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Biomedical subjects

D Sun

Publications and source records attributed to D Sun.

At least 19 recordsLinked to original sources
PubMed2006

Linkage and association studies in African- and Caucasian-American populations demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence.

Our previous linkage study demonstrated that the 9q22-q23 chromosome region showed a 'suggestive' linkage to nicotine dependence (ND) in the Framingham Heart Study population. In this study, we provide further evidence for the linkage of this region to ND in an independent sample. Within this region, the gene encoding Src homology 2 domain-containing transforming protein C3 (SHC3) represents a plausible candidate for association with ND, assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerström Test for ND (FTND). We utilized 11 single-nucleotide polymorphisms within SHC3 to examine the association with ND in 602 nuclear families of either African-American (AA) or European-American (EA) origin. Individual SNP-based analysis indicated three SNPs for AAs and one for EAs were significantly associated with at least one ND measure. Haplotype analysis revealed that the haplotypes A-C-T-A-T-A of rs12519-rs3750399-rs4877042-rs2297313-rs1547696-rs1331188, with a frequency of 27.8 and 17.6%, and C-T-A-G-T of rs3750399-rs4877042-rs2297313-rs3818668-rs1547696, at a frequency of 44.7 and 30.6% in the AA and Combined samples, respectively, were significantly inversely associated with the ND measures. In the EA sample, another haplotype with a frequency of 10.6%, A-G-T-G of rs1331188-rs1556384-rs4534195-rs1411836, showed a significant inverse association with ND measures. These associations remained significant after Bonferroni correction. We further demonstrated the SHC3 contributed 40.1-59.2% (depending on the ND measures) of the linkage signals detected on chromosome 9. As further support, we found that nicotine administered through infusion increased the Shc3 mRNA level by 60% in the rat striatum, and decreased it by 22% in the nucleus accumbens (NA). At the protein level, Shc3 was decreased by 38.0% in the NA and showed no change in the striatum. Together, these findings strongly implicate SHC3 in the etiology of ND, which represents an important biological candidate for further investigation.

Adult↗
PubMed2006

Tumor-specific therapeutic effect induced by an oncolytic adenoviral vector containing heat shock protein 70 and prodrug activation genes.

We constructed a melanoma-specific oncolytic adenoviral vector Ad.MCDIRESE1.71Hsp3, in which the cytosine deaminase and adenoviral E1A genes linked by the IRES sequence were under the control of a mouse tyrosinase enhancer/promoter transcriptional element in the E1 region of the vector. We also inserted the human heat shock protein 70 (Hsp70) gene driven by the cytomegalovirus promoter into the E3 region of this vector. The RGD-4C peptide was inserted into the HI loop of the fiber knob domain of the Ad.MCDIRESE1.71Hsp3 vector to increase the transduction efficiency of this vector to tumor cells. The Ad.MCDIRESE1.71Hsp3 vector replicates specifically in melanoma cells, and it has a melanoma-specific cytotoxic effect in the presence of 5-fluorocytosine in vitro and in vivo. Moreover, the in vivo killing of tumor cells associated with the overexpression of Hsp70 generated by the intratumoral injection of the Ad.MCDIRESE1.71Hsp3 vector into established subcutaneous tumors can lead to the suppression of tumor growth and potent melanoma-specific systemic immune responses.

Adenoviridae↗
PubMed2006

Inhibition of Na+/H+ exchanger isoform 1 attenuates mitochondrial cytochrome C release in cortical neurons following in vitro ischemia.

Na+/H+ exchanger isoform 1 (NHE1) is a major acid extrusion mechanism following intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to disruption of Na+ homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Oxygen and glucose deprivation (OGD) for 3 hours followed by 21 hours of reoxygenation (REOX) led to 68 +/- 10% cell death. Inhibition of NHE1 with the potent inhibitor HOE 642 or genetic ablation of NHE1 reduced OGD-induced cell death by approximately 40% to 50% (p < 0.05). In NHE1 +/+ neurons, OGD/REOX triggered significant increases in Na+ and Ca(i)2+. Genetic ablation of NHE1 and HOE 642 treatment reduced the rise of Na(i)+ by approximately 40% to 50% and abolished the OGD/REOX-mediated Ca2+ accumulation. Moreover, mitochondrial cytochrome C release was significantly attenuated by inhibition of NHE1 activity. These results imply that NHE1 activity disrupts Na+ and Ca2+ homeostasis and contributes to ischemic neuronal damage.

