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Biomedical subjects

Y Feng

Publications and source records attributed to Y Feng.

At least 73 records · Page 4Linked to original sources
PubMed2001

5'-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder.

Recently the molecular genetic basis of attention-deficit hyperactivity disorder (ADHD) has been the focus of a number of studies with the majority of these investigating the role of dopamine system genes. A great deal of attention has been focused on the possible involvement of the dopamine D4 receptor gene (DRD4) following a report of an association of ADHD with the allele containing seven copies of the 48-bp repeat in the third exon. In this paper we extended the search for the molecular explanation for the observed association by testing three polymorphisms in the region 5' to the dopamine receptor D4 gene transcription start site for linkage to ADHD. We specifically targeted polymorphisms in the region 5' to the start site of transcription as DNA variants in this region could alter the transcription level of the gene and hence the phenotype. We did not observe significant evidence for biased transmission of any of the alleles at these three polymorphisms to ADHD probands using the transmission disequilibrium test. We conclude that these three polymorphisms are not related to the ADHD phenotype.

5' Untranslated Regions↗
PubMed2001

X-irradiation of the contusion site improves locomotor and histological outcomes in spinal cord-injured rats.

We have determined whether X-irradiation of the injury site can oppose tissue loss and improve recovery of locomotor function following contusion injury of the spinal cord. Contusion injury was produced in rats at the level of T10 with a weight drop device. Localized X-irradiation (20 Gy) of the injury site was performed at 20 min and 1, 2, 4, 7, and 17 days postinjury. Locomotor recovery was then determined with the 21-point Basso, Beattie, and Bresnahan (BBB) scale. X-irradiation enhanced recovery of locomotor function during a subsequent 6-week observation period when administered 20 min and 1 or 2 days following contusion injury (final BBB score approximately 7-8). X-irradiation at 4-17 days postinjury did not significantly affect final locomotor scores compared with unirradiated rats (final BBB score approximately 2), in marked contrast to previous studies where X-irradiation applied only at 17-18 days benefitted transection injury. The extent of recovery was directly related to measurements of sparing of spinal cord tissue at the contusion center. Because the treatment time window occurred earlier in contusion than reported for transection injury, the results suggest that contusion injury rapidly initiates underlying radiation-sensitive processes that occur only following a delay of several weeks after transection injury. Further optimization of X-ray treatment may lead to a useful therapeutic modality for use in spinal cord contusion injury.

Animals↗
PubMed2001

The novel function of a short region K253xRxxxD259 conserved in the exonuclease domain of hyperthermostable DNA polymerase I from Pyrococcus horikoshii.

The DNA polymerase gene of the hyperthermophile Pyrococcus horikoshii was successfully overexpressed after removing an intein. The importance of an amino acid sequence around a highly conserved Asp was studied by site-directed mutagenesis. The results indicated that Lys253, Arg255, and Asp259 form a novel functional motif, K253xRxxxD259 (outside known motifs Exo I, II, and III), that is important not only for exonuclease activity but also for polymerizing activity, confirming functional interdependence between the polymerase and exonuclease domains. The short loop region, K253G254R255, probably contributes to binding to DNA substrates. Moreover, the negative charge and the side-chain length of D259 might play a supporting role in coordinating the conserved Mg2+ to the correct position at the active center in the exonuclease domain.

Amino Acid Sequence↗
PubMed2001

Inhibition of the mitogen activated protein kinase, p38 alpha, prevents proinflammatory cytokine induction by human adherent mononuclear leukocytes in response to lipid loading.

Macrophage infiltration, inflammatory processes and oxidatively modified low density lipoprotein (LDL) are known contributing factors in the formation of the atherosclerotic plaque. To determine whether a direct link might exist between these factors, we examined the effect of oxidized LDL upon proinflammatory cytokine production in adherent human peripheral blood mononuclear leukocytes. Oxidized LDL, as well as a combination of cholesterol and 25-hydroxycholesterol, induced tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1 beta) mRNA as measured by quantitative real time PCR, by a maximum of two- to fourfold following a 24-h incubation. Analysis of cell culture supernatants revealed a concomitant stimulation of TNFalpha and IL-1 beta secreted protein as determined by ELISA. Treatment of human peripheral blood mononuclear leukocytes with oxidized LDL or the combination of cholesterol and 25-hydroxycholesterol caused activation of p38 alpha as determined by the ability of immunoprecipitated p38 to phosphorylate an ATF-2 fusion protein, a surrogate substrate of p38 alpha. VK-19911 (Pyridine, 4-[4-(4-fluorophenyl)-1-(4-piperidinyl)-1H-imidazol-5-yl]-dihydrochloride), a specific inhibitor of p38 alpha, prevented the induction of TNFalpha and IL-1 beta by oxidized LDL in a dose-dependent manner. Activated p38 alpha is known to be involved in the stabilization of cyclooxygenase-2 mRNA in response to stimuli such as lipopolysaccharide; however, in the setting of oxidized LDL-induced p38 alpha activation, COX-2 mRNA levels were not affected. Taken together, the data imply a potential role for p38 alpha activation in lipid-associated inflammatory processes.

