University of Pittsburgh

About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.

The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion

Abstract: High-mobility group box 1 (HMGB1) is a nuclear factor that is released extracellularly as a late mediator of lethality in sepsis as well as after necrotic, but not apoptotic, death. Here we demonstrate that in contrast to the delayed role of HMGB1 in the systemic inflammation of sepsis, HMGB1 acts as an early mediator of inflammation and organ damage in hepatic ischemia reperfusion (I/R) injury. HMGB1 levels were increased during liver I/R as early as 1 h after reperfusion and then increased in a time-dependent manner up to 24 h. Inhibition of HMGB1 activity with neutralizing antibody significantly decreased liver damage after I/R, whereas administration of recombinant HMGB1 worsened I/R injury. Treatment with neutralizing antibody was associated with less phosphorylation of c-Jun NH2-terminal kinase and higher nuclear factor–κB DNA binding in the liver after I/R. Toll-like receptor 4 (TLR4)-defective (C3H/Hej) mice exhibited less damage in the hepatic I/R model than did wild-type (C3H/HeOuj) mice. Anti-HMGB1 antibody failed to provide protection in C3H/Hej mice, but successfully reduced damage in C3H/Ouj mice. Together, these results demonstrate that HMGB1 is an early mediator of injury and inflammation in liver I/R and implicates TLR4 as one of the receptors that is involved in the process.

Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination.

Abstract: A 'rescuable' plasmid containing globin gene sequences allowing recombination with homologous chromosomal sequences has enabled us to produce, score and clone mammalian cells with the plasmid integrated into the human beta-globin locus. The planned modification was achieved in about one per thousand transformed cells whether or not the target gene was expressed.

Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.

Abstract: Since the introduction of Laparoscopic Roux-en-Y gastric bypass (LRYGBP) in the early 1990s, several investigators have demonstrated that LRYGBP is as effective as open roux-en-Y gastric bypass (RYGBP) in achieving significant long-term weight loss (60–80% percent of excess body weight loss [%EWL]) in morbidly obese patients while significantly reducing perioperative morbidity and recovery time.1–5 In 2000, our group reported (n = 275 patients) a mean excess weight loss of 77% (mean body mass index [BMI] reduced from 48 to 27 kg/m2) at 30 months and a major morbidity and mortality rate of 3.3% and 0.4%, respectively.2 Quality of life was significantly improved and all obesity comorbidities, with the exception of depression, were significantly improved or resolved. Although that study did not focus specifically on type 2 diabetes mellitus (T2DM), we did find that 82% of T2DM patients (n = 18) achieved clinical resolution (withdrawal of all antidiabetic medication) whereas the remaining 18% had significant improvement. Other investigators have also demonstrated that not only Roux-en-Y gastric bypass but other bariatric operations may result in significant clinical improvement in T2DM after weight loss.2,5–13 However, little is known concerning the effect of weight loss surgery on the degree of glycemic control that is achieved and its impact on antidiabetic medication requirement. Furthermore, factors that may be associated with postoperative resolution versus improvement in diabetes have not been fully elucidated. The goal of this study then was to evaluate the effect of LRYGBP on morbidly obese patients with T2DM and their related comorbidites and diabetes-specific complications. Our hypothesis was that LRYGBP would result in sustained weight loss that would correspond to significant improvement in glycemic control, leading to clinical resolution or improvement in T2DM and related comorbidites and complications. We specifically evaluated postoperative outcomes, including surgical complications and weight loss as well as changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1C), diabetic medication requirement, and changes in comorbidity and diabetes complications.

Transcription of IAP endogenous retroviruses is constrained by cytosine methylation

Abstract: 116 nature genetics volume 20 october 1998 Berkeley, California 94720, USA. 2Department of Pathology, University of Washington, Seattle, Washington 98195, USA. 3Department of Radiation Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. Correspondence should be addressed to J.C. (e-mail: jcampisi@lbl.gov). 1. Martin, G.M. Birth Defects 14, 5−39 (1978). 2. Goto, M. Mech. Ageing Dev. 98, 239–254 (1997). 3. Martin, G.M., Sprague, C.A. & Epstein, C.J. Lab. Invest. 23, 86–92 (1970). 4. Salk, D., Bryant, E., Hoehn, H., Johnston, P. & Martin, G.M. Adv. Exp. Bio. Med. 190, 305–311 (1985). 5. Fukuchi, K., Martin, G.M. & Monnat, R.J. Proc. Natl Acad. Sci. USA 86, 5893–5897 (1989). 6. Cheng, R.Z., Murano, S., Kurz, B. & Shmookler-Reis, R.J. Mutat. Res. 237, 259–269 (1990). 7. Yu, C.E. et al. Science 272, 258–262 (1996). 8. German, J. Medicine 72, 393–406 (1993). 9. Main, I.S. Nucleic Acids Res. 25, 3187–3195 (1997). 10. Mushegian, A.R., Bassett, D.E. Jr, Boguski, M.S., Bork, P., & Koonin, E.V. Proc. Natl Acad. Sci. USA 94, 5831–5836 (1997). 11. Gray, M.D. et al. Nature Genet. 17, 100–103 (1997). 12. Linn, S.M., Lloyd, R.S. & Roberts, R.T. Nucleases (Cold Spring Harbor Laboratory Press, New York, 1993). 13. Yamagata, K. et al. Proc. Natl Acad. Sci. USA 95, 8733–8738 (1998). 14. Ogburn, C.E. et al. Hum. Genet. 101, 121–125 (1997). 15. Yan, H., Chen, C.-Y., Kobayashi, R. & Newport, J. Nature Genet. 19, 375–378 (1998).

Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors

Abstract: Importance Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer. Objective To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC. Design, Setting, and Participants International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. Main Outcomes and Measures Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria. Results Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP. Conclusions and Relevance Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.