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Jun Gao

Publications and source records attributed to Jun Gao.

At least 37 records · Page 2Linked to original sources
PubMed2006

Aberrant expression of PTCH (patched gene) and Smo (smoothened gene) in human pancreatic cancerous tissues and its association with hyperglycemia.

OBJECTIVES: To investigate the prevalence of PTCH (patched gene) and Smo (smoothened gene) expression in human pancreatic cancerous tissues and its association with clinical characteristics. METHODS: A rabbit polyclonal antibody against PTCH was prepared through the immunization of prokaryotic recombinant PTCH1170-1433 protein. The PTCH and Smo expression in 39 resected pancreas specimens from 28 patients with pancreatic cancer, 6 with chronic pancreatitis (as control), and 5 with pancreatic pseudocyst (as control) were detected by reverse transcriptase polymerase chain reaction and immunohistochemistry. The relationships between their expressions and pathological characteristics such as tumor sizes, degree of differentiation, nodal status, distant metastasis, and the blood sugar level were analyzed. RESULTS: The prevalence of PTCH and Smo expressions in cancerous tissues were 71.4% (20/28) and 53.6% (15/28), respectively, whereas no expression in the nontumor pancreas tissues was found. Both PTCH and Smo expressions correlated with the low levels of tumor tissue differentiation (P < 0.05) and PTCH and Smo expressions in islet cells of cancerous tissues associated with hyperglycemia. CONCLUSIONS: Because aberrant expressions of PTCH and Smo were common in human pancreatic carcinoma tissues and were associated with the low-level differentiation of tumor tissue and hyperglycemia, this indicated that these molecules played a fundamental role in pancreas tumorigenesis and were regarded as new targets for diagnosis and treatment of human pancreatic cancer.

Adult↗
PubMed2006

Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Glu and risk of breast cancer in Chinese women: a case control analysis.

Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are two major base excision repair (BER) proteins and act cooperatively in the BER processes. Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Gln may alter their protein functions and BER activity, and were therefore hypothesized to be associated with breast cancer susceptibility. We examined the contributions of these two polymorphisms to breast cancer susceptibility in a case-control study of 302 breast cancer cases, 221 patients with benign breast disease (BBD) and 639 cancer-free controls in a Chinese population. We found that the variant genotypes of both ADPRT Val762Ala and XRCC1 Arg399Gln were not significantly associated with the risk of breast cancer (adjusted OR 0.87, 95% CI 0.64 to 1.19 for ADPRT Val/Ala + Ala/Ala; adjusted OR 0.82, 95% CI 0.61 to 1.11 for XRCC1 Arg/Gln + Gln/Gln; and adjusted OR 0.70, 95% CI 0.45 to 1.10 for these two combined variant genotypes. Similarly, we did not find any significant associations of these two genotypes with BBD risk. These findings suggest that the ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms may not play a role in the etiology of breast cancer.

Adult↗
PubMed2006

[Gene transfer efficiencies and cell tropism of recombinant adeno-associated virus in the hippocampus of adult rat].

OBJECTIVE: To explore the gene transfer efficiencies and different cell tropism of recombinant adeno-associated virus 1 (rAAV1), rAAV 2, and rAAV 5 in the hippocampus of adult rats, and select more suitable gene vectors for central nervous system (CNS) gene therapy. METHODS: Eighteen SD male adult rat were divided into 3 groups randomly (n = 6), with every group being injected with the titre and volume matched rAAV1, rAAV2, and rAAV5 vectors. All these vectors contained enhanced green fluorescent protein (EGFP) sequences as a reporter gene. Animals were killed after 8 weeks. The coronal cryosections of brains were processed, and the EGFP gene expression was observed with fluorescence microscopy; the expression area and the number of EGFP positive cells were automatically measured using Image-Pro Plus 4.5 software. To identify their cell tropism in the CNS, the sections were counterstained with neuronal marker neuron-specific nuclear protein (NeuN) and the astrocyte marker glial fibrillary acidic protein (GFAP) and were examined with a confocal laser scanning microscope. RESULTS: Eight weeks after adeno-associated virus gene transfer, the expression profile of EGFP demonstrated significant difference. Most of the pyramidal cell layers of CA1 to CA3 area and granular cell of dent gyrus were strongly transduced by rAAV1; whereas rAAV2 primarily transduced the cells of multiform layer in hilar region of the dentate gyrus; only a few pyramidal cells were transduced by rAAV5. Moreover, rAAV1 showed significantly wider distribution throughout the hippocampus, and the quantity of EGFP positive cells and the EGFP positive area were significantly more than those of rAAV2 and rAAV5 (P < 0.01). The counterstaining for NeuN and GFAP showed that rAAV1 was able to transduce both neurons and glia cells, whereas rAAV2 and rAAV5 transduced the neurons only. CONCLUSION: rAAV1 is an excellent transgene vector with higher efficiency and broader cell tropism in the CNS.