Activating Transcription Factor 2↗
PubMed2001

Distribution of proSAAS-derived peptides in rat neuroendocrine tissues.

Using a technique to identify substrates of the peptide processing enzyme carboxypeptidase E (CPE), several novel peptides were detected in the brain and pituitary of Cpe(fat)/Cpe(fat) mice and found to be derived from a single precursor, termed proSAAS. In order to gain further information regarding the potential physiological roles of these peptides, we have examined the distribution of two proSAAS-derived peptides, ARPVKEPRSLSAASAPLAETSTPLRL (SAAS) and LENSSPQAPARRLLPP (LEN), in rat neuroendocrine tissues using immunohistochemistry. Both peptides are detected throughout the brain, with the highest concentrations of SAAS peptide in the hypothalamus. In the hippocampus, both peptides are co-localized with prohormone convertase 1 in the dentate gyrus and CA1-3 region. In cerebellum, SAAS peptide is co-localized with prohormone convertase 1 in Purkinje and granular cells, whereas LEN is much more abundant in the Purkinje cells relative to the granular cells. Similarly, SAAS and prohormone convertase 1 are co-localized in the dorsal horn of the spinal cord, while LEN is mainly restricted to fibers of the white matter. In the pituitary, SAAS, LEN, and prohormone convertase 1 are detected in all three lobes. In the pancreas, SAAS, LEN, and prohormone convertase 1 are only detected in the islets, although the peptides are enriched in the peripheral cells (alpha and/or delta) while prohormone convertase 1 is only expressed in the inner cells (beta). Both SAAS and LEN are present in the adrenal medulla along with prohormone convertase 1. Taken together, these data are consistent with the proposed role for proSAAS as an endogenous inhibitor of prohormone convertase 1 in many, but not all cell types. However, the broader localization of the peptides allows for the possibility that they perform additional functions.

Adrenal Glands↗
PubMed2001

Effect of pH on the rheological and structural properties of gels of water-washed chicken-breast muscle at physiological ionic strength.

Adjustment of pH from 6.4 to neutrality improved gelling ability and water-holding capacity of twice water-washed, minced chicken-breast muscle significantly at physiological ionic strength, at which the majority of the myofibrillar proteins, including myosin, are not soluble. A strain value of 2.2 was obtained at neutral pH. Myofibrils were the main components of the gel network at both pH 6.4 and 7.0; however, the myofibrillar distribution varied with the pH value. At pH 6.4, myofibrils formed a network of localized aggregates leaving large voids between, whereas at neutral pH, an evenly distributed network of myofibrils was formed. In addition, at neutral pH, a network of fine strands was found within the network of myofibrils. The network was much less developed at pH 6.4. The thin and thick filaments within each myofibrillar structure were disorganized at both pH values. The intramyofibrillar spaces were larger at neutral pH than at pH 6.4. It was proposed that adjustment of pH to neutrality increased electrostatic repulsion leading to a more even distribution of the myofibrillar proteins, a key factor responsible for the improved gel strength and water-holding capacity.

Animals↗
PubMed2001

Structure-based combinatorial library design: discovery of non-peptidic inhibitors of caspases 3 and 8.

Structure-based design of a combinatorial array was carried out in order to identify non-peptidic thiomethylketone inhibitors of caspases 3 and 8. Five compounds from the designed array were active against caspase 3, and two were active against caspase 8. A 2.5-A resolution co-crystal structure of caspase 3 and a thiomethylketone array member is reported. The structure-based design strategy has proved useful for identifying caspase inhibitors.

Caspase 3↗
PubMed2001

Protein-protein interactions, cytoskeletal regulation and neuronal migration.