Animals↗
PubMed2005

Differential gene expression in liver of inbred chickens and their hybrid offspring.

Differential display of mRNA was used to analyse the differences of gene expression in liver between chicken hybrids and their parents in a 4 x 4 diallel crosses in order to study the molecular basis of heterosis in chickens. The results indicated that patterns of gene expression in hybrids differ significantly from their parents. Four patterns of differential gene expression were revealed, which included: (i) bands only detected in the hybrid F1s (UNF1); (ii) bands only absent in the hybrid F1s (ABF1); (iii) bands only detected in the parental P1 or P2 lines (UNP1 and UNP2) and (iv) bands absent in the parental P1 or P2 lines (ABP1 and ABP2). In addition, correlations between patterns of gene expression and heterosis percentages of nine carcass traits of 8-week-old chickens were evaluated. Statistical results showed that negative correlations between heterosis percentages and the percentage of F1-specific bands (UNF1) were significant at P < 0.01 for breast muscle yield, leg muscle yield, wing weight, eviscerated weight and eviscerated weight with giblet of 8-week-old chickens, and at P < 0.05 for intermuscular fat width. Heterosis percentage was negatively correlated with ABP (bands present in the hybrid F1s and one parental line but absent in the other parental line, ABP1 and ABP2) for breast muscle yield, leg muscle yield, wing weight, eviscerated weight and eviscerated weight with giblet of 8-week-old chickens (P < 0.01). Bands detected only in the hybrid F1s but not in either of the parental lines (UNF1) and bands absent in parental P1 or P2 lines (which includes ABP1 and ABP2) may play important roles in chicken heterosis.

Animals↗
PubMed2005

[13C] phenylalanine breath test and hepatic phenylalanine metabolism enzymes in cirrhotic rats.

BACKGROUND: Stable isotope 13C-labelled phenylalanine breath test has been applied to enable the quantitative evaluation of hepatic functional reserve, but the mechanism underlying the changes in function has not been resolved. This study evaluated the correlation between expression of the mRNA of key enzymes mediating phenylalanine metabolism and the metabolism of L-[1-13C] phenylalanine (13C-phe) assessed by the excretion of 13C-CO2 in the breath of rats with, and without, chronic hepatic injury induced by administration of carbon tetrachloride (CCl4). MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats (n = 29) were given subcutaneous injections of CCl4 to induce chronic hepatic injury. L-[1-13C] phenylalanine breath tests (PheBT) were then applied to the rats to assess hepatic function. Expression of phenylalanine hydroxylase (PHH) and tyrosine transaminase (TYT) mRNA in liver was detected by real-time fluorescence quantification RT-PCR, using TaqMan as the probe. It was then determined whether the PheBT results correlated with PHH and/or TYT mRNA expression. In addition, immunohistochemical labelling was used to visualize PHH protein expression in the control and injured liver tissue. RESULTS: There were significant decreases in PheBT and PHH mRNA expression in the cirrhotic rats relative to the uninjured controls and these two measures of liver function were correlated. However, TYT mRNA expression was not changed by CCl4-induced liver injury. The immunohistochemical analysis revealed that PHH protein was expressed predominantly in the cytoplasm of liver cells. CONCLUSIONS: The results of the PheBT were consistent with the changes in PHH gene expression following liver injury. The present findings indicate that decreased expression of the rate-limiting enzyme PHH, but not of TYT, might underlie the functional deficits detected as decreased PheBT. The 13C excretion rate constant per mass liver (PheBT-k/LW) was the most sensitive index that could be used to evaluate the PHH mRNA expression in the liver.

Animals↗
PubMed2005

Electrohydrodynamic deposition of nanostructured lead zirconate titanate.

The deposition of a propanol-based lead zirconate titanate (PZT) sol using electrohydrodynamic atomization (EHDA) in the stable cone-jet mode was investigated. The droplets generated were deposited onto a copper substrate as a film, which was investigated using X-ray diffraction and scanning electron microscopy. The PZT film was shown to contain uniform nano-particles of PZT, which maintained their shape on sintering (650 degrees C, 1 hour) while forming the perovskite phase of PZT.

1-Propanol↗
PubMed2004

Pure motor mononeuropathy with distal conduction block: an unusual presentation of multifocal motor neuropathy with conduction blocks.