Animals↗
PubMed2006

The association of polymorphisms of CDT1 and GMNN gene with the risk of breast cancer in Chinese women: a case-control analysis.

OBJECTIVE: To investigate the association of polymorphisms of CDT1 and GMNN gene, two important genes participating in DNA replication, with the risk of sporadic breast cancer. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis (PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a case-control study of 427 breast cancer cases and 477 cancer-free controls in a Chinese population. RESULTS: No significant association of the CDT1 838G/A and GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95% CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a significant association of CDT1 GA+AA genotypes with breast cancer risk among subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20-4.09). CONCLUSION: These findings suggest that the CDT1 838G/A and GMNN 387C/A polymorphisms may not play a major role in the etiology of breast cancer, but CDT1 variant may have a potential role only in genetically susceptible women.

Adult↗
PubMed2005

Joint effects of single nucleotide polymorphisms in P53BP1 and p53 on breast cancer risk in a Chinese population.

p53-binding protein 1 (P53BP1), a central transducer of DNA-damage signals to p53, is required for both intra-S-phase and G2-M checkpoints, suggesting that these two proteins may work together in the p53-mediated transcriptional activation and DNA damage-repair signaling pathways. Because the p53-binding region of 53BP1 maps to the C-terminal BRCT domains, which are homologous to those found in the breast cancer protein BRCA1, we hypothesized that genetic variation in P53BP1 and p53 may contribute to breast cancer predisposition. To test this hypothesis, we simultaneously genotyped single nucleotide polymorphisms of T-885G, Glu353Asp, and Gln1136Lys in P53BP1 and Arg72Pro in p53 in a case-control study of 404 breast cancer cases and 472 cancer-free controls. We found that the P53BP1 variant genotypes (alleles) of T-885G and Gln1136Lys were associated with a significantly increased risk of breast cancer among p53 Pro/Pro carriers (OR=2.36, 95% CI 1.16-4.83 for -885TG/GG; OR=2.24, 95% CI 1.15-4.37 for 1136Gln/Lys+Lys/Lys and OR=2.82, 95% CI 1.15-6.94 for >4 variant alleles of these 3 loci). In addition, the variant genotypes of above 3 loci of P53BP1 were significantly associated with elevated risk of progesterone receptor (PR) negative breast cancer, and the T-885G and Gln1136Lys with estrogen receptor (ER) negative breast cancer. Furthermore, we found a significant gene-gene interaction between P53BP1 Gln1136Lys and p53 Arg72Pro variants in relation to breast cancer, and the OR of interaction for the presence of both P53BP1 1136Gln/Lys+Lys/Lys and p53 72Arg/Pro+Pro/Pro genotypes was 1.93 (95% CI 1.06-3.52) (P=0.031 for interaction). These findings indicate that the SNPs in P53BP1 and p53 jointly contribute to breast cancer risk, particularly ER (-) or PR (-) breast cancer, and the p53 Arg72Pro polymorphism may serve as a risk modifier. Further functional studies are needed to confirm our findings.

Adult↗
PubMed2005

Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death.

Acid-sensing ion channels (ASICs) composed of ASIC1a subunit exhibit a high Ca(2+) permeability and play important roles in synaptic plasticity and acid-induced cell death. Here, we show that ischemia enhances ASIC currents through the phosphorylation at Ser478 and Ser479 of ASIC1a, leading to exacerbated ischemic cell death. The phosphorylation is catalyzed by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity, as a result of activation of NR2B-containing N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) during ischemia. Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by alanine (ASIC1a-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented ischemia-induced enhancement of ASIC currents, cytoplasmic Ca(2+) elevation, as well as neuronal death. Thus, NMDAR-CaMKII cascade is functionally coupled to ASICs and contributes to acidotoxicity during ischemia. Specific blockade of NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other pathological conditions involving excessive glutamate release and acidosis.

