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Biomedical subjects

D Su

Publications and source records attributed to D Su.

At least 19 recordsLinked to original sources
PubMed2006

The activation of lytic replication of Epstein-Barr virus by baculovirus-mediated gene transduction.

A baculoviral mammalian-cell vector was constructed to express Rta, a protein of Epstein-Barr virus (EBV) responsible for the transition from latent infection to lytic replication. EBV lytic replication and cell-growth inhibition was observed in infected D98/HR1 cells. The baculovirus caused little cytotoxicity in the non-targeted HeLa cells, compared to an adenovirus vector. It is concluded that recombinant baculovirus might have the potential as a vector for the therapy of EBV-related cancer.

Baculoviridae↗
PubMed2006

PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARalpha by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n=8; db/m, n=6) or a diet containing fenofibrate (db/db, n=8; db/m, n=7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P<0.001) and HbA1c levels (P<0.001), and was associated with decreased food intake (P<0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P<0.001) and reduced plasma insulin levels (P<0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P<0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P<0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARalpha, decreased type I collagen production. Taken together, the PPARalpha agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARalpha by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.

Albuminuria↗
PubMed2004

Contact lens microbial keratitis and prior topical steroid use: a disaster in the making?

INTRODUCTION: To review the best-corrected visual acuity, ulcer size, microbiological profile and morbidity of contact lens-related microbial keratitis with and without prior topical steroid use. MATERIALS AND METHODS: Retrospective case review of admitted cases of contact lens-related microbial keratitis in a tertiary hospital. Data pertaining to demographics, pre-admission treatment with or without topical steroids, ulcer size, duration of admission, Gram stain and culture results as well as the final best-corrected visual acuity were recorded. Patients are classified into 3 groups: Group 1 received no treatment prior to presentation, Group 2 received topical antibiotics only from their general practitioners and Group 3 prescribed both topical antibiotics and steroids. RESULTS: Forty-six cases were enrolled in the study, 41.3% had prior topical steroids (all dexamethasone) in combination with antibiotics. None of them had topical steroids alone. Large ulcers were associated with steroid use, odds ratio = 7.74 [95% confidence interval (CI), 1.18-50.56] and positivity of Gram stains odds ratio = 7.74 [95% CI, 1.18-50.56] whereas loss of more than 2 Snellen lines was associated with Pseudomonas aeruginosa infection, odds ratios of 21.70 [95% CI,2.09-225.03] and presence of central ulcer, 13.51 [95% CI, 2.33-78.3]. Prior topical steroid use was associated with longer duration of symptoms prior to admission but not duration of stay or surgical intervention. CONCLUSION: Patients with prior topical combined antibiotics-steroids present slightly later and with larger ulcers. However, the duration of stay, final visual acuity, treatment failure and complication rates were not statistically different from the non-treated group. This might be due to 1) early presentation and therefore early treatment of contact lens-related microbial keratitis and 2) the short duration of use of combined antibiotic-steroid eye drops.

Administration, Topical↗
PubMed2001

Generation of three selenium-containing catalytic antibodies with high catalytic efficiency using a novel hapten design method.

A novel strategy for design of haptens that were used to produce catalytic antibodies was developed and three monoclonal antibodies, 3G5, 2F3, and 5C9, were generated using this strategy. These monoclonal antibodies were converted into selenium-containing abzymes by chemically modifying the hydroxyl group of serines followed by sodium hydrogen selenide displacement. These selenium-containing abzymes exhibited remarkable glutathione peroxidase activity, which surpasses the activity of some native glutathione peroxidases. The activities of the selenium-containing abzymes Se-3G5, Se-2F3, and Se-5C9 which catalyzed reduction of hydroperoxides by glutathione were 2.23, 4.20, and 3.79 times that of rabbit liver glutathione peroxidase, respectively. Detailed steady-state kinetics study on Se-2F3 was carried out and the value of k(cat)/K(m) (H(2)O(2)) was found to be 2.11 x 10(7) M(-1) min(-1) which was supposed to be one of the highest among the known catalytic antibodies. The data of association constants and glutathione peroxidase activities of these catalytic antibodies and the steady-state kinetics of Se-2F3 showed that the method might be a remarkably efficient one for generating catalytic antibodies with glutathione peroxidase activity.

Amino Acid Sequence↗
PubMed2001

Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis.

