Department of Pediatrics: Faculty Research and Presentationshttp://hdl.handle.net/10675.2/8382024-03-16T14:13:17Z2024-03-16T14:13:17ZNon-invasive Biomarkers to Detect Acute Kidney Injury in Premature InfantsMarin, TerriWilliams, BryanBhatia, JatindaSharma, AshokMundy, CynthiaCockfield, Christyhttp://hdl.handle.net/10675.2/6222502023-05-12T17:58:43ZNon-invasive Biomarkers to Detect Acute Kidney Injury in Premature Infants
Marin, Terri; Williams, Bryan; Bhatia, Jatinda; Sharma, Ashok; Mundy, Cynthia; Cockfield, Christy
Acute kidney injury (AKI) occurs in approximately 40% of preterm infants born ≤ 34 weeks’ gestational age (GA), many of whom become hypotensive. This condition can injure the kidney and is both difficult to detect and treat. The immature kidney only receives 3-4% of total cardiac output under optimal conditions (vs. 20% in term infants); hence, mild reductions in perfusion secondary to hypotension may quickly result in renal ischemia. Once AKI develops, mortality rates increase to >50%. Current diagnostic criteria (serial serum creatinine measures) does not detect early, subclinical injury, as up to 50% of renal function is lost by the time this method detects AKI. We sought to determine the feasibility of non-invasive physiologic biomarkers to detect early, subclinical AKI in premature infants ≤ 34 weeks’ gestation during the first 14 days of life (DOL). We hypothesized that an inverse relationship exists between renal hypoxia and urinary biomarkers when ischemic renal injury is present.
Characterization of a high-affinity, highly selective tryptophan transport system in the human macrophage and the effects of overexpression of tryptophanyl t-RNA synthetase on Jurkat proliferationSeymour, Robert L.http://hdl.handle.net/10675.2/5752112020-08-11T15:04:15Z2004-04-01T00:00:00ZCharacterization of a high-affinity, highly selective tryptophan transport system in the human macrophage and the effects of overexpression of tryptophanyl t-RNA synthetase on Jurkat proliferation
Seymour, Robert L.
Suppression of T cell activation by macrophages/dendritic cells via tryptophan degradation has been shown to play an important role in immunotolerance. Tryptophan degradation is carried out by the enzyme indolamine-2,3-dioxegenase (IDO). This model raises many questions. This study addresses two of these questions. First, how does the macrophage gain access to and degrade tryptophan to a level below 50 nM in culture medium? This is achieved despite the fact that the known high affinity tryptophan transport systems accept other amino acids and have Km values for tryptophan ranging fi-om 10-100 pM. In this study we show that the macrophage possesses a high-affinity, highly selective, and Na-independent tryptophan transport system with a Km for tryptophan of about 300 nM. This would allow the macrophage to have effective access to tryptophan at concentrations in the nanomolar range. We also show T cells do not possess this transport system. Second, how does the T cell sense the level of intracellular free tryptophan? It has been shown in the past that if T cells are stimulated in medium containing less than SOOnM tryptophan that they attempt to activate but arrest in mid-Gl of the cell cycle. The enzyme tryptophanyl t-RNA S5mthetase (WRS) charges tRNA*'^ with tryptophan. This enzjmie has two protein isoforms, with one having a non-canonical N-terminal kinase domain. WRS is also upregulated by interferon gamma (IFNy). These characteristics put WRS in a position to be an intracellular free tryptophan sensor. Here we show that transient transfection of the T cell line, Jurkat, with cDNA encoding the kinase-containing isoform of WRS inhibits proliferation. In addition, to the above we have ereated a subline of Jurkat, which stably arrests in the absence of tryptophan. We also show that this new subline is resistant to the drug G418 but is sensitive to hygromycin. When treated with rapamycin the Jurkat sub line will stably arrest in the presence or absence of tryptophan. Rapamycin is a known immunosuppressive agent, which inhibits T cell proliferation. This leads to the speculation of a possible link between the signaling pathways involved in tryptophan sensing and those involved in the effects of rapamycin.
2004-04-01T00:00:00ZNovel Therapeutic Approaches to Leishmania InfectionMakala, Levi HCBaban, Babakhttp://hdl.handle.net/10675.2/3159682019-08-30T07:15:00Z2014-03-19T00:00:00ZNovel Therapeutic Approaches to Leishmania Infection
Makala, Levi HC; Baban, Babak
Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Approximately 1.2 million cases of cutaneous leishmaniasis (CL) and 500,000 cases of visceral leishmaniasis (VL), which is lethal if untreated, occur annually across the globe as per world health organization (WHO) estimates [1-3]. Current statistics and information relevant to leishmaniasis are summarized in Table 1. Leishmaniasis currently affects about 12 million people and it is estimated that approximately 350 million people live in risk of infection [1-3].The number of cases of leishmaniasis is probably underestimated because only 40 of the 88 countries where diseases frequently occur report them on a regular basis [4]. Leishmaniasis, is caused by several leishmania spp., that are obligate intracellular and unicellular kinetoplastid protozoan flagellate that establish themselves within the phagolysosome of host immune competent cells, especially macrophages and dendritic cells (DCs). In 1903, W.B. Leishman and C. Donovan reported this new parasite at the turn of the century [5,6]. Ronald Ross christened the new genus leishmania and the new species donovani in year 1903 [7]. L. major infection (leishmaniasis) in mice is a widely used model of human infection that has yielded critical insights into the immunobiology of leishmaniasis [8-10]. Leishmaniasis as a parasitic disease manifests itself mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL), of which VL is the most severe form of the disease. VL is lethal if untreated and spontaneous cure is extremely rare. Cutaneous leishmaniasis usually has milder course and often results into a self-healing of ulcers. Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, specifically the activation of targeted T-cell populations for appropriate cytokine production and activation of macrophages. L. major infection of B6 and BALB/c mouse strains drives predominantly TH1 and TH2 responses, respectively [11-14]. In murine model, the development of Th1 response is associated with control of infection, and Th2 response is associated with disease progression. However, Th1 and Th2 dichotomy in the human system is not as distinct as in mice and the murine model does not strictly apply to human leishmaniasis.
2014-03-19T00:00:00ZSickle Cell Disease: Genetics, Cellular and Molecular Mechanisms, and TherapiesPace, Betty S.Ofori-Acquah, Solomon F.Peterson, Kenneth R.http://hdl.handle.net/10675.2/8232019-08-30T07:12:47Z2012-08-22T00:00:00ZSickle Cell Disease: Genetics, Cellular and Molecular Mechanisms, and Therapies
Pace, Betty S.; Ofori-Acquah, Solomon F.; Peterson, Kenneth R.
2012-08-22T00:00:00Z