Acid Sensing Ion Channels↗
PubMed2005

Global kinetic model: a case study on the N-oxidation of alkylpyridines.

The homogeneous catalytic N-oxidation of two picolines and two lutidines by hydrogen peroxide has been studied calorimetrically using a heat flow and power compensation SIMULAR reaction calorimeter. The objective of this work was to extend a previously developed kinetic model [J. Sempere, R. Nomen, J.L. Rodriguez, M. Papadaki, Modelling of the reaction of 2-methylpyridine using hydrogen peroxide and a complex metal catalyst, Chem. Eng. Process. 37 (1998) 33-46] for 2-methylpyridine to more reactions in the same family. The kinetic model is in good agreement with our experimental data on beta-picoline. 3,5-Lutidine is in adequately good agreement with the model. However, the formation of two phases during the course of the reaction imposes the need for modifications to allow for mass transfer considerations. The N-oxidation of 2,6-lutidine is controlled by the addition or availability of hydrogen peroxide. A different reactor design is necessary for operation at the kinetic regime. High temperatures and catalyst concentrations enhance the selectivity towards N-oxidation of all alkylpyridines studied. The power evolution of all reactions has similar profiles thus indicating that similar kinetics are followed. The study of the N-oxidation of this family of compounds indicates that it is possible to design a process where hydrogen peroxide decomposition can be practically totally suppressed.

Calorimetry↗
PubMed2005

Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats.

The anterior cingulate cortex (ACC) is critically involved in processing the affective component of pain sensation. Visceral hypersensitivity is a characteristic of irritable bowel syndrome. Electrophysiological activity of the ACC with regard to visceral sensitization has not been characterized. Single ACC neuronal activities in response to colorectal distension (CRD) were recorded in control, sham-treated rats and viscerally hypersensitive (EA) rats (induced by chicken egg albumin injection, i.p). The ACC neurones of controls failed to respond to 10 or 30 mmHg CRD; only 22% were activated by 50 mmHg CRD. Among the latter, 16.4% exhibited an excitatory response to CRD and were labelled 'CRD-excited' neurones. In contrast, CRD (10, 30 and 50 mmHg) markedly increased ACC neuronal responses of EA rats (10%, 28% and 47%, respectively). CRD produced greater pressure-dependent increases in ACC spike firing rates in EA rats compared with controls. Splanchnicectomy combined with pelvic nerve section abolished ACC responses to CRD in EA rats. Spontaneous activity in CRD-excited ACC neurones was significantly higher in EA rats than in controls. CRD-excited ACC neurones in control and EA rats (7 of 16 (42%) and 8 of 20 (40%), respectively) were activated by transcutaneous electrical and thermal stimuli. However, ACC neuronal activity evoked by noxious cutaneous stimuli did not change significantly in EA rats. This study identifies CRD-responsive neurones in the ACC and establishes for the first time that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization, characterized by increased spontaneous activity of CRD-excited neurones, decreased CRD pressure threshold, and increased response magnitude. Enhanced ACC nociceptive transmission in viscerally hypersensitive rats is restricted to visceral afferent input.

Albumins↗
PubMed2005

Time-dependent four-component relativistic density-functional theory for excitation energies. II. The exchange-correlation kernel.

We extend our previous formulation of time-dependent four-component relativistic density-functional theory [J. Gao, W. Liu, B. Song, and C. Liu, J. Chem. Phys. 121, 6658 (2004)] by using a noncollinear form for the exchange-correlation kernel. The new formalism can deal with excited states involving moment (spin)-flipped configurations which are otherwise not accessible with ordinary exchange-correlation functionals. As a first application, the global potential-energy curves of 16 low-lying omega omega-coupled electronic states of the AuH molecule have been investigated. The derived spectroscopic parameters, including the adiabatic and vertical excitation energies, equilibrium bond lengths, harmonic and anharmonic vibrational constants, fundamental frequencies, and dissociation energies, are grossly in good agreement with those of ab initio multireference second-order perturbation theory and the available experimental data.