The thymus and parathyroid glands in mice develop from a thymus/parathyroid primordium that forms from the endoderm of the third pharyngeal pouch. We investigated the molecular mechanisms that promote this unique process in which two distinct organs form from a single primordium, using mice mutant for Hoxa3 and Pax1. Thymic ectopia in Hoxa3(+/-)Pax1(-/-) compound mutants is due to delayed separation of the thymus/parathyroid primordium from the pharynx. The primordium is hypoplastic at its formation, and has increased levels of apoptosis. The developing third pouch in Hoxa3(+/-)Pax1(-/-) compound mutants initiates normal expression of the parathyroid-specific Gcm2 and thymus-specific Foxn1 genes. However, Gcm2 expression is reduced at E11.5 in Pax1(-/-) single mutants, and further reduced or absent in Hoxa3(+/-)Pax1(-/-) compound mutants. Subsequent to organ-specific differentiation from the shared primordium, both the parathyroids and thymus developed defects. Parathyroids in compound mutants were smaller at their formation, and absent at later stages. Parathyroids were also reduced in Pax1(-/-) mutants, revealing a new function for Pax1 in parathyroid organogenesis. Thymic hypoplasia at later fetal stages in compound mutants was associated with increased death and decreased proliferation of thymic epithelial cells. Our results suggest that a Hoxa3-Pax1 genetic pathway is required for both epithelial cell growth and differentiation throughout thymus and parathyroid organogenesis.

Animals↗
PubMed2001

Kinetics study of a selenium-containing ScFv catalytic antibody that mimics glutathione peroxidase.

The steady-state kinetics study and some enzymatic characterization of a selenium-containing scFv catalytic antibody (Se-scFv2F3) were carried out. A novel reaction formula of this abzyme-catalyzed reaction was proposed and a rate equation was obtained according to the formula. The constants in the equation were compared with Dalziel's parameters and the exact meanings of these constants were analyzed. The obtained kinetics parameters from the kinetics study of Se-scFv2F3 were analyzed and compared with those of native glutathione peroxidase.

Antibodies, Catalytic↗
PubMed2001

Kinetics study of a selenium-containing ScFv catalytic antibody that mimics glutathione peroxidase.

The steady state kinetic study and some enzymic characterization of a selenium-containing scFv catalytic antibody (Se-scFv2F3) was carried out. A novel reaction formula of this abzyme-catalyzed reaction was proposed and a rate equation was gotten according to the formula. The constants in the equation were compared with Dalziel's parameters and the exact meanings of these constants were analyzed. The gotten kinetics parameters from the kinetics study of Se-scFv2F3 were analyzed and compared with that of native glutathione peroxidase.

Antibodies, Catalytic↗
PubMed2001

Gamma -secretase inhibitors repress thymocyte development.

A major therapeutic target in the search for a cure to the devastating Alzheimer's disease is gamma-secretase. This activity resides in a multiprotein enzyme complex responsible for the generation of Abeta42 peptides, precipitates of which are thought to cause the disease. Gamma-secretase is also a critical component of the Notch signal transduction pathway; Notch signals regulate development and differentiation of adult self-renewing cells. This has led to the hypothesis that therapeutic inhibition of gamma-secretase may interfere with Notch-related processes in adults, most alarmingly in hematopoiesis. Here, we show that application of gamma-secretase inhibitors to fetal thymus organ cultures interferes with T cell development in a manner consistent with loss or reduction of Notch1 function. Progression from an immature CD4-/CD8- state to an intermediate CD4+/CD8+ double-positive state was repressed. Furthermore, treatment beginning later at the double-positive stage specifically inhibited CD8+ single-positive maturation but did not affect CD4+ single-positive cells. These results demonstrate that pharmacological gamma-secretase inhibition recapitulates Notch1 loss in a vertebrate tissue and present a system in which rapid evaluation of gamma-secretase-targeted pharmaceuticals for their ability to inhibit Notch activity can be performed in a relevant context.

Amyloid Precursor Protein Secretases↗
PubMed2001

A novel glutathione peroxidase mimic with antioxidant activity.

Many diseases are associated with the overproduction of hydroperoxides that inflict cell damage. A novel cyclodextrin derivative, 6A,6B-diseleninic acid-6A',6B'-selenium bridged beta-cyclodextrin (6-diSeCD), was synthesized to be a functional mimic of glutathione peroxidase (GPX) that normally removes these hydroperoxides. The mimic had high catalytic GPX activity of 13.5 U/micromol, which is 13.6-fold higher than ebselen (PZ51), and was chemically and biologically stable in vitro. Antioxidant activity was studied by ferrous sulfate/ascorbate-induced mitochondria damage model system. These data show that the mimic has great antioxidant activity. Such mimics may result in better clinical therapies for diseases mediated by hydroperoxides.