Neuronal migration, like the migration of many cell types, requires an extensive rearrangement of cell shape, mediated by changes in the cytoskeleton. The genetic analysis of human brain malformations has identified several biochemical players in this process, including doublecortin (DCX) and LIS1, mutations of which cause a profound migratory disturbance known as lissencephaly ('smooth brain') in humans. Studies in mice have identified additional molecules such as Cdk5, P35, Reelin, Disabled and members of the LDL superfamily of receptors. Understanding the cell biology of these molecules has been a challenge, and it is not known whether they function in related biochemical pathways or in very distinct processes. The last year has seen rapid advances in the biochemical analysis of several such molecules. This analysis has revealed roles for some of these molecules in cytoskeletal regulation and has shown an unexpected conservation of the genetic pathways that regulate neuronal migration in humans and nuclear movement in simple eukaryotic organisms.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Intracellular inhibition of the replication of hepatitis B virus by hammerhead ribozymes.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is frequently associated with cirrhosis and hepatocellular carcinoma, and so has become a major worldwide health problem. Hammerhead ribozymes have recently gained some attention as potential tools to inhibit viral infection, for which there are no general effective therapies available. METHODS: A hammerhead ribozyme, RzC, was designed to target the sequence encoding the tail region of the HBV core protein. The activities of the ribozyme were analyzed in vitro and in human hepatoma (HepG2) cells. RESULTS: In vitro, RzC cleaves HBV-RNA at its target site up to 30%, while the disabled ribozyme, dRzC, which has a one-base mutation in the catalytic site, did not cleave the target RNA at all. When the ribozymes were cotransfected into HepG2 cells with the HBV genome-containing plasmid, p3.6II, the inhibition of HBV replication by RzC was greater than that by dRzC, indicating that the active catalytic domain of the hammerhead ribozyme could increase the extent of antisense-mediated inhibition. In addition, there was a gradient of effectiveness in which the greater the amount of released ribozyme, the greater the reduction in HBV progeny DNA. CONCLUSIONS: These results suggest the possibility of hammerhead ribozyme-mediated gene therapy for the treatment of HBV infections.

Antiviral Agents↗
PubMed2001

Distinct molecular mechanisms lead to diminished myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase in qk(v) dysmyelination.

The genetic lesion of quakingviable (qk(v)) causes diminished expression of the QKI RNA-binding protein in myelin producing cells. Consequently, several structural myelin proteins are severely reduced. Among these affected proteins, the reduction of the myelin basic protein (MBP) results from post-transcriptional abnormalities of the MBP mRNA, presumably due to the lack of interactions with QKI. However, whether this is the common mechanism for reduced expression of other myelin proteins in qk(v) dysmyelination remains unclear. Here we report that distinct molecular mechanisms underlie the reduction of MBP and the 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in qk(v) dysmyelination. MBP transcripts bind QKI strongly and are markedly reduced in the qk(v)/qk(v) oligodendrocytes in which QKI is almost completely lost. In contrast, CNP transcripts bind QKI weakly and are only slightly affected by the lack of QKI. None the less, CNP proteins are severely reduced in the qk(v)/qk(v) brain. Since CNP transcripts are predominantly associated with translating polyribosomes, diminished CNP expression in qk(v) dysmyelination is unlikely to be due to translational failures, but more likely results from accelerated protein degradation.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed2001

Complex organization of promoter and enhancer elements regulate the tissue- and developmental stage-specific expression of the Drosophila melanogaster Gld gene.

The Drosophila melanogaster Gld gene has multiple and diverse developmental and physiological functions. We report herein that interactions among proximal promoter elements and a cluster of intronically located enhancers and silencers specify the complex regulation of Gld that underlies its diverse functions. Gld expression in nonreproductive tissues is largely determined by proximal promoter elements with the exception of the embryonic labium where Gld is activated by an enhancer within the first intron. A nuclear protein, GPAL, has been identified that binds the Gpal elements in the proximal promoter region. Regulation of Gld in the reproductive organs is particularly complex, involving interactions among the Gpal proximal promoter elements, a unique TATA box, three distinct enhancer types, and one or more silencer elements. The three somatic reproductive organ enhancers each activate expression in male and female pairs of reproductive organs. One of these pairs, the male ejaculatory duct and female oviduct, are known to be developmentally homologous. We report evidence that the other two pairs of organs are developmentally homologous as well. A comprehensive model to explain the full developmental regulation of Gld and its evolution is presented.

