Biomedical subjects

Huan Tran

Publications and source records attributed to Huan Tran.

4 recordsLinked to original sources

PubMed2004

Functional integrity of intravenous immunoglobulin following irradiation with a virucidal dose of gamma radiation.

Although intravenous immunoglobulins (IVIG) and other plasma therapeutics have had a relatively good safety record, improved methods for viral clearance are constantly being evaluated and incorporated into new manufacturing processes. Gamma irradiation has been used routinely to assure sterility of healthcare products and medical devices, but it has not been applied successfully as a viral inactivation method for biologics. We examine whether virucidal doses of gamma irradiation (50 kGy) can be delivered to a manufacturing intermediate form of IVIG, a fractionated plasma paste, with negligible effect on structural and functional integrity of purified IgG product. Immunoglobulins from paste were examined for radiation-induced damage by SDS-PAGE and ELISAs utilizing viral antigens specific for rubella, CMV and mumps. Fc domain integrity was assessed by immunoblotting, quantitatively comparing the binding of irradiated and non-irradiated materials to cell surface Fcgamma receptors, and by employing quantitative RT-PCR to study the kinetics of accumulation of mRNA for the immune modulatory cytokines IL-1alpha, IL-1beta, IL-4, IL-8, IFNgamma, and TNFalpha. The results demonstrate that Fab and Fc domains of IVIG remain essentially intact and functional after gamma irradiation to virucidal doses, suggesting that this method could be used to enhance the safety of IVIG products.

Antigens↗

PubMed2004

Ocular oxygen consumption: estimates using vitreoperfusion in the cat.

PURPOSE: Little is known about the ocular oxygen consumption rate (QO2) in human diseases. Alterations in QO2 must occur in many conditions, such as retinal ischemia. We present a method of estimating QO2 that eventually could be used in patients during vitrectomy surgery. METHODS: We performed vitreoperfusion (i.e., perfusion of the vitreous cavity after vitrectomy) in 14 cat eyes with no ocular blood flow. The solution contained nutrients at a high partial pressure of oxygen (PO2). In eight eyes, the retinas were undisturbed (Group 1), and in six eyes, we excised the retinas (Group 2). We estimated QO2 in both groups on the basis of the temporal decline of PO2 in the vitreoperfusion solution according to a pharmacokinetic model. RESULTS: The mean and standard deviation of QO2 was 3.2 +/- 0.8 microL/min in Group 1 and 0.4+/- 0.7 microL/min in Group 2, with the difference being the retinal contribution, 88%. In Group 1, metabolism, bulk flow, and diffusion accounted for 82, 13, and 5%, respectively, of the oxygen loss from the vitreoperfusion solution. CONCLUSION: We estimated ocular oxygen consumption by means of vitreoperfusion. Eventually, the pathophysiology of human diseases may be clarified by similar measurements during vitrectomy.

Animals↗

PubMed2003

Modulation of the LDL receptor and LRP levels by HIV protease inhibitors.

Inhibitors of the human immunodeficiency virus (HIV)-1 protease have proven to be effective antiretroviral drugs. However, patients receiving these drugs develop serious metabolic abnormalities, including hypercholesterolemia. The objective of the present study was to identify mechanisms by which HIV protease inhibitors increase plasma cholesterol levels. We hypothesized that HIV protease inhibitors may affect gene regulation of certain LDL receptor (LDLR) family members, thereby altering the catabolism of cholesterol-containing lipoproteins. In this present study we investigated the effect of several HIV protease inhibitors (ABT-378, Amprenavir, Indinavir, Nelfinavir, Ritonavir, and Saquinavir) on mRNA, protein, and functional levels of LDLR family members. Our results demonstrate that one of these drugs, Nelfinavir, significantly decreases LDLR and LDLR-related protein (LRP) mRNA and protein levels, resulting in the reduced functional activity of these two receptors. Nelfinavir exerts its effect by reducing levels of active SREBP1 in the nucleus. The finding that Nelfinavir reduces the levels of two key receptors (LRP and LDLR) involved in lipoprotein catabolism and maintenance of vessel wall integrity identifies a mechanism that causes hypercholesterolemia complications in HIV patients treated with this drug and raises concerns about the atherogenic nature of Nelfinavir.

Anti-HIV Agents↗

PubMed2002

Integrin clustering induces kinectin accumulation.

Integrin receptors mediate the formation of adhesion complexes and play important roles in signal transduction from the extracellular matrix. Integrin-based adhesion complexes (IAC) contain proteins that link integrins to the cytoskeleton and recruit signaling molecules, including vinculin, paxillin, focal adhesion kinase, talin and alpha-actinin. In this study, we describe a approximately 160 kDa protein that is markedly enriched at IAC induced by clustering integrins with fibronectin-coated beads. Protein sequence analysis reveals that this approximately 160 kDa protein is kinectin. Kinectin is an integral membrane protein found in endoplasmic reticulum, and it serves as a receptor for the motor protein kinesin. Fibronectin-induced IAC sequestered over half of the total cellular content of kinectin within 20 minutes. In addition, two other ER-resident proteins, RAP [low-density lipoprotein receptor-related protein (LRP) receptor-associated protein] and calreticulin, were found to be clustered at IAC, whereas kinesin was not. Our results identify a novel class of constituents of IAC.

Amino Acid Sequence↗