Anecdotal reports have suggested that transplantation of hepatitis C virus (HCV) antibody positive (Ab+)/nucleic acid test negative (NAT-) donor kidneys into HCV negative recipients is not associated with HCV transmission. We reviewed our center's outcomes of 32 HCV negative patients who received kidney allografts from 25 donors who were HCV Ab+/NAT-. The mean recipient age was 56.9 ± 12.1 years and the mean donor age was 41.5 ± 14 years, with a median Kidney Donor Profile Index (KDPI) of 68%. Twelve donors (48%) met Public Health Service (PHS) increased risk status. All patients received antithymocyte globulin induction followed by tacrolimus, mycophenolate mofetil, and steroid maintenance immunosuppression. With a mean follow-up posttransplant of 10 ± 2.7 months, 1- and 3- month serum creatinine levels were 1.7 ± 0.8 and 1.3 ± 0.4, respectively, and patient and graft survival rates were 100% and 97%, respectively. Fourteen patients (44%) seroconverted and became HCV Ab+ posttransplant. However, all 32 patients were HCV RNA negative at 1- and 3- months posttransplant, and 27 and 8 patients tested at 6- and 12-months posttransplant, respectively, remain HCV RNA negative. In conclusion, transplantation of HCV Ab+/NAT- kidneys to HCV negative recipients frequently causes HCV Ab seroconversion but not HCV viremia.
Quinolinic acid (QA), a biologically potent but neurodestructive metabolite is catabolized by quinolinic acid phosphoribosyltransferase (QPRT) in the first step of the de novo NAD(+) biosynthesis pathway. This puts QPRT at the junction of two different pathways, that is, de novo NAD(+) biosynthesis and the kynurenine pathway of tryptophan degradation. Thus, QPRT is an important enzyme in terms of its biological impact and its potential as a therapeutic target. Here, we report the crystal structure of human QPRT bound to its inhibitor phthalic acid (PHT) and kinetic analysis of PHT inhibition of human QPRT. This structure, determined at 2.55 Å resolution, shows an elaborate hydrogen bonding network that helps in recognition of PHT and consequently its substrate QA. In addition to this hydrogen bonding network, we observe extensive van der Waals contacts with the PHT ring that might be important for correctly orientating the substrate QA during catalysis. Moreover, our crystal form allows us to observe an intact hexamer in both the apo- and PHT-bound forms in the same crystal system, which provides a direct comparison of unique subunit interfaces formed in hexameric human QPRT. We call these interfaces "nondimeric interfaces" to distinguish them from the typical dimeric interfaces observed in all QPRTs. We observe significant changes in the nondimeric interfaces in the QPRT hexamer upon binding PHT. Thus, the new structural and functional features of this enzyme we describe here will aid in understanding the function of hexameric QPRTs, which includes all eukaryotic and select prokaryotic QPRTs.
Background: Plasmablastic lymphoma (PBL) is a rare, highly aggressive lymphoma of plasma cell differentiation. It commonly presents as an Epstein-Barr virus (EBV)+ oral lesion in an immunodeficient patient, predominately human immunodeficiency virus (HIV)+ patients. These aggressive lesions often demonstrate an immunoblastic or plasmablastic morphology with a typical immunohistochemical profile.The current case is unique due to the location at presentation, immunohistochemical features, and unknown presence of HIV infection in a young adult male.Case Presentation: We present an unexpected case of PBL found in a rare extra-oral location in a young adult male with undiagnosed HIV infection presenting as a perianal hemorrhoid mass/abscess. Swift treatment for HIV and the PBL resulted in complete remission and markedly improved CD4 counts.Conclusions: This case highlights the importance of testing for HIV along with acquiring a thorough social/clinical history when a PBL is encountered. Although the overall prognosis of PBL is dismal with a median survival of about 6-11 months, a timely accurate diagnosis and prompt chemotherapy with an appropriate regimen along with antiretroviral therapy (ART) may still achieve a successful outcome with a relatively reasonable long-term remission like in our reported case.
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