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Biomedical subjects

R Wu

Publications and source records attributed to R Wu.

At least 55 records · Page 3Linked to original sources
PubMed2001

Arginine decarboxylase transgene expression and analysis of environmental stress tolerance in transgenic rice.

Arginine decarboxylase (ADC) cDNA from oat (Avena sativa L.) was introduced into rice (Oryza sativa L.) genome by an Agrobacterium-mediated transformation method. Expression of the ADC transgene under the control of an ABA-inducible promoter led to stress-induced upregulation of ADC activity and polyamine accumulation in transgenic rice plants. Second-generation (Rl) transgenic rice plants showed an increase in biomass under salinity-stress conditions, as compared to the non-transformed control plants.

Journal Article↗
PubMed2001

Phylogenetic placement of a novel tenuivirus from the grass Urochloa plantaginea.

Evidence is presented that a tenuivirus recovered from the grass Urochloa plantaginea is probably a novel tenuivirus species, to be called Urochloa hoja blanca virus (UHBV). It is related to both Echinochloa hoja blanca virus (EHBV) and Rice hoja blanca virus (RHBV), and these three form a group distinct from Maize stripe virus (MStV) and Rice stripe virus (RStV). Phylogenetic analysis of the sequence data for RNA-3 and RNA-4 of these viruses supports the hypothesis that EHBV and UHBV may have evolved from an ancestral form of RHBV, precipitated by the introduction of Echinochloa colona and Urochloa plantaginea to America.

Phylogeny↗
PubMed2001

Joint linkage and linkage disequilibrium mapping in natural populations.

A new strategy for studying the genome structure and organization of natural populations is proposed on the basis of a combined analysis of linkage and linkage disequilibrium using known polymorphic markers. This strategy exploits a random sample drawn from a panmictic natural population and the open-pollinated progeny of the sample. It is established on the principle of gene transmission from the parental to progeny generation during which the linkage between different markers is broken down due to meiotic recombination. The strategy has power to simultaneously capture the information about the linkage of the markers (as measured by recombination fraction) and the degree of their linkage disequilibrium created at a historic time. Simulation studies indicate that the statistical method implemented by the Fisher-scoring algorithm can provide accurate and precise estimates for the allele frequencies, recombination fractions, and linkage disequilibria between different markers. The strategy has great implications for constructing a dense linkage disequilibrium map that can facilitate the identification and positional cloning of the genes underlying both simple and complex traits.

Alleles↗
PubMed2001

A general polyploid model for analyzing gene segregation in outcrossing tetraploid species.

Polyploidy has played an important role in higher plant evolution and applied plant breeding. Polyploids are commonly categorized as allopolyploids resulting from the increase of chromosome number through hybridization and subsequent chromosome doubling or autopolyploids due to chromosome doubling of the same genome. Allopolyploids undergo bivalent pairing at meiosis because only homologous chromosomes pair. For autopolyploids, however, all homologous chromosomes can pair at the same time so that multivalents and, therefore, double reductions are formed. In this article, we use a maximum-likelihood method to develop a general polyploid model for estimating gene segregation patterns from molecular markers in a full-sib family derived from an arbitrary polyploid combining meiotic behaviors of both bivalent and multivalent pairings. Two meiotic parameters, one describing the preference of homologous chromosome pairing (expressed as the preferential pairing factor) typical of allopolyploids and the other specifying the degree of double reduction of autopolyploids, are estimated. The type of molecular markers used can be fully informative vs. partially informative or dominant vs. codominant. Simulation studies show that our polyploid model is well suited to estimate the preferential pairing factor and the frequency of double reduction at meiosis, which should help to characterize gene segregation in the progeny of autopolyploids. The implications of this model for linkage mapping, population genetic studies, and polyploid classification are discussed.

Crosses, Genetic↗
PubMed2001

A multivalent pairing model of linkage analysis in autotetraploids.

