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Biomedical subjects

P Wu

Publications and source records attributed to P Wu.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effects of long-term enalapril and losartan therapy of heart failure on cardiovascular aldosterone.

Plasma aldosterone escape is found during long-term ACE inhibitor therapy of chronic heart failure. Evidence for aldosterone production in cardiovascular tissues raised the question of whether aldosterone escape occurs or not in these tissues. Rats with infarction-induced chronic heart failure were treated with enalapril (20 mg/kg/d) and losartan (15 mg/kg/d) for 20 weeks. Untreated chronic heart failure and sham-operated rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high performance liquid chromatography, and RIA for aldosterone were performed. Chronic heart failure due to myocardial infarction was associated with tissue-specific activation of cardiovascular aldosterone synthesis. In the mesenteric artery, enalapril significantly inhibited aldosterone production compared to untreated, chronic heart failure rats, and losartan lowered aldosterone production to that of sham rats. In myocardium, enalapril failed to significantly inhibit aldosterone production, and losartan significantly inhibited aldosterone production compared to untreated, chronic heart failure rats. These results provide the first evidence that long-term ACE inhibition therapy induces aldosterone escape in myocardium but not in mesenteric artery of chronic heart failure. The angiotensin II subtype 1 receptor blocker losartan tranquilized aldosterone levels in the cardiovascular tissues of chronic heart failure rats.

Aldosterone↗
PubMed2002

An intelligent sales forecasting system through integration of artificial neural networks and fuzzy neural networks with fuzzy weight elimination.

Sales forecasting plays a very prominent role in business strategy. Numerous investigations addressing this problem have generally employed statistical methods, such as regression or autoregressive and moving average (ARMA). However, sales forecasting is very complicated owing to influence by internal and external environments. Recently, artificial neural networks (ANNs) have also been applied in sales forecasting since their promising performances in the areas of control and pattern recognition. However, further improvement is still necessary since unique circumstances, e.g. promotion, cause a sudden change in the sales pattern. Thus, this study utilizes a proposed fuzzy neural network (FNN), which is able to eliminate the unimportant weights, for the sake of learning fuzzy IF-THEN rules obtained from the marketing experts with respect to promotion. The result from FNN is further integrated with the time series data through an ANN. Both the simulated and real-world problem results show that FNN with weight elimination can have lower training error compared with the regular FNN. Besides, real-world problem results also indicate that the proposed estimation system outperforms the conventional statistical method and single ANN in accuracy.

Algorithms↗
PubMed2002

Transduction of human neural progenitor cells using recombinant adeno-associated viral vectors.

Human neural progenitor cells (hNPCs) represent an attractive source for cell therapy of neurological disorders. Genetic modification of hNPCs may allow a controlled release of therapeutic proteins, suppress immune rejection, or produce essential neurotransmitters. In search of an effective gene delivery vehicle, we evaluated the efficiency of a recombinant adeno-associated viral (rAAV) vector expressing enhanced green fluorescent protein (CAGegfp). Our study demonstrated that CAGegfp efficiently transduced both proliferating and differentiated hNPCs in vitro. EGFP expression was detected as early as 1 day after exposure to CAGegfp and was detectable for up to 4 months. Following transduction, the growth rate of hNPCs slowed down, but they were still able to differentiate into neurons and glia. Furthermore, CAGegfp-modified hNPCs survived, differentiated and expressed EGFP after transplanting into spinal cord of adult rats. Our results indicated that rAAV vectors might be a useful tool in hNPC-based cell and gene therapy for neurological disorders.

Adenoviridae↗
PubMed2001

Human phosphodiesterase 8A splice variants: cloning, gene organization, and tissue distribution.