Journal Article↗
PubMed2005

Ryanodine receptor-mediated rapid increase in intracellular calcium induced by 7,8-benzo(a)pyrene quinone in human and murine leukocytes.

Benzo(a)pyrene (BaP) is an environmentally prevalent polycyclic aromatic hydrocarbon (PAH) known to produce immunotoxicity in murine and human lymphocytes. Previous studies by our lab have shown that certain BaP metabolites increase intracellular Ca(2+) in human and murine lymphocytes. The mechanism by which these BaP metabolites increase Ca(2+) may involve src kinase activation and mitochondrial oxidative stress. We have implicated a new pathway of Ca(2+) elevation in lymphocytes produced by a novel BaP metabolite, BaP-7,8-dione (7,8-BPQ). This ortho quinone is produced from BaP-7,8-dihydrodiol by aldoketoreductase 1C1 (AKR1C) isoforms in human cells. We have previously shown that 7,8-BPQ increases Ca(2+) levels in an in vitro rabbit skeletal muscle sarcoplasmic reticulum (SR) vesicle model via interaction with ryanodine receptors (RyR). In the present study, we found that 7,8-BPQ produced a RyR-dependent rapid increase in intracellular Ca(2+) in the Daudi human B cell line. However, other BP-diones including 1,6-, 3,6-, and 6,12-BPQs failed to produce a rapid increase in Ca(2+). Instead they produced a late increase in intracellular Ca(2+), presumably via a redox-cycling-dependent loss of Ca(2+) buffering capacity by mitochondria. Functional RyR were detected in Daudi using a (3)H-ryanodine binding assay. The studies were extended to normal human peripheral blood and murine spleen cells, where it was found that 7,8-BPQ rapidly elevated intracellular Ca(2+) in B cells and T cells in both species. The Ca(2+)-elevating effect of 7,8-BPQ was prevented by pretreatment with a high concentration of ryanodine (500 muM). Collectively, these results demonstrate a novel mechanism of Ca(2+) elevation by an environmentally relevant metabolite of BaP in murine and human lymphocytes.

Animals↗
PubMed2005

Cytochrome P450 1B1 is required for 7,12-dimethylbenz(a)-anthracene (DMBA) induced spleen cell immunotoxicity.

7,12-Dimethylbenz(a)anthracene (DMBA) is a potent carcinogen that induces immunosuppression of both humoral and cell-mediated immunity in mice and other species. Previous studies have shown that CYP1B1 is required for bone marrow toxicity produced by DMBA in mice. Therefore, the purpose of these studies was to determine whether CYP1B1 was required for spleen cell immunotoxicity. Female C57BL/6N wild-type (WT) and CYP1B1 knockout (-/-) mice were treated with 0, 17, 50, or 150 mg/kg (cumulative dose) DMBA in corn oil by oral gavage once a day for five days. Several immunotoxicological assays were used to assess the effects of DMBA on systemic immunity. These included the in vitro T-dependent antibody response to sheep red blood cells (SRBC) measured using a direct plaque forming cell (PFC) assay, T- and B-cell mitogenesis induced by Con A and LPS, and nonspecific cell-mediated immunity was evaluated using an NK cytotoxicity assay. In addition, lymphocyte subpopulations were measured by flow cytometry using specific cell surface markers. Following five days of DMBA treatment, the body weights and spleen cell surface markers of the WT and CYP1B1 (-/-) mice showed no significant changes. A decrease in NK activity was found at the 50 mg/kg DMBA dose in WT mice, but not in the CYP1B1 (-/-) mice. Interestingly, at the 150 mg/kg dose of DMBA, CYP1B1 null mice had decreased NK activity, whereas WT mice did not. The SRBC PFC response demonstrated that the IgM antibody response was suppressed by DMBA in WT mice in a dose-dependent manner (significant at 50 and 150 mg/kg). However, there were no changes in the SRBC PFC responses in any DMBA test group in the CYP1B1 (-/-) mice. Similarly, while DMBA suppressed B- and T-cell mitogenesis at the 50 and 150 mg/kg dose levels in C57BL/6N WT mice, no effect was seen in CYP1B1 (-/-) mice. Thus, CYP1B1 appears to be critical for the immunosuppression of DMBA in mice, suggesting a role for bioreactive metabolites in the spleen cell immunotoxicity produced by DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2005

Influence of secondary components on the synthesis of self-cross-linked N-isopropylacrylamide microgels.