Animals↗
PubMed2001

Oral administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) yields PhIP-DNA adducts but not tumors in male Syrian hamsters congenic at the N-acetyltransferase 2 (NAT2) locus.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine carcinogen present in well-done meat. PhIP must undergo host-mediated bioactivation to exert its mutagenic and carcinogenic effects. Following N-hydroxylation, N-acetyltransferases catalyze the O-acetylation (activation) of N-hydroxy-PhIP to an electrophile causing DNA damage. A well-defined genetic polymorphism in N-acetyltransferase 2 (NAT2) activity exists in humans and the Syrian hamster. Since some human epidemiological studies suggest an association between acetylator genotype and cancer susceptibility in individuals who consume well done meats, this study was designed to investigate the specific role of acetylator genotype in PhIP-induced tumors using a Syrian hamster model congenic at the NAT2 locus. Following oral administration of PhIP to male rapid and slow acetylator Syrian hamsters, DNA adducts were identified in each tissue examined with levels in the relative order: pancreas > heart and urinary bladder > prostate, small intestine and transverse colon > ascending colon, liver, cecum, descending colon, and rectum. However, no tumors were observed in male rapid and slow acetylator congenic hamsters administered 11 oral doses of PhIP (75 mg/kg) and maintained on a high fat diet for one year.

Acetylation↗
PubMed2001

Diurnal variation of corneal and corneal epithelial thickness measured using optical coherence tomography.

PURPOSE: To determine the feasibility of optical coherence tomography (OCT) measurement of overnight corneal swelling and de-swelling and, specifically, to examine overnight changes in the corneal epithelium and recovery during the day. METHODS: Ten healthy volunteers were recruited. Corneal OCT imaging was performed at 10:00 PM (baseline), 8:30 AM, and every 2 hours thereafter until 4:30 PM. Either the right or left eye was taped shut (using a gauze pad and surgical tape) until the 8:30 AM session of the next day. Measurements were made along a 1-mm strip centered on the visual axis. RESULTS: At baseline, there were no differences in corneal or epithelial thickness between control and experimental eyes (all p > 0.05). Immediately after patch removal, corneal and epithelial thicknesses of patched eyes were higher than the baseline (all p < 0.05). In patched eyes, the cornea and epithelium swelled 5.5% and 8.1% overnight, respectively (p > 0.05). Two hours later, the epithelial thickness of the experimental eyes recovered to baseline level (p > 0.05), but corneal thickness did not reach to baseline level until 4 hours after patch removal. For control eyes, there were no differences compared with baseline (all p > 0.05). CONCLUSION: Both cornea and corneal epithelium experience proportionately similar amounts of overnight swelling. Recovery of overnight swelling may be slower for the cornea than for the epithelium. OCT provides valuable information about anterior segment morphometry.

Adult↗
PubMed2001

Coinfection of enteric Helicobacter spp. and Campylobacter spp. in cats.

During a 6-year period, 64 of 227 commercially reared cats had microaerobic bacteria isolated from their feces. All the isolates were initially identified as Campylobacter-like organisms based on biochemical and phenotypic characteristics. DNA extractions from 51 of these isolates were subjected to PCR using primers specific for Helicobacter spp. and Campylobacter spp. Of the isolates, 92% (47 of 51 isolates) were positive for Campylobacter spp., 41% (21 of 51 isolates) were positive for Helicobacter spp., 33% (17 of 51 isolates) were positive for both genera, 59% (30 of 51 isolates) were positive only for Campylobacter spp., and 8% (4 of 51) were positive only for Helicobacter spp. Sixteen of the 47 Campylobacter-positive cultures were positive for more than one Campylobacter spp. Based on a species-specific PCR assay, 83% of the isolates were identified as Campylobacter helveticus, 47% of the isolates were identified as Campylobacter upsaliensis, and 6% of the isolates were classified as Campylobacter jejuni. The 1.2-kb PCR products of the 16S rRNA genes of 19 Helicobacter species isolates were subjected to restriction fragment length polymorphism (RFLP) analysis. Of the five different RFLP patterns obtained, two clustered with Helicobacter ("Flexispira") taxon 8, one clustered with Helicobacter bilis, one clustered with Helicobacter canis, and the remaining pattern was closely related to a novel Helicobacter sp. strain isolated from a woodchuck. The sequence data for the 16S rRNA genes of 10 Helicobacter spp. validated the RFLP-based identification of these isolates. This study demonstrated that biochemical and phenotypic characteristics of microaerobic organisms in cat feces were insufficient to characterize mixed Helicobacter and Campylobacter infections. Molecular structure-based diagnostics using genus- and species-specific PCR, RFLP analysis, and 16S rRNA sequence analysis enabled the identification of multiple microaerobic species in individual animals. The clinical relevance of enteric Helicobacter and Campylobacter coinfection in cats will require further studies.