Polyploidy has been recognized as an important step in the evolutionary diversification of flowering plants and may have a significant impact on plant breeding. Statistical analyses for linkage mapping in polyploid species can be difficult due to considerable complexities in polysomic inheritance. In this article, we develop a novel statistical method for linkage analysis of polymorphic markers in a full-sib family of autotetraploids. This method is established on multivalent pairings of homologous chromosomes at meiosis and can provide a simultaneous maximum-likelihood estimation of the double reduction frequencies of and recombination fraction between two markers. The EM algorithm is implemented to provide a tractable way for estimating relative proportions of different modes of gamete formation that generate identical gamete genotypes due to multivalent pairings. Extensive simulation studies were performed to demonstrate the statistical properties of this method. The implications of the new method for understanding the genome structure and organization of polyploid species are discussed.

Algorithms↗
PubMed2001

Enhanced superoxide anion formation in vascular tissues from spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats.

OBJECTIVES: To investigate the basal and NADH-stimulated superoxide (.O2-) production and inactivation by Cu/Zn superoxide dismutase (SOD) in aorta from spontaneously hypertensive rats (SHR) and from desoxycorticosterone acetate (DOCA)-salt hypertensive (DOCA-HT) rats. METHODS: Tissue .O2- levels were estimated with the lucigenin-enhanced chemiluminescence method in aorta and cultured smooth muscle cells (SMCs) from SHR and in aorta from DOCA-HT rats treated for 4 weeks. RESULTS: The basal aortic .O2- generation was increased by 135 and 100%, and the NADH stimulated .O2- production was also increased 37 and 22% in SHR and in DOCA-HT rats compared to their normotensive controls, respectively. Although no difference existed in blood pressure as well as in basal and in NADH stimulated .O2- production between Wistar-Kyoto (WKY) rats and SHR rats at age of 6 weeks, O2- production and blood pressure increased concomitantly in SHR aged 9 and 12 weeks. Basal and NADH-stimulated .O2- production, in cultured SMCs, was also 80 and 64% higher, respectively, in SHR compared to WKY rats. The NADH oxidase activity was found to be increased in aorta from both SHR and DOCA-HT rats but SOD activity was reduced only in aorta from DOCA-HT rats. CONCLUSIONS: An enhanced .O2- formation resulting from an increased NADH oxidase activity was found in aorta from SHR and DOCA-HT rats. Cultured arterial SMCs from SHR also generated excessive .O2- formation under basal and stimulated conditions. The age-related increase in vascular .O2- formation in association with the rise in blood pressure in SHR suggests that the oxidative stress might contribute to the development of hypertension. NADH oxidase activity was greater in aorta of both hypertension models, but a decrease of Cu/Zn SOD activity could also contribute to the high level of aortic .O2- in DOCA-HT rats.

Aging↗
PubMed2001

A maximum likelihood-based method for mining major genes affecting a quantitative character.

In this article, we present a maximum likelihood-based analytical approach for detecting a major gene of large effect on a quantitative trait in a progeny population derived from a mating design. Our analysis is based on a mixed genetic model specifying both major gene and background polygenic inheritance. The likelihood of the data is formulated by combining the information about population behaviors of the major gene during hybridization and its phenotypic distribution densities. The EM algorithm is implemented to obtain maximum likelihood estimates for population and quantitative genetic parameters of the major locus. This approach is applied to detect an overdominant gene governing stem volume growth in a factorial mating design of aspen trees. It is suggested that further molecular genetic research toward mapping single genes affecting aspen growth and production based on the same experimental data has a high probability of success.

Algorithms↗
PubMed2001

Mice lacking the Nkx6.2 (Gtx) homeodomain transcription factor develop and reproduce normally.