This work presents systematic studies of cross-linker-free microgels formed by copolymerization of N-isopropylacrylamide (NIPAAm) and various secondary monomer components in water under standard reaction conditions. The sizes, solid densities, and volume phase transitions of these particles have been characterized through static and dynamic laser light-scattering experiments. We find that introducing a hydrophobic component, for example, styrene (St) or methyl methacrylate (MMA), leads to particles with smaller sizes and higher solid densities, while the volume phase transition shifts to lower temperatures. On the other hand, introducing a hydrophilic component such as acrylamide (AAm) or acrylic acid (AA) leads to larger particles with lower solid densities and a volume phase transition that shifts to higher temperatures and is broadened. The molar mass changes little in either case. Introducing a charged component such as sodium styrene sulfonate (NaSS) or poly(sodium styrene sulfonate) (PNaSS) leads to a sharp decrease in molar mass and particle size, and a very broad phase transition. These trends provide good guidance for synthesizing both self-cross-linked and cross-linked copolymerized microgels of different properties.

Journal Article↗
PubMed2005

Modified structural model for predicting particle size in the microemulsion and emulsion polymerization of styrene under microwave irradiation.

In this study, the microemulsion and emulsion polymerization of styrene at 70 degrees C in the presence of sodium dodecyl sulfate (SDS, surfactant) and potassium persulfate (KPS, initiator) was conducted under microwave radiation. Laser light scattering was used to characterize the resultant polystyrene latex particles formed at different polymerization stages. The influence of the initial emulsion composition, that is, the SDS, KPS, and styrene concentrations, on the final particle size led us to a simple modified structural model in which we considered the stabilization effects of both the surfactant and the ionic end groups generated from the initiator. This model extended the application of the previous Wu plot from microemulsion polymerization to emulsion polymerization. Using this model, we were not only able to control the particle size but were also able to predict the monomer concentration dependence of the number of the resultant latex particles and the effect of diluting the reaction mixture on the resultant particle size.

Journal Article↗
PubMed2005

The expression of intact and mutant human apoAI/CIII/AIV/AV gene cluster in transgenic mice.

The apoAI/CIII/AIV gene cluster is involved in lipid metabolism and has a complex pattern of gene expression modulated by a common regulatory element, the apoCIII enhancer. A new member of this cluster, apolipoprotein (apo) AV, has recently been discovered as a novel modifier in triglyceride metabolism. To determine the expression of all four apo genes in combination and, most importantly, whether the transcription of apoAV is coregulated by the apoCIII enhancer in the cluster, we generated an intact transgenic line carrying the 116-kb human apoAI/CIII/AIV/AV gene cluster and a mutant transgenic line in which the apoCIII enhancer was deleted from the 116-kb structure. We demonstrated that the apoCIII enhancer regulated hepatic and intestinal apoAI, apoCIII, and apoAIV expression; however, it did not direct the newly identified apoAV in the cluster. Furthermore, human apo genes displayed integrated position-independent expression and a closer approximation of copy number-dependent expression in the intact transgenic mice. Because apoCIII and apoAV play opposite roles in triglyceride homeostasis, we analyzed the lipid profiles in our transgenic mice to assess the effects of human apoAI gene cluster expression on lipid metabolism. The triglyceride level was elevated in intact transgenic mice but decreased in mutant ones compared with nontransgenic mice. In addition, the expression of human apoAI and apoAIV elevated high density lipoprotein cholesterol in transgenic mice fed an atherogenic diet. In conclusion, our studies with human apoAI/CIII/AIV/AV gene cluster transgenic models showed that the apoCIII enhancer regulated expression of apoAI, apo-CIII, and apoAIV but not apoAV in vivo and showed the influences of expression of the entire cluster on lipid metabolism.

Animals↗
PubMed2005

Energy metabolic profile of mice after chronic activation of central NPY Y1, Y2, or Y5 receptors.