Animals↗
PubMed2000

First direct measurement of the parity-violating coupling of the Z0 to the s quark

We present the first direct measurement of A(s), the parity-violating coupling of the Z0 boson to the strange quark, using approximately 550 000 e(+)e(-)-->Z0-->hadrons events recorded by the SLC Large Detector with a polarized e(-) beam. We tagged Z0-->s&smacr; events by the absence of B or D hadrons and the presence in each hemisphere of a high momentum K+/- or K(0)(s). Fitting the polar angle distributions of the strangeness-signed thrust axis gave A(s) = 0.895+/-0.066(stat)+/-0.062(syst). The analyzing power and uu+d&dmacr; background were constrained using the data, greatly reducing any model dependence.

Journal Article↗
PubMed2000

Precise measurement of the b-quark fragmentation function in Z0 boson decays

We have developed a new technique for inclusive reconstruction of the energy of B hadrons. The excellent efficiency and resolution of this technique allow us to make the most precise determination of the b-quark fragmentation function, using e(+)e(-)-->Z0 decays recorded in the SLAC Large Detector experiment. We compared our measurement with the predictions of a number of fragmentation models. We excluded several of these models and measured the average scaled energy of weakly decaying B hadrons to be = 0.714+/-0. 005(stat)+/-0.007(syst)+/-0.002 (model dependence).

Journal Article↗
PubMed2000

CD40 ligand-induced apoptosis is Fas-independent in human multiple myeloma cells.

We and others previously demonstrated that human multiple myeloma (MM) cells express CD40 and have an active CD40-growth regulatory pathway. This study characterizes the growth outcome of soluble (gp39) or membrane-bound recombinant human CD40-ligand (rCD40L) and its relationship with Fas-dependent apoptosis. Contrary to the moderate growth-stimulatory effect of the CD40-MAb G28.5, gp39 inhibited 3H-thymidine uptake of the plasma dyscrasia lines ARH-77, U266, and HS-Sultan in a dose-dependent fashion by up to 82%. By comparison, RPMI 8226 cells were resistant to CD40L-growth modulation, which may be attributable to a single base substitution (TCA-->TTA, serine-->leucine) at the 3rd cysteine-rich extramembrane region of CD40. Gp39 similarly reduced myeloma clonogenic colony (MCC) formation in patient primary bone marrow cultures by 50% (40-76%; n=6). Studies using transfectant L cells that constitutively expressed CD40L showed that membrane-bound CD40L inhibited the growth of ARH-77, U266, and HS-Sultan cells (66%, 63%, and 32%, respectively), whereas untransfected L cells did not. Growth inhibition by gp39 or CD40L+ L cells was neutralized by coincubation with the CD40L antibodies 5c8 or LL48. CD40L-treatment increased apoptotic activity of MM cells, as defined by oligonucleosomal DNA fragmentation and an increased binding to annexin V (16-28%). All three untreated CD40-responsive MM lines expressed the Fas/Apo-1/CD95 antigen (65-92% CD95+). However, only ARH-77 cells responded to the growth inhibitory effect of the CD95-agonistic antibody CH-11. CD95 expression was not affected significantly by gp39 treatment, and growth inhibition by CH-11 was additive to gp39 (from 42% to 64% decrease in 3H-thmidine uptake). Conversely, the CD95 antagonist antibody ZB4 reversed the Fas-dependent growth inhibitory process but did not significantly alter gp39-mediated growth outcome. Gp39 treatment lowered the expression of TNFR-associated factors TRAF4 and TRAF6 by 38% and 32%, respectively, whereas detectable levels of TRAF1,2,3, and 5 levels remained unchanged. Our observations indicate that the CD40L-binding inhibits human MM cell growth and increases its apoptotic activity. This growth inhibitory effect corresponds to lower levels of cytoplasmic TRAF signaling elements, and appears independent of the Fas-signaling pathway. CD40 receptor mutation may lead to unresponsiveness to CD40 growth modulation in multiple myeloma cells.

Apoptosis↗
PubMed1999

NBPA: a cerebral ischaemic protective agent.

1. NBPA is a derivative of 3-n-butylpathalide isolated from Apium granolens Linn. 2. At concentrations ranging from 6 x 10(-6) to 10(-6) mol/L, NBPA inhibited the L-type calcium current in guinea-pig myocardial cells and cultured human neuroblastoma cells. 3. At 10(-6) mol/L, NBPA markedly inhibited calcium-dependent and -independent release of glutamate from synaptosomes. 4. The [31P] nuclear magnetic resonance spectrum has shown that pretreatment with NBPA at 15 mg/kg, i.p., improved energy metabolism. 5. In situ hybridization has shown that 10 and 20 mg/kg, i.p., NBPA prior to cerebral artery occlusion can accelerate the expression of heat shock protein 70 mRNA and inhibit c-fos mRNA expression. 6. It has been shown that NBPA decreases the nitric oxide content and bc nitric oxide synthase (NOS) activity in the global cerebral ischaemia-reperfusion model in rats. In addition, it has been shown that NBPA significantly inhibits the expression of inducible NOS protein.

