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Biomedical subjects

D Wu

Publications and source records attributed to D Wu.

At least 217 records · Page 12Linked to original sources
PubMed1999

Dietary conjugated linoleic acid influences the immune response of young and old C57BL/6NCrlBR mice.

Aging is associated with a decline in the immune response in mammals. Conjugated linoleic acid (CLA) has been suggested to have immunoenhancing properties. We examined the influence of dietary CLA on the immune response of young and old mice. Forty young (4 mo) and 40 old (22 mo) mice consumed ad libitum diets containing 0 or 1 g CLA /100 g for 8 wk. Splenocytes from half of the mice were isolated to evaluate proliferation to concanavalin A (Con A) (0.5, 1.5, 5.0 mg/L) and phytohemagglutinin A (PHA) (5, 20, 40 mg/L) and lipopolysaccharide (LPS) (5, 15, 30 mg/L), natural killer cell (NK) activity and prostaglandin (PG)E2 and interleukin (IL)-2 production. The remaining mice were used to evaluate in vivo delayed-type hypersensitivity (DTH) skin response. There was a significant decline due to age in response to all three mitogens tested (P < 0. 05). CLA supplementation significantly increased all CLA isomers measured in hepatic neutral lipids and phospholipids (P < 0.05). Young mice fed 1% CLA had greater splenocyte proliferation in response to Con A (0.5 and 5.0 mg/L) and PHA (40 mg/L) (P < 0.05) than young mice fed control diet. Old mice fed 1 g CLA/100 g had significantly higher proliferative response to optimal concentrations of Con A (1.5 mg/L) (P < 0.001) than the mice fed the control diet. Old mice fed the control diet had significantly lower splenocyte IL-2 production than the young mice (P < 0.005). CLA-supplemented young mice had significantly higher splenocyte IL-2 production than those fed the control diet (P < 0.05). CLA had no effect on NK cell activity, PGE2 production or DTH in young or old mice. Further studies are needed to determine the mechanism of CLA-induced enhancement of IL-2 production and T cell proliferation.

Aging↗
PubMed1999

The IMMUTANS variegation locus of Arabidopsis defines a mitochondrial alternative oxidase homolog that functions during early chloroplast biogenesis.

Nuclear gene-induced variegation mutants provide a powerful system to dissect interactions between the genetic systems of the nucleus-cytoplasm, the chloroplast, and the mitochondrion. The immutans (im) variegation mutation of Arabidopsis is nuclear and recessive and results in the production of green- and white-sectored leaves. The green sectors contain cells with normal chloroplasts, whereas the white sectors are heteroplastidic and contain cells with abnormal, pigment-deficient plastids as well as some normal chloroplasts. White sector formation can be promoted by enhanced light intensities, but sectoring becomes irreversible early in leaf development. The white sectors accumulate the carotenoid precursor phytoene. We have positionally cloned IM and found that the gene encodes a 40.5-kD protein with sequence motifs characteristic of alternative oxidase, a mitochondrial protein that functions as a terminal oxidase in the respiratory chains of all plants. However, phylogenetic analyses revealed that the IM protein is only distantly related to these other alternative oxidases, suggesting that IM is a novel member of this protein class. We sequenced three alleles of im, and all are predicted to be null. Our data suggest a model of variegation in which the IM protein functions early in chloroplast biogenesis as a component of a redox chain responsible for phytoene desaturation but that a redundant electron transfer function is capable of compensating for IM activity in some plastids and cells.

Amino Acid Sequence↗
PubMed1999

Estimating cortical potentials from scalp EEG's in a realistically shaped inhomogeneous head model by means of the boundary element method.

Cortical potentials are estimated from scalp potentials using a realistically shaped inhomogeneous head model, by means of the boundary element method (BEM). A new adaptive algorithm has been developed to achieve high accuracy to link directly the cortical potentials to the scalp potentials in a realistically shaped inhomogeneous head model including the thin low-conductivity skull layer. Computer simulations using a concentric three-spheres head model have tested this approach. The present study demonstrates that the cortical potentials can be directly estimated from the scalp potentials using the BEM in a realistically shaped inhomogeneous head model.

Algorithms↗
PubMed1999

Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4E.