Animals↗
PubMed2001

Differential effects of overexpression of two forms of ephrin-A5 on neonatal rat cardiomyocytes.

Eph receptors constitute the largest family of receptor tyrosine kinases. Multiple transcripts of ephrin-A5, the cognate ligand of the EphA3 receptor, were found in neonatal rat cardiomyocytes. Two cDNA clones encoding the full-length ephrin-A5 (ephrin-A5 alpha) and a 27-amino acid deletion form (ephrin-A5 beta) were isolated. To examine the role of ephrin-A5 in cardiomyocytes, the cDNAs were inserted into adenoviral vectors, termed Ad.ephrin-A5 alpha and Ad.ephrin-A5 beta, respectively, and overexpressed in cardiomyocytes. The effect of ephrin-A5 on cardiomyocyte gene expression was investigated using a cDNA expression array and Western blot analysis. The results showed that both ephrin-A5 alpha and ephrin-A5 beta downregulated cyclin D2, cyclin-dependent kinase-4 proteins, and their cognate receptor EphA3, which were associated with reduced bromodeoxyuridine incorporation in cardiomyocytes. Whereas ephrin-A5 alpha and ephrin-A5 beta also induced differential gene expression, only ephrin-A5 beta significantly upregulated the transcription of brain natriuretic peptide and downregulated ras-related protein RAB2, protein kinase C inhibitor protein-1, clusterin, and insulin-like growth factor-binding protein. The results suggest that the two forms of ephrin-A5 share similar function while differ in regulating different sets of genes in cardiomyocytes.

Adenoviridae↗
PubMed2001

Cholangiohepatitis and inflammatory bowel disease induced by a novel urease-negative Helicobacter species in A/J and Tac:ICR:HascidfRF mice.

Helicobacter bilis and H. hepaticus, both urease-positive intestinal helicobacters of mice, have been shown experimentally to induce proliferative typhlocolitis in scid mice. We recently isolated a urease-negative Helicobacter sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studies in scid mice. To determine the pathogenic potential of H. sp. in immunocompromised and immunocompetent mice, 5-week old male A/J or Tac:Icr:Ha(ICR)-scidfRF mice were inoculated by intraperitoneal (IP) injection with approximately 3 x 10(7) colony-forming units (CFU) of H. sp. Mice were necropsied at various time points postinoculation (PI). Sham-inoculated mice had no clinical, gross, or histopathological lesions. In contrast, scid mice inoculated IP with H. sp. had severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks postinoculation (PI), with severe proliferative typhlocolitis, phlebothrombosis, and hepatitis. A/J mice had no clinical signs, but had mild to moderate proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24 weeks PI. A/J mice infected with H. sp. developed robust immune responses of a predominant Th1 type. This report demonstrates that infection with a urease-negative helicobacter can cause inflammatory bowel disease (IBD) and hepatitis in scid and immunocompetent A/J mice. These results provide a new model of IBD and cholangio-hepatitis associated with a specific urease-negative, novel H. species.

Animals↗
PubMed2001

Inhibition of hepatitis B virus by hammerhead ribozyme targeted to the poly(A) signal sequence in cultured cells.

The deviant poly(A) signal of hepatitis B virus (HBV) not only controls the formation of the 3' end of all the viral RNA, but is also crucial for HBV replication. Hence, a cis-releasing hammerhead ribozyme (RzA) targeted to the poly(A) signal region of HBV subtype adr was investigated for its antiviral effects. In vitro, RzA cleaved HBV RNA at its target site up to 70%, while the disabled ribozyme (dRzA), which had a one-base mutation in the catalytic site, did not cleave the target RNA at all. When the ribozymes were cotransfected into HepG2 cells with the HBV genome-containing plasmid p3.6II, the wild-type ribozyme RzA could effectively decrease HBV RNA levels and inhibit HBV replication, whereas its disabled form, dRzA, had much weaker effects, indicating that the active catalytic domain of the hammerhead ribozyme could markedly increase the extent of antisense-mediated inhibition. In addition, there was a gradient of effectiveness: the higher the amount of released ribozyme, the more the reduction in target HBV RNA in cells as well as progeny DNA reduction. These results suggest the possibility of the hammerhead ribozyme RzA to be used for the gene therapy of HBV infection.

Antiviral Agents↗