We have cloned cDNAs representing five full-length human phosphodiesterase (PDE) 8A splice variants (PDE8As 1-5) from testis and T cells. PDE8A1 encodes a hydrophilic protein of 829 amino acids, containing an N-terminal REC domain, a PAS domain, and a C-terminal catalytic domain. PDE8A2 encodes a protein of 783 amino acids, identical to PDE8A1 but lacking the PAS domain. PDE8A3 encodes a shorter protein equivalent to the C-terminal 449 amino acids of PDE8A1, containing the catalytic but not the REC and PAS domains. PDE8A4 and PDE8A5, though different from each other at the nucleotide level, encode an identical protein equivalent to the C-terminal 582 amino acids of PDE8A1, including half of the PAS domain. The PDE8A gene is revealed to contain 23 exons, and its exon-intron boundaries have been defined. In addition, we have mapped a common transcription initiation site, and further determined the upstream 5'-flanking sequence of 1740 bp containing the putative promoter. Compared to PDE8A1, PDE8As 2-5 appear to be expressed in much lower abundance. Among various tissues and organs, PDE8A1 and PDE8A2 are expressed at various levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Hypoxia down-regulates endostatin production by human microvascular endothelial cells and pericytes.

Endostatin is a potent anti-angiogenic factor derived from the C-terminal region of collagen XVIII and is implicated in the regulation of physiological and pathological angiogenesis. In this study, reverse transcription-polymerase chain reaction analysis of poly(A+) RNA demonstrated the presence of mRNA for collagen XVIII in human endothelial cells (EC) and pericytes, the very constituents of microvessels wherein angiogenesis takes place. Enzyme immunoassay revealed that both cell types liberated endostatin into culture media and that the endostatin levels were decreased by hypoxia, the principal cause of angiogenesis. Northern and Western blot analyses revealed that while the collagen XVIII/endostatin mRNA levels were invariant between hypoxic and normoxic conditions, the collagen XVIII protein levels in EC and pericytes decreased by hypoxia. Further, exogenously administered intact endostatin was significantly decreased when it was incubated with hypoxic conditioned media of endothelial cells or pericytes, but not with normoxic media. The results suggest that the reduction of autocrine endostatin may take an active part in hypoxia-driven angiogenesis.

Angiogenesis Inhibitors↗
PubMed2001

Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is mediated by peroxisome proliferator-activated receptor alpha.

Pyruvate dehydrogenase kinase isoform 4 (PDK4) is upregulated by starvation in many tissues of the body during starvation. This causes inactivation of the pyruvate dehydrogenase complex which blocks pyruvate oxidation and conserves lactate and alanine for gluconeogenesis. Enhanced PDK4 expression may be caused by the increase in free fatty acids that occurs during starvation. Free fatty acids can activate peroxisome proliferator-activated receptor alpha (PPARalpha), and activation of PPARalpha can promote PDK4 expression. This model is supported by the findings reported here that WY-14,643, a synthetic PPARalpha activator, increases PDK4 expression in wild-type mice but not in PPARalpha-null mice. Starvation likewise increases the expression of PDK4 in tissues of wild-type mice but not in tissues of PPARalpha-null mice. These findings document the functional importance of PPARalpha for PDK4 expression during starvation and suggest an important role for elevated free fatty acids in the induction.

Animals↗
PubMed2001

pH and cation effects on the properties of parallel pyrimidine motif DNA triplexes.