The Nkx homeobox genes are expressed in a variety of developing tissues and have been implicated in controlling tissue patterning and cell differentiation. Expression of Nkx6.2 (Gtx) was previously observed in the embryonic neural tube, testis, and differentiating oligodendrocytes. To investigate the role of Nkx6.2 in the control of cell specification and differentiation, we generated mice with null mutations in Nkx6.2 using the standard gene targeting approach. Null mutant mice were viable and fertile without apparent histological and immunohistochemical changes in the central nervous systems and testis. The absence of detectable phenotypes suggests a redundant function of Nkx6.2 in mouse development.

Animals↗
PubMed2001

Microsatellite instability and the clinicopathological features of sporadic colorectal cancer.

BACKGROUND AND AIMS: In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice. METHODS: DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53. RESULTS: Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%. CONCLUSIONS: We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.

Adult↗
PubMed2001

Mechanism of dexamethasone-mediated interleukin-8 gene suppression in cultured airway epithelial cells.

The effects of dexamethasone, a glucocorticoid analog, on interleukin 8 (IL-8) gene expression were studied in cultures of primary human tracheobronchial epithelial cells and an immortalized human bronchial epithelial cell line, HBE1 cells. Dexamethasone inhibited IL-8 mRNA and protein expression in a concentration- and time-dependent manner. The inhibition did not occur at the transcriptional level since both nuclear run-on activity and IL-8 promoter-reporter gene expression assay revealed no significant effect. Instead, there was a change in IL-8 mRNA stability in dexamethasone-treated cultures. Under actinomycin D treatment, IL-8 mRNA was quite stable in dexamethasone-depleted cultures, while in dexamethasone-pretreated cultures, IL-8 message was rapidly degraded within the first hour, then leveled off. When dexamethasone and actinomycin D were added simultaneously to dexamethasone-depleted cultures, IL-8 mRNA remained rather stable. When cycloheximide was used to inhibit new protein synthesis, dexamethasone-dependent inhibition was not observed. These results suggest that a posttranscriptional mechanism, which requires dexamethasone-dependent new protein synthesis, is involved in the regulation of IL-8 mRNA by dexamethasone in airway epithelial cells.

Cells, Cultured↗
PubMed2001

Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression.

Excessive airway mucus is an important cause of morbidity and mortality in asthma, but the relationship between accumulation of mucus and goblet cell size, number, and function is incompletely understood. To address these questions, stored mucin in the epithelium and goblet cell size and number were measured morphometrically, and mucin gene expression was measured by polymerase chain reaction and immunohistochemistry in endobronchial biopsies from 13 subjects with mild and moderate asthma and from 12 healthy control subjects. Secreted mucin was measured in induced sputum. We found that stored mucin in the airway epithelium was three times higher than normal in the subjects with asthma (p < 0.005). Goblet cell size was similar in both groups, but goblet cell number was significantly higher in the subjects with asthma (93,043 +/- 15,824 versus 41,959 +/- 9,230/mm3, p < 0.05). In mild asthma (FEV1 > or = 80% pred, n = 7), the level of stored mucin was as high as in moderate asthma (FEV1 < 80% pred, n = 6), but the level of secreted mucin was significantly lower (28.4 +/- 6.3 versus 73.5 +/- 47.5 microg/ml, p < 0.05). Secreted mucin was inversely correlated with stored mucin for the whole asthma group (rs = -0.78, p = 0.007). MUC5AC was the predominant mucin gene expressed in healthy subjects and subjects with asthma, and MUC5AC protein was increased in the subjects with asthma. We conclude that even mild asthma is associated with goblet cell hyperplasia and increased stored mucin in the airway epithelium, whereas moderate asthma is associated with increased stored mucin and secreted mucin. These findings suggest that acute degranulation of hyperplastic goblet cells may represent a mechanism for asthma exacerbations in mild and moderate asthma and that chronic degranulation of goblet cells may contribute to chronic airway narrowing in moderate asthma.

Adult↗
PubMed2001

Activation of nuclear factor-kappa b transcriptional activity in airway epithelial cells by thioredoxin but not by N-acetyl-cysteine and glutathione.

