Hiroshi Inoue, Graham F. Barnard, Masaichi Ohira, Kosei Hirakawa, Masaki Mori
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non–small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA. Experimental Design: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA. Results: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma. Conclusions: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment.
MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-κB–dependent lymphoma
Authors: Michael A. Milhollen, Tary Traore, Jennifer Adams-Duffy, Michael P. Thomas, Allison J. Berger, Lenny Dang, Lawrence R. Dick, James J. Garnsey, Erik Koenig, Steven P. Langston, Mark Manfredi, Usha Narayanan, Mark Rolfe, Louis M. Staudt, Teresa A. Soucy, Jie Yu, Julie Zhang, Joseph B. Bolen, Peter G. Smith
Journal: Blood (2010)
Influence of Treatment Conforming to Guidelines on Recurrence Free Survival (RFS) and Overall Survival (OS) in Triple Negative Breast Cancer.
Authors: Z. Atassi, M. Wischnewsky, A. Wöckel, C. Kurzeder, R. Wolters, I. Novopashenny, R. Kreienberg
Journal: Cancer Research (2009)

Abstract Introduction: The triple negative(TN) breast cancer subtype (ER neg, PR neg, HER 2 neg) represents about 10 to 15% 0f all breast cancer types. It characterizes an aggressive phenotype with significantly worsened RFS, OS as well as specific clinical and pathological properties. The aim of this study was: 1.To assess the efficacy of guideline conforming conventional chemotherapy, local recurrence rate, distant recurrence rate, as well as overall survival. 2.To ask for subgroups that show the greatest benefit from conventional chemotherapy and 3. to ask for impact of guidelines violation on RFS and OA.Patients and methods: 3658 breast cancer Patients that were first diagnosed between the years 2000 and 2005 were analyzed in a multicentric retrospective study. A total of 371 (10,1%) were triple negative. Results: Median age was 62 years(26-101) TN: 60years.(28-97). 13,8% of all included patients are triple negative. 90,3% of all TN patients are at intermediate/high risk according to Nottingham risk classification. 76,5 have G3 tumors. The 5 year DFS is 74,8% (95%CI 68,8% - 80,8%) and for none TN 86,5%(95%CI 84,6% - 88,4%) (logrankp&amp;lt;0,0001). The 5 year OS is 75,8%(95%CI:69,9%- 81,8%) and for none TN 86%(95%CI:84,1%-87,9%). (logrank p &amp;lt; 0,0001). The essential parameters for RFS and OS were guidelines conforming surgery and radiation therapy, when chemotherapy conforming to guidelines was provided. The 5 year RFS for TN patients undergoing a 100% guideline according adjuvant therapy is 86.1%(95%CI:78.9%-93.4%), with 1-2 violations 76.0% (95%CI:69.0%-83.1%) and with ≥3 violations 50.6%(95%CI:20.1%-81.1%) (logrank p&amp;lt;0.0001). In total a 66,8% of all TN patients were not treated according to guidelines (ranking of violations: Chemotherapy, radiation therapy, surgery). 18% had 2 or more violations. Summary: The Results show a significant improvement of outcomes in TN breast cancer patients when treatment is conducted in accordance to guidelines. There are subgroups of TN breast cancer patients that profit from therapy according to guidelines. The leading guideline violation was noted for radiation therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2101.
Microstructural evolution of lipid aggregates in nucleating model and human biles visualized by cryogenic transmission electron microscopy
Authors: Fred M. Konikoff, Dganit Danino, Daphna Weihs, Moshe Rubin, Yeshayahu Talmon
Journal: Hepatology (2000)

Obtaining reliable information on the physical state and ultrastructure of bile is difficult because of its mixed aqueous-lipid composition and thermodynamic metastability. We have used time-lapse cryogenic transmission electron microscopy (cryo-TEM) combined with video-enhanced light microscopy (VELM) to study microstructural evolution in nucleating bile. A well-characterized model bile and gallbladder biles from cholesterol and pigment gallstone patients were studied sequentially during cholesterol nucleation and precipitation. In model bile, cholesterol crystallization was preceded by the appearance of the following distinct microstructures: spheroidal micelles (3-5 nm), discoidal membrane patches (50-150 nm) often in multiple layers (2-10), discs (50-100 nm), and unilamellar (50-200 nm) and larger multilamellar vesicles (MLVs). The membrane patches and discs appeared to be short-lived intermediates in a micelle-to-vesicle transition. Vesicular structures formed by growth and closure of patches as well as by budding off from vesicles with fewer bilayers. MLVs became more abundant, uniform, and concentric as a function of time. In native bile, all the above microstructures, except discoidal membrane patches, were observed. However, native MLVs were more uniform and concentric from the beginning. When cholesterol crystals appeared by light microscopy, MLVs were always detected by cryo-TEM. Edges of early cholesterol crystals were lined up with micelles and MLVs in a way suggesting an active role in feeding crystal growth from these microstructures. These findings, for the first time documented by cryo-TEM in human bile, provide a microstructural framework that can serve as a basis for investigation of specific factors that influence biliary cholesterol nucleation and crystal formation.
Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor.
Authors: E J Haskel, S R Torr, K C Day, M O Palmier, T C Wun, B E Sobel, D R Abendschein
Journal: Circulation (1991)

BACKGROUND This study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological inhibitor of tissue factor-induced coagulation mediated by the extrinsic pathway. METHODS AND RESULTS Thrombosis was induced in femoral arteries of anesthetized dogs with the use of anodal current to elicit extensive vascular injury and formation of platelet-rich thrombi in one artery and with thrombogenic copper wire to elicit fibrin-rich thrombi without appreciable vascular injury in the contralateral artery. Recanalization of both vessels was induced with t-PA (1.7 mg/kg i.v. over 1 hour) and verified with Doppler flow probes. Reocclusion occurred within 2 hours in seven of seven arteries with electrical injury-induced thrombosis and in four of seven arteries with copper wire-induced thrombosis in the absence of LACI. In dogs given infusions of recombinant DNA-produced LACI (225 micrograms/kg over 15 minutes, followed by 4 micrograms/kg/min i.v.) after completion of the infusion of t-PA, no reocclusion occurred during the 2-hour interval of observation in any of the five arteries subjected to electrical injury (p less than 0.001), and cyclic partial occlusions were nearly abolished (0.4 +/- 0.4/hr in LACI-treated dogs compared with 13.7 +/- 5.5/hr in saline-treated dogs, p less than 0.0001). In contrast, reocclusion occurred in two of five arteries with indwelling copper wires, and cyclic partial occlusions were unaffected despite LACI. LACI prolonged the partial thromboplastin time modestly (1.7 +/- 0.2 x baseline) but did not affect platelet counts or aggregation assessed ex vivo. CONCLUSIONS Inhibition of the extrinsic pathway of coagulation with LACI prevents thrombotic arterial reocclusion after thrombolysis in vessels subjected to extensive vascular injury. Our results demonstrate that activation of the extrinsic pathway plays a critical role in thrombotic reocclusion and that LACI provides a highly targeted approach to facilitate sustained recanalization without directly inhibiting platelets.