The effects of cytosine protonation and various cations on the properties of parallel pyrimidine motif DNA triplexes were intensively investigated and characterized by several different techniques, such as circular dichroism (CD) conformation, ultraviolet (UV) melting, differential scanning calorimetry (DSC) thermal denaturation, and surface plasmon resonance (SPR) real-time dynamics. The comparative CD spectra of the triplex and the corresponding homoduplexes showed that the negative peak at approximately 218 nm would be the eigenpeak of the Hoogsteen paired strand, and moreover, the formation pathway of a triplex was significantly pH-dependent and fell into three groups: under acidic conditions, the triplex is formed by a one-step docking, under near physiological conditions, the Watson-Crick duplex is first structured and then accepts the Hoogsteen third strand into its major groove, and under basic conditions, the triplex is not formed. The pH-dependent thermodynamics of the global triplex, the Watson-Crick antiparallel duplex, and the Crick-Hoogsteen parallel duplex were comparatively discussed for the first time. These data revealed that the thermodynamic stabilities of the Watson-Crick-Hoogsteen triplex and the Crick-Hoogsteen duplex would be strongly dependent on cytosine protonation, but a low-pH environment somewhat destabilized the Watson-Crick duplex. The binding energy of triplex formation would be different from the unfolding energy of triplex melting under acidic conditions due to the disparity in the pathway between the formation and unfolding of a triplex. Real-time dynamic measurements showed that the association and dissociation rate constants of a duplex-to-triplex formation are (1.98 +/- 0.24) x 10(3) M(-1) s(-1) and (4.09 +/- 0.96) x 10(-4) s(-1) at 20 degrees C and pH 6.0, respectively. The formation energy of the duplex-to-triplex transition derived from SPR measurements was in agreement with the unfolding energy of the free Hoogsteen paired duplex derived from UV measurements. The calorimetric enthalpies of the triplex-to-duplex-to-single transition were 39.3 and 75.3 kcal/mol under near physiological conditions (pH 7.0), respectively, which were underestimated relative to the van't Hoff enthalpies. In addition, the effects of various cations, ionic strength, mixed-valent cations, and the position of the C(+)xG.C triplets on the thermodynamics of the triplexes were addressed under near physiological conditions. The interaction of metal ions with the triplexes clearly depended on the type and ionic strength of the cations, and the efficiency with which the cations stabilized the global triplex was in the order Mg(2+) > Mn(2+) > Ca(2+) > Ba(2+) >> Na(+). These observations would be useful for the design of triplex-forming oligonucleotides for antigene drugs and therapeutic purposes.

Calorimetry, Differential Scanning↗
PubMed2001

Temperature sensitive nop2 alleles defective in synthesis of 25S rRNA and large ribosomal subunits in Saccharomyces cerevisiae.

Using molecular genetic techniques, we have generated and characterized six temperature sensitive (ts) alleles of nop2. All failed to support growth at 37 degrees C and one was also formamide sensitive (fs) and failed to grow on media containing 3% formamide. Conditional lethality is not due to rapid turnover of mutant Nop2p proteins at 37 degrees C. Each allele contains between seven and 14 amino acid substitutions and one possesses a nonsense mutation near the C-terminus. Mapping experiments with one allele, nop2-4, revealed that a subset of the amino acid substitutions conferred the ts phenotype and that these mutations have an additive effect. All six mutants exhibited dramatic reductions in levels of 60S ribosome subunits under non-permissive conditions as well as some reduction at permissive temperature. Processing of 27S pre-rRNA to mature 25S rRNA was defective in all six mutants grown under non-permissive conditions. Levels of the 40S ribosomal subunit and 18S rRNA were not significantly affected. Amino acid substitutions in nop2 conditional alleles are discussed in the context of the hypothesis that Nop2p functions both as an RNA methyltransferase and a trans-acting factor in rRNA processing and large ribosomal subunit biogenesis.

Alleles↗
PubMed2001

Nucleolar protein Nop12p participates in synthesis of 25S rRNA in Saccharomyces cerevisiae.

A genetic screen for mutations synthetically lethal with temperature sensitive alleles of nop2 led to the identification of the nucleolar proteins Nop12p and Nop13p in Saccharomyces cerevisiae. NOP12 was identified by complementation of a synthetic lethal growth phenotype in strain YKW35, which contains a single nonsense mutation at codon 359 in an allele termed nop12-1. Database mining revealed that Nop12p was similar to a related protein, Nop13p. Nop12p and Nop13p are not essential for growth and each contains a single canonical RNA recognition motif (RRM). Both share sequence similarity with Nsr1p, a previously identified, non-essential, RRM-containing nucleolar protein. Likely orthologs of Nop12p were identified in Drosophila and Schizosaccharomyces pombe. Deletion of NOP12 resulted in a cold sensitive (cs) growth phenotype at 15 degrees C and slow growth at 20 and 25 degrees C. Growth of a nop12Delta strain at 15 and 20 degrees C resulted in impaired synthesis of 25S rRNA, but not 18S rRNA. A nop13 null strain did not produce an observable growth phenotype under the laboratory conditions examined. Epitope-tagged Nop12p, which complements the cs growth phenotype and restores normal 25S rRNA levels, was localized to the nucleolus by immunofluorescence microscopy. Epitope-tagged Nop13p was distributed primarily in the nucleolus, with a lesser portion localizing to the nucleoplasm. Thus, Nop12p is a novel nucleolar protein required for pre-25S rRNA processing and normal rates of cell growth at low temperatures.