Increasing evidence indicates that intracellular redox status modulates the activity of various transcriptional factors, including nuclear factor (NF)-kappa B and activator protein-1. Our laboratory has been interested in characterizing the role thioredoxin (TRX) plays in regulating cellular redox status in airway epithelium. TRX is a small, ubiquitous protein with two redox-active half-cysteine residues, -Cys-Gly-Pro-Cys, in its active center. Using primary passage-1 human tracheobronchial epithelial cell cultures and an immortalized human bronchial epithelial cell line, HBE1, we observed that tumor necrosis factor (TNF)-alpha enhanced NF-kappa B transcriptional activity. This observation was based on gel mobility shift assays and interleukin (IL)-8 promoter-reporter gene transfection studies. TNF-alpha activation coincided with translocation of NF-kappa B p65 from the cytoplasm to the nucleus. Pretreatment with N-acetyl-cysteine (NAC) (1 to 10 mM) or glutathione (1 to 10 mM) inhibited TNF-alpha-induced activation of NF-kappa B transcriptional activity and IL-8 promoter-mediated reporter gene expression. In contrast, elevated TRX protein levels in cells enhanced TNF-alpha-dependent NF-kappa B transcriptional activity and IL-8 promoter activity. This observation was independent of the manner in which TRX was elevated in cells (e.g., by cotransfection with a FLAG-TRX expression clone, or by direct exposure to commercially available human TRX protein). Localization of TRX protein by anti-TRX antibody indicated an accumulation of TRX protein in the nucleus after TNF-alpha treatment. The nuclear localization phenomenon was different from the major cytosolic accumulation of glutathione and NAC. This is the first known report demonstrating movement of TRX into the nucleus of airway epithelial cells after an inflammatory stress. These results suggest a compartment effect of thiol chemicals in the regulation of redox-dependent transcriptional activity.

Acetylcysteine↗
PubMed2001

Differential regulation of airway mucin gene expression and mucin secretion by extracellular nucleotide triphosphates.

The effects of extracellular nucleotide triphosphates on the stimulation of mucin production by airway epithelial cells were examined. The order of potency in stimulating mucin secretion in primary cultures of human tracheobronchial epithelial cells is: uridine 5'-triphosphate (UTP) approximately equal to adenosine 5'-triphosphate (ATP) approximately equal to ATP-gamma-S > uridine 5'-diphosphate approximately equal to adenosine 5'-diphosphate > alpha,beta-methylene ATP >> adenosine. However, only UTP can increase mucin gene (MUC5AC, MUC5B) expression; ATP and other analogues have no stimulatory effect. The stimulation of MUC5AC and MUC5B expression by UTP is time- and dose-dependent. A similar effect on the elevation of mucous cell population in mouse airway epithelium can be demonstrated in vivo by an intratracheal instillation of UTP-saline solution. The stimulatory effect of UTP or ATP on mucin secretion was inhibited by pertussis toxin, U73122, and Calphostin C, but not by PD98059, suggesting a G-protein/ phospholipase (PL) C/protein kinase (PK) C-dependent and mitogen-activated protein kinase (MAPK)-independent signaling pathway. However, the stimulatory effect of UTP on mucin gene expression was sensitive to pertussis toxin and PD98059, but not to Calphostin C and U73122, suggesting a G-protein/MAPK-dependent and PLC/PKC-independent signaling pathway. These findings are the first demonstration that UTP, a pyrimidine nucleotide triphosphate, can enhance both mucin secretion and mucin gene expression through different signaling pathways.

Adenosine Triphosphate↗
PubMed2001

Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5'-flanking region.