OBJECTIVE: To report an hitherto undescribed presentation of Motor Neuropathy with Multifocal Conduction Block (MMNCB). METHODS: Description of two patients presenting with complete paralysis of the 3 heads of the trapezius muscle (case one) and progressive weakness of finger extension (case 2). RESULTS: Nerve conduction studies (NCS) established that the corresponding nerves were distally inexcitable. In the affected muscles, no voluntary activity was elicited in both patients with spontaneous activity noted in patient 2. Systematic NCSs documented an asymptomatic, partial conduction block (CB) in a median nerve forearm segment in both patients. Neurophysiological follow-up after a dramatic response to intravenous immunoglobulins demonstrated recovery of the initially unobtainable motor responses. CONCLUSIONS: This indicates that a complete, distal CB of the motor fibers destined to the trapezius muscle in patient 1, and to the extensor indicis proprius in patient 2, had caused the heralding deficits. SIGNIFICANCE: These findings underscore the possibility of distal CB in this disorder and the need for extensive NCSs, including asymptomatic nerves, for an accurate diagnosis.

Adult↗
PubMed2004

An asthma-associated genetic variant of STAT6 predicts low burden of ascaris worm infestation.

Th-2 immune mechanisms are involved in the pathology of asthma and in the protective immune response to parasitic worms. Common upregulating genetic variants of Th-2 immune signalling are risk factors for asthma, and we tested whether they may confer a counteradvantage in protecting against parasitic worms. We examined the intensity of infection by the parasitic worm, Ascaris lumbricoides, by microsopic counting of ascaris eggs in the stool of 614 schoolchildren from an area of endemic ascaris infection in China. We investigated the relationship between the intensity of ascaris infection and common, asthma-associated genetic variants of Th-2 and Th-1 immune signalling. Ascaris egg counts per gram of stool (epg), mean 1068 epg, ranged from barely detectable (<240 epg) to heavy (approximately 9600 epg) in a skewed distribution. Logistic regression, after exploratory discriminant analysis, showed a major association between a common genetic variant of the 3'-UTR regulatory elements of the signal transducer and transactivating factor (STAT6) (P=0.0002) and egg counts, at the 77 th centile. Linear regression after log transformation of egg counts confirmed a highly significant association with this STAT6 variant (P=0.001). Thus, a common, asthma-associated, genetic variant of the pivotal transduction and transactivating factor for Th-2 immune signalling, STAT6, predicts increased resistance to ascaris worm infection. The evolution of enhanced resistance to parasitic worm infection, through human genetic variation in Th-2 immune signalling, may represent one origin for asthma.

3' Untranslated Regions↗
PubMed2004

Cytokine-induced enhancement of autoimmune inflammation in the brain and spinal cord: implications for multiple sclerosis.

UNLABELLED: Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are autoimmune inflammatory diseases in which cytokines are intimately involved. Here we test the hypothesis that injection of pro-inflammatory cytokines, tumour necrosis factor-alpha (TNFalpha) and interferon gamma (IFNgamma) into the brain of animals in the prodromal phase of EAE significantly enhances inflammation in the central nervous system (CNS). We were particularly interested to learn whether a local increase in cytokines influenced the pathology locally, or more extensively, within the CNS. EAE was induced in female adult Lewis rats. Eight days post-inoculation, TNFalpha or INFgamma was injected into one cerebral hemisphere. Days 11 and 13 post-inoculation (3 and 5 days after the injection of cytokine) inflammation was quantified by the number of perivascular cuffs and the degree of major histocompatibility complex (MHC) class II expression by microglia. Normal animals injected with cytokines, and EAE animals with saline injection served as controls. RESULTS: microglial activation was increased three- to fourfold in the brain and eightfold in the spinal cord (P </= 0.05); lymphocyte invasion was increased sixfold in the brain and three- to fourfold in the spinal cord (P </= 0.01) following injections of TNFalpha or INFgamma in EAE animals compared with controls. Significant axonal damage was observed in white matter associated with the perivascular cuffs. CONCLUSION: local changes in the release of pro-inflammatory cytokines within the brain in EAE results in the widespread enhancement of autoimmune inflammation within the brain and cord, and exacerbation of clinical symptoms.

Animals↗
PubMed2004

Removal of natural organic matter from water using a nano-structured photocatalyst coupled with filtration membrane.