Alleles↗
PubMed2001

Characterization of human, dog and rabbit corpus cavernosum type 5 phosphodiesterases.

Human, dog and rabbit corpus cavernosum type 5 phosphodiesterases (PDE5) were isolated and their characteristics were compared. The three enzymes showed Km values of 0.8, 2.1 and 2.3 uM, respectively. They exhibited similar pH-dependence with optimal pH being 7.5. They required Mg++ for activity and the activity was suppressed by high concentrations of Zn++ (0.1-1 mM). Sildenafil potently inhibited the three enzymes with IC50 values of 3.6, 1.7 and 3.0 nM, respectively. Dipyridamole and IBMX (3-isobutyl-1-methylxanthine) each also inhibited the three enzymes with similar, albeit lower, potencies (IC50 about 1.1 and 5.7 uM, respectively). However, zaprinast exhibited a significantly higher potency against the rabbit enzyme (IC50 53 nM) than against the human and dog PDE5s (IC5s 332 and 217 nM, respectively). Thus, the corpus cavernosum PDE5s are very similar among the various species with the only significant difference being their sensitivity to zaprinast. Human platelet PDE5 was also characterized by comparison with the corpus cavernosum enzyme. The platelet enzyme exhibited a Km, pH-, Mg++- and Zn++-dependence, and sensitivity to sildenafil and zaprinast very similar to those of the corpus cavernosum PDE5. However, compared with corpus cavernosum PDE5, the platelet enzyme exhibited higher sensitivity to dipyridamole and IBMX (IC50 0.46 and 1.8 uM, respectively). This study shows that despite similar kinetics and enzymatic properties, corpus cavernosum PDE5s from different species, and corpus cavernosum and platelet PDE5s, can have differential sensitivity to pharmacological inhibitors.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Glycoproteins H and L of Marek's disease virus form a hetero-oligomer essential for translocation and cell surface expression.

Glycoproteins H and L form a hetero-oligomeric complex (gH-L) which plays an important role in virus entry to host cells and cell-to-cell infection in herpesviruses. Interaction of gH and gL is considered to be critical for the biological function of these two glycoproteins. To investigate the interaction of MDV gH and gL, both gH and gL were expressed in in vitro cell culture systems using indirect immunofluorescence assay with gH and gL antibodies. The results suggested that co-expression of gH and gL in the same cells are required and necessary for both gH and gL subcellular translocation and cell surface expression. gL expressed in recombinant fowlpox virus (rFPV) infected chicken embryo fibroblasts (CEF) was consistently secreted into the culture medium. The primary peptide of gL binds with that of gH in the cytosol or ER lumen. By binding with gH, gL could anchor itself on the cell surface allowing for surface expression and viral spread to uninfected cells. The binding domain of gH was mapped to the amino acids 451-659 (SacI-HindIII) fragment and was essential for gH-L complex formation.

Animals↗
PubMed2001

Relationship between specific adverse life events and psychiatric disorders.