Human mucin (MUC) 5B gene expression in human airway epithelium was studied in both tissue sections and cultures of tracheobronchial epithelial (TBE) cells. In situ hybridization demonstrated that MUC5B message was expressed mainly in the mucous cells of submucosal glands of normal human airway tissues. Nevertheless, an elevated MUC5B message level could be seen in surface goblet cells from patients with airway diseases and inflammation. Regardless of the airway tissue sources, MUC5B message was regulated by all-trans-retinoic acid (RA) and culture conditions in both primary and passage-1 cultures of TBE cells. MUC5B message, to a lesser extent, was also found in the immortalized epithelial cell line HBE1, but not in BEAS-2B cells. To elucidate the molecular mechanism of MUC5B gene expression, a genomic clone was obtained and sequenced for the amino terminal and the 5'-flanking region of MUC5B gene. A luciferase reporter construct containing 4,169 base pairs of the 5'-flanking region of MUC5B gene demonstrated a cell type-specific basal promoter activity in transfection studies. Both RA and the air-liquid interface culture condition further enhanced this promoter activity. These results suggest that the 5'-flanking region of MUC5B gene contains cis-elements that are potentially involved in the regulation of MUC5B gene expression.

5' Flanking Region↗
PubMed2001

Gender-related differences in the characteristics of problem gamblers using a gambling helpline.

OBJECTIVE: The characteristics of male and female gamblers utilizing a gambling helpline were examined to identify gender-related differences. METHOD: The authors performed logistic regression analyses on data obtained in 1998-1999 from callers to a gambling helpline serving southern New England. RESULTS: Of the 562 phone calls used in the analyses, 349 (62.1%) were from male callers and 213 (37.9%) from female callers. Gender-related differences were observed in reported patterns of gambling, gambling-related problems, borrowing and indebtedness, legal problems, suicidality, and treatment for mental health and gambling problems. Male gamblers were more likely than female gamblers to report problems with strategic or "face-to-face" forms of gambling, e.g., blackjack or poker. Female gamblers were more likely to report problems with nonstrategic, less interpersonally interactive forms of gambling, e.g., slot machines or bingo. Female gamblers were more likely to report receiving nongambling-related mental health treatment. Male gamblers were more likely to report a drug problem or an arrest related to gambling. High rates of debt and psychiatric symptoms related to gambling, including anxiety and depression, were observed in both groups. CONCLUSIONS: Individuals with gambling disorders have gender-related differences in underlying motivations to gamble and in problems generated by excessive gambling. Different strategies may be necessary to maximize treatment efficacy for men and for women with gambling problems.

Adult↗
PubMed2001

Long-term changes in off-lesion endocochlear potential after induction of localized lesions in the lateral wall.

Localized lesions were produced in various turns of the guinea pig cochlea by means of a photochemical reaction between systemically administered rose bengal dye and green light illumination. The endocochlear potential (EP) was measured at various off-lesion sites, and a morphological examination was performed. In a previous study, this same investigation was done at 3 days, at which time all sites apical to the lesion showed significant EP depression, and damage to the stria vascularis at the lesion was ongoing. In the present 2-week study, the apical EP values were not different from the basal values, and all experimental values were essentially the same as the EP values found in control animals. Morphological examination revealed that the previously damaged structures were greatly repaired. Localized damage and early apical EP depression followed by damage repair and eventual EP recovery could account for the clinical course of certain cases of idiopathic sudden hearing loss involving low-tone deafness.

Animals↗
PubMed2001

Antiphospholipid antibody levels in intravenous immunoglobulin (IVIg) preparations.

The antiphospholipid syndrome (APS) is characterized by various clinical manifestations and by elevated levels of antiphospholipid antibodies. Passive induction of APS by infusion of these antibodies has been demonstrated in animal models. Intravenous immunoglobulin (IVIg) is one of the therapeutic options in APS. In this study, five commercially used preparations of IVIg were tested for the presence of elevated levels of cardiolipin, beta-glycoprotein-I, phosphatidylserine, antinuclear, and double-stranded DNA autoantibodies, as well as for lupus anticoagulant activity. The absence of abnormal elevated levels of any of these autoantibodies in five different IVIg preparations provides additional evidence for the safety of IVIg use in APS.

Antibodies, Anticardiolipin↗