A study of the characteristics of a novel photocatalyst indicated that it consisted of 17.3 nm nano size (average) TiO2 in the anatase phase and porous Fe2O3. SEM results revealed that nano size TiO2 was uniformly deposited onto the surface of Fe2O3 to form a bulk photocatalyst, as TiO2/Fe2O3. The porous TiO2/Fe2O3 catalyst had a BET surface area of 168 m2/g, which is three times higher than that of commercial TiO2. The experimental results indicated that the suspended TiO2/Fe2O3 photocatalyst in a photocatalytic oxidation (PCO) reactor was effective in removing TOC at 61.58% and color400 at 93.25% at 180 min illumination time, under 0.4 g/l catalyst loading and pH 7. Experimental results also revealed that pH at 7 and TiO2/Fe2O3 loading at 0.4 g/l was the optimum condition for removal of humic acids using a PCO reactor. Experimental results clearly indicated that the permeate flux rate of the ultrafiltration (UF) membrane was improved and the filtration membrane fouling phenomenon was reduced with the addition of TiO2/Fe2O3 photocatalysts to the UF membrane system. It was found that increasing the filtration time from 40 min to 185 min, the improvement to the permeate flux rate was from 57 to 83 L/hr x m2.

Catalysis↗
PubMed2003

Cutaneous stimulation improves function of a chronic patient with cerebellar damage.

The prognosis of cerebellar hemorrhage with brain stem compression is known to be poor, and patients who can usually survive are severely disabled with limited benefit from conventional rehabilitation. An innovative cutaneous stimulation was administered to a chronic patient (2 years after the incidence) who has severe ataxia, gait imbalance and limb spasticity caused by cerebellar hemorrhage. After 8 months of intervention, patient's function as evaluated by two functional measures has improved by 40%. In addition, the patient's ataxia and hypotonia have improved significantly in which he has regained the abilities to grasp objects, sit upright, control his equilibrium, and monitor an electric wheelchair. The present case study demonstrated a significant improvement of a chronic severely disabled patient who received the intervention 2 years after the accident, suggesting that the cutaneous stimulation may be a possible effective neurologic intervention.

Adolescent↗
PubMed2003

Increasing cell membrane potential and GABAergic activity inhibits malignant hepatocyte growth.

Increasing hepatocyte membrane potentials by augmenting GABAergic activity inhibits nonmalignant hepatocyte proliferative activity. The objectives of this study were to document 1) potential differences (PDs) of four malignant hepatocyte cell lines, 2) GABAA receptor mRNA expression in the same cell lines, and 3) effects of restoring malignant hepatocyte PDs to levels approximating those of resting, nonmalignant hepatocytes. Hepatocyte PDs were documented in nonmalignant and malignant (Chang, HepG2, HuH-7, and PLC/PRF/5) hepatocytes with a fluorescent voltage-sensitive dye and GABAA receptor expression by RT-PCR and Western blot analyses. Compared with nonmalignant human hepatocytes, all four malignant cell lines were significantly depolarized (P < 0.0001, respectively). Only PLC/PRF/5 cells had detectable GABAA-beta3 receptor mRNA expression and all cell lines were negative for GABAA-beta3 receptor protein by Western blot analysis. Stable transfection of Chang cells with GABAA-beta3 receptor cDNA resulted in significant increases in PD and decreases in proliferative activity as manifest by decreased [3H]thymidine and bromodeoxyurieine incorporation rates, 4-[3-(4-lodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate activity, a lower mitotic index, prolongation of cell-doubling times, and attenuated growth patterns compared with cells transfected with vector alone. Colony formation in soft agar and the number of abnormal mitoses were also significantly decreased in GABAA-beta3 receptor transfected cells. The results of this study indicate 1) relative to healthy hepatocytes, malignant hepatocytes are significantly depolarized, 2) GABAA-beta3 receptor expression is absent in malignant hepatocyte cell lines, and 3) increasing the PD of malignant hepatocytes is associated with less proliferative activity and a loss of malignant features.

Carcinoma, Hepatocellular↗
PubMed2003

Fouling and cleaning of microfiltration membrane in municipal wastewater reclamation.

This paper presents an investigation on fouling and cleaning of a tubular microfiltration membrane for municipal wastewater reclamation. A bi-level complex model, namely channel clogging and pore plugging, was introduced to elucidate the fouling mechanism. Based on 135 days of microfiltration of activated sludge, a preventive method for channel clogging was reasonably proposed and proven to be effective. Without channel clogging, the operation period was observed a five-fold increase on average, reaching 3-4 weeks. To remove pore plugging, a multi-step chemical cleaning was employed and further optimized in terms of temperature and alkaline concentration. Generally, the chemical cleaning could restore the membrane permeability to higher than 90%.