Animals↗
PubMed1999

Hemoglobin infusion augments the tumor necrosis factor response to bacterial endotoxin (lipopolysaccharide) in mice.

OBJECTIVE: To determine whether cell-free hemoglobin augments the inflammatory cascade, as detected by production of tumor necrosis factor (TNF) elicited by bacterial endotoxin (lipopolysaccharide [LPS]). DESIGN: In vivo and ex vivo study, using a mouse model of sepsis. SETTING: Animal research facility SUBJECTS: Female Swiss Webster mice. INTERVENTIONS: For the in vivo experiments, an LD50 dose (500 microg) of Escherichia coli LPS was injected intraperitoneally into mice. Cell-free crosslinked hemoglobin (60 mg/mouse) or saline was administered intravenously 10 hrs before or coincident with LPS. For the ex vivo experiments, hemoglobin (60 mg/mouse) or saline was administered intravenously to mice, and, 10 hrs later, hepatic Kupffer cells, peripheral blood mononuclear cells, or peritoneal macrophages were isolated. MEASUREMENTS AND MAIN RESULTS: Intravenous infusion of hemoglobin either 10 hrs before or coincident with intraperitoneal LPS resulted in a peak of plasma TNF that was greater than in control mice administered LPS only. Cultured Kupffer cells, isolated from mice that had received hemoglobin in vivo 10 hrs before cell collection, produced more TNF in response to LPS in vitro than cells from normal mice. A trend toward greater TNF production in vitro by peripheral blood mononuclear cells obtained from hemoglobin-treated mice also was observed. Enhanced sensitivity to LPS was not observed with cultured peritoneal macrophages from mice that had received hemoglobin. CONCLUSIONS: Intravenous hemoglobin increased the sensitivity of hepatic macrophages to subsequent stimulation by LPS. This effect may contribute to the increased mortality that we have observed in animals that have received both LPS and hemoglobin.

Animals↗
PubMed1999

Prevention of baculovirus-induced apoptosis of BTI-Tn-5B1-4 (Hi5) cells by the p35 gene of Trichoplusia ni multicapsid nucleopolyhedrovirus.

A typical apoptosis of BTI-Tn-5B1-4 (Hi5) cells induced by Heliothis armigera single capsid nucleopolyhedrovirus (HaSNPV) infection was completely suppressed by coinfection with Trichoplusia ni multicapsid nucleopolyhedrovirus polyhedron-negative recombinant (TnMNPV-SVI- G) (OCC-) at a low multiplicity of infection (6.5 x 10(-2)). To determine whether TnMNPV p35 alone was sufficient to inhibit the apoptosis, two recombinant plasmids containing the early promoter of p35, or the very late promoter of TnMNPV polh were constructed to study p35 function by transient expression assay. It was shown that expression of p35 alone could partially prevent HaSNPV-induced apoptosis but did not facilitate HaSNPV replication in Hi5 cells. The data suggests that both P35 of TnMNPV and other unknown gene products are required for the suppression of apoptosis and facilitation of HaSNPV replication in Hi5 cells.

Animals↗
PubMed1998

Limulus antilipopolysaccharide factor prevents mortality late in the course of endotoxemia.

Limulus antilipopolysaccharide factor (LALF) can neutralize bacterial endotoxin, but its ability to prevent mortality following prolonged endotoxemia is unknown. Mice were challenged with an LD50 dose of intraperitoneal E. coli lipopolysaccharide (LPS) and then received LALF at various times after administration of LPS. Survival at 72 h was significantly improved by the administration of LALF at 4, 10, and even 24 h after LPS (73%, 78%, and 65% survival, respectively, vs. 15% survival in controls). Following intravenous administration of LALF at either 10 or 24 h after LPS, plasma levels of biologically active LPS abruptly fell (> 1000-fold lower than pre-LALF levels). Plasma LALF concentrations fell much more gradually in LPS-treated mice (t1/2 = 120 min) than in control mice (t1/2 = 2.5 min). In conclusion, LALF markedly decreased plasma concentrations of biologically active LPS and protected mice from lethality even when LALF was not administered until long after the onset of continuous endotoxemia.

Animals↗