This study examines whether certain psychiatric disorders are associated more closely with adverse life events than other disorders are, and whether some adverse life events are associated with a specific group of disorders (e.g., depressive disorders), but not with other disorders (e.g., anxiety disorders). A probability sample of youth aged 9-17 at 4 sites is used (N = 1,285). Univariate and multivariate logistic regressions identify specific relationships between 25 adverse life events and 9 common child and adolescent psychiatric disorders, measured by the Diagnostic Interview Schedule for Children. Conduct Disorder, Oppositional Defiant Disorder, Major Depressive Disorder, and Dysthymia are significantly associated with many of the adverse life events examined, whereas Attention Deficit/Hyperactivity Disorder, Agoraphobia, and Social Phobia are related to very few. This study suggests that certain psychiatric disorders may be more closely associated with adverse life events than other psychiatric disorders are, and that some adverse life events seem to be related to specific types of disorders.

Adolescent↗
PubMed2001

Association between allergy and anxiety disorders in youth.

OBJECTIVE: Studies have documented associations between anxiety disorders and allergy in adults, but these associations have not been studied extensively in children. The objective of this study is to examine the associations between allergy and six anxiety disorders (AD) in youth. METHOD: This is a data analysis of two epidemiologic-services studies: (i) alternative service use patterns of youth with serious emotional disturbance (n = 936), and (ii) methods for the epidemiology of child and adolescent mental disorders (n = 1285). Child psychiatric diagnoses were measured by the diagnostic interview schedule for children. Allergy was assessed by the service utilization and risk factors interview. RESULTS: Among ADs, the strongest association found was between allergy and panic disorder (adjusted odds ratio 5.0; p < or = 0.001). Associations of allergy and the other ADs do not seem to be clinically significant. CONCLUSIONS: Findings suggest that in some patients panic disorder may be associated with hypersensitivity of immune system. Panic disorder should be considered in anxious children reporting allergy when no organic cause of allergy is found, and likewise allergy should considered in children with panic disorder.

Adolescent↗
PubMed2001

An outbreak of scabies in a teaching hospital: lessons learned.

OBJECTIVE: To investigate an outbreak of scabies in an inner-city teaching hospital, identify pathways of transmission, institute effective control measures to end the outbreak, and prevent future occurrences. DESIGN: Outbreak investigation, case-control study, and chart review. SETTING: Large tertiary acute-care hospital. RESULTS: A patient with unrecognized Norwegian (crusted) scabies was admitted to the acquired immunodeficiency syndrome (AIDS) service of a 940-bed acute-care hospital. Over 4 months, 773 healthcare workers (HCWs) and 204 patients were exposed to scabies. Of the exposed HCWs, 147 (19%) worked on the AIDS service. Risk factors for being infested with scabies among HCWs included working on the AIDS service (odds ratio [OR], 5.3; 95% confidence interval [CI95], 2.17-13.15) and being a nurse, physical therapist, or HCW with extensive physical contact with infected patients (OR, 4.5; CI95, 1.26-17.45). Aggressive infection control precautions beyond Centers for Disease Control and Prevention barrier and isolation recommendations were instituted, including the following: (1) early identification of infected patients; (2) prophylactic treatment with topical applications for all exposed HCWs; (3) use of two treatments 1 week apart for all cases of Norwegian scabies; (4) maintaining isolation for 8 days and barrier precautions for 24 hours after completing second treatment for a diagnosis of Norwegian scabies; and (5) oral ivermectin for treatment of patients who failed conventional therapy. CONCLUSIONS: HCWs with the most patient contact are at highest risk of acquiring scabies. Because HCWs who used traditionally accepted barriers while caring for patients with Norwegian scabies continued to develop scabies, we found additional measures were required in the acute-care hospital. HCWs with skin exposure to patients with scabies should receive prophylactic treatment. We recommend (1) using heightened barrier precautions for care of patients with scabies and (2) extending the isolation period for 8 days or 24 hours after the second treatment with a scabicide for those patients with Norwegian scabies. Oral ivermectin was well tolerated for treating patients and HCWs who failed conventional treatment. Finally, we developed a surveillance system that provides a "barometric measure" of the infection rate in the community. If scabies increases in the community, a tiered triage system is activated to protect against transmission among HCWs or hospital patients.

Adult↗