Biofilms↗
PubMed2002

Characterization of cockroach (Periplaneta americana) fat body phospholipase A(2) activity.

A phospholipase has been identified in the fat body of the American cockroach, Periplaneta americana, which removes fatty acid from the sn-2 acyl position of an artificial substrate. The enzyme has been characterized using a crude preparation obtained by low-speed centrifugation of the homogenized tissue. With 1-hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine as the substrate, the K(m) has been estimated to be 1.17 microM and the v(max) 113.5 pmol/min/mg protein. The phospholipase has a pH optimum close to 7 and shows maximal activity at 50 degrees C. Activity of the phospholipase has been determined in cytosolic and plasma membrane fractions. The specific activity of the latter fraction is approximately twice that of the cytosol. The enzyme in both fractions is Ca(2+)-independent. Arch.

Animals↗
PubMed2002

Stimulation of trehalose efflux from cockroach (Periplaneta americana) fat body by hypertrehalosemic hormone is dependent on protein kinase C and calmodulin.

Protein kinase C and calmodulin play key roles in cockroach fat body during activation of phosphorylase and trehalose efflux by HTH-II. The data support the view that an increase in cytosolic Ca2+ is prerequisite for enhanced activity of protein kinase C and calmodulin. Chelation of Ca2+ (i) with BAPTA blocks HTH-II-induced trehalose efflux from the fat body whereas thapsigargin, which raises [Ca2+]i to the same level as HTH-II, produces only a small, yet significant increase in trehalose efflux. Sphingosine, an inhibitor of protein kinase C, inhibits HTH-II-induced trehalose efflux in a concentration-dependent manner. Trehalose efflux is not activated by the protein kinase C activators OAG or PMA alone but in the presence of thapsigargin both agents increase trehalose efflux to a level comparable to that obtained with HTH-II. Thapsigargin has only a moderate activating effect on phosphorylase but in combination with OAG produces an activation indistinguishable from that provoked by HTH-II. Each of the structurally different calmodulin inhibitors, trifluoperazine, W-7, and calmidazolium, blocks completely the action of HTH-II on trehalose efflux, thus confirming the importance of calmodulin in HTH-II initiated trehalose efflux.

Animals↗
PubMed2002

Regulation of phospholipase A(2) activity in cockroach (Periplaneta americana) fat body by hypertrehalosemic hormone: evidence for the participation of protein kinase C.

Phospholipase A(2) (PLA(2)) associated with the membrane fraction of trophocytes from Periplaneta americana fat body increases by as much as 100% when the cells are incubated with hypertrehalosemic hormone (HTH-II). Activation with HTH-II is approximately halved by inclusion of the PKC inhibitor sphingosine in the incubation medium. Because activation of PLA(2) by HTH-II is blocked by the GDP analogue GDP-beta-S, and the unactivated enzyme is activated by the GTP analogue GTP-gamma-S it is likely that a G protein is involved in activation of the enzyme. Activation of PLA(2) was also achieved by treating the trophocytes with the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol in the presence of thapsigargin. This supports the view that protein kinase C is also involved in the activation process.

Journal Article↗
PubMed2002

Control of phospholipase A(2) activity in cockroach (Periplaneta americana) fat body trophocytes by hypertrehalosemic hormone: the role of calcium.

Recently, synthetic HTH-I and HTH-II have been shown to increase the formation of free fatty acids in cockroach (Periplaneta americana) fat body. In this study we show that HTH-II increases PLA(2) activity in dispersed trophocytes, thus implying that phospholipid is a potential source of the fatty acids. The increase in HTH-induced PLA(2) activity is triggered by an increase in [Ca(2+)](i) but extracellular Ca(2+) is also required for a maximal Ca(2+) signal: an effect that can be blocked by the introduction of BAPTA into the trophocytes. Treating trophocytes with ryanodine blocks the increase in PLA(2) activity that follows treatment of the cells with HTH-II. This indicates that the Ca(2+) release channels are distinct from those that respond to inositol trisphosphate. Thapsigargin, which releases Ca(2+) to the cytosol from an intracellular store, increases PLA(2) activity. The data show that the enzyme is translocated from the cytosol to the plasma membrane.

Acetophenones↗