OBJECTIVE: Neuropeptide Y (NPY), a 36-amino acid peptide with orexigenic properties, is expressed abundantly in the central nervous system and binds to several NPY receptor subtypes. This study examines the roles of the NPY Y1, Y2, and Y5 receptor(s) in energy homeostasis. RESEARCH METHODS AND PROCEDURES: We administered intracerebroventricular NPY (3 microg/d) or selective peptide agonists for the Y1, Y2, and Y5 receptor subtypes to C57Bl/6 mice for 6 days by mini-osmotic pumps to assess the role of each receptor subtype in NPY-induced obesity. Energy expenditure (EE) and respiratory quotient (RQ) were studied using indirect calorimetry. Adiposity was measured by DXA scanning and fat pad dissection. Insulin sensitivity was tested by whole-blood glucose measurement after an insulin challenge. RESULTS: Central administration of the selective Y1 agonist, Y5 agonist, or NPY for 6 days in mice significantly increased body weight, adiposity, and RQ, with significant hyperphagia in the Y5 agonist- and NPY-treated groups but not in the Y1 agonist-treated group. The NPY, Y1, or Y5 agonist-treated mice had little change in total EE during ad libitum and pair-feeding conditions. Conversely, selective activation of the Y2 receptor reduced feeding and resulted in a significant, but transient, weight loss. DISCUSSION: Central activation of both Y1 and Y5 receptors increases RQ and adiposity, whereas only Y5 receptor activation reduces energy expended per energy ingested. Selective activation of Y2 autoreceptors leads to hypophagia and transient weight loss, with little effect on total EE. Our study indicates that all three NPY receptor subtypes may play a role in regulating energy homeostasis in mice.

Absorptiometry, Photon↗
PubMed2005

Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients.

BACKGROUND: We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. METHODS: Between April 1999 and June 2002, 30 critically ill subjects requiring continuous renal replacement therapy and using 79 hemofilters were randomly assigned to receive regional citrate or systemic heparin anticoagulation. RESULTS: The median hemofilter survival time was 124.5 hours (95% CI 95.3 to 157.4) in the citrate group, which was significantly longer than the 38.3 hours (95% CI 24.8 to 61.9) in the heparin group (P < 0.001). Increasing illness severity score, male gender, and decreasing antithrombin-III levels were independent predictors of an increased relative hazard of hemofilter failure. After adjustment for illness severity, antithrombin-III levels increased significantly more over the period of study in the citrate as compared to the heparin group (P= 0.038). Moreover, after adjustment for antithrombin-III levels and illness severity score, the relative risk of hemorrhage with citrate anticoagulation was significantly lower than that with heparin (relative risk of 0.14; 95% CI 0.02 to 0.96, P= 0.05). CONCLUSION: Compared with systemic heparin anticoagulation, regional citrate anticoagulation significantly increases hemofilter survival time, and significantly decreases bleeding risk in critically ill patients suffering from acute renal failure and requiring continuous renal replacement therapy.

Acute Kidney Injury↗
PubMed2005

A high-throughput screen to identify inhibitors of amyloid beta-protein precursor processing.

Cerebral accumulation of the amyloid beta-peptide (Abeta) is believed to play a key role in the pathogenesis of Alzheimer's disease (AD). Because Abeta is produced from the proteolysis of amyloid beta-protein precursor (APP) by beta-and gamma-secretases, these enzymes are considered important drug targets for AD. The authors have developed a luciferase-based reporter system that can identify new molecules that inhibit APP processing in a high-throughput manner. Such molecules can help in understanding the biology of APP and APP processing and in developing new drug prototypes for AD. In this system, APP is fused on its C-terminus with Gal4-VP16, a chimeric yeast-viral transcription activator, and luciferase is under control of the yeast Gal4 promoter. Compounds that modulate the luciferase signal may affect the secretases directly, interact with modifiers of these proteases, or interact with APP directly. The authors successfully interfaced this assay with a high-throughput screen, testing approximately 60,000 compounds with diverse chemical structures. In principle, this sensitive, specific, and quantitative assay may be useful for identifying both inhibitors and stimulators of APP processing.

Amyloid Precursor Protein Secretases↗