The present study examined potential mechanisms for the inhibition of protein synthesis in skeletal muscle after chronic alcohol consumption. Rats were maintained on an alcohol-containing diet for 14 wk; control animals were pair fed. Alcohol-induced myopathy was confirmed by a reduction in lean body mass as well as a decrease in the weight of the gastrocnemius and psoas muscles normalized for tibial length. No alcohol-induced decrease in total RNA content (an estimate of ribosomal RNA) was detected in any muscle examined, suggesting that alcohol reduced translational efficiency but not the capacity for protein synthesis. To identify mechanisms responsible for regulating translational efficiency, we analyzed several eukaryotic initiation factors (eIF). There was no difference in the muscle content of either total eIF2alpha or the amount of eIF2alpha in the phosphorylated form between alcohol-fed and control rats. Similarly, the relative amount of eIF2Bepsilon in muscle was also not different. In contrast, alcohol decreased eIF2B activity in psoas (fast-twitch) but not in soleus or heart (slow-twitch) muscles. Alcohol feeding also dramatically influenced the distribution of eIF4E in the gastrocnemius (fast-twitch) muscle. Compared with control values, muscle from alcohol-fed rats demonstrated 1) an increased binding of the translational repressor 4E-binding protein 1 (4E-BP1) with eIF4E, 2) a decrease in the phosphorylated gamma-form of 4E-BP1, and 3) a decrease in eIF4G associated with eIF4E. In summary, these data suggest that chronic alcohol consumption impairs translation initiation in muscle by altering multiple regulatory sites, including eIF2B activity and eIF4E availability.

Adenosine Triphosphate↗
PubMed1999

Chronic alcohol feeding impairs hepatic translation initiation by modulating eIF2 and eIF4E.

The present study examined potential cellular mechanisms responsible for the inhibition of protein synthesis in liver after chronic alcohol consumption. Rats were maintained on an alcohol-containing diet for 14 wk; control animals were fed isocalorically. Hepatic ATP content was not different in alcohol-fed and control animals. No alcohol-induced reduction in total hepatic RNA content (an estimate of ribosomal RNA) was detected, suggesting that alcohol decreased translational efficiency. Alcohol feeding increased the proportion of 40S and 60S ribosomal subunits in the nonpolysome-associated fraction by 30%. To identify mechanisms responsible for the impairment in initiation, several eukaryotic initiation factors (eIF) were analyzed. Alcohol feeding decreased hepatic eIF2B activity by 36%. This reduction was associated with a 20% decrease in eIF2Bepsilon content and a 90% increase in eIF2alpha phosphorylation. Alcohol also dramatically influenced the distribution of eIF4E. Compared with pair-fed control values, alcohol feeding increased the amount of eIF4E present in the inactive 4E-binding protein 1 (4E-BP1). eIF4E complex by 80% and decreased binding of eIF4G to eIF4E by 70%. However, the phosphorylation status of 4E-BP1 and eIF4E was not altered by alcohol. Although the plasma concentrations of threonine, proline, and citrulline were mildly decreased, the circulating amount of total amino acids was not altered by alcohol feeding. In summary, these data suggest that chronic alcohol consumption impairs translation initiation in liver by altering eIF2B activity as well as eIF4F function via changes in eIF4E availability.

Adenosine Triphosphate↗
PubMed1999

The role of N-methyl-D-aspartate receptors in the release of adrenocorticotropin by dynorphin A1-13.

We previously reported that dynorphin A1-13 evokes a significant increase in plasma adrenocorticotropin (ACTH) after intravenous administration in the ovine fetus. This response was not sensitive to naloxone and was regulated differently from the response to U50, 488H, a selective kappa-opioid agonist. NMDA appears to play a role in many of the nonopioid actions of dynorphin. We therefore hypothesized that dynorphin A1-13 may release ACTH via N-methyl-D-aspartate (NMDA) receptors. To test this hypothesis, we have compared the ACTH response to dynorphin A1-13 and NMDA in the chronically-instrumented ovine fetus. Our data show that both dynorphin A1-13 (0.5 mg/kg) and NMDA (4 mg/kg) induced a significant release of immunoreactive ACTH in the late-term ovine fetus. The ACTH response to NMDA was of a smaller magnitude, but of longer duration, when compared to dynorphin A1-13. The response to both dynorphin A1-13 and NMDA was significantly attenuated by pretreatment with the noncompetitive NMDA antagonist, MK-801, but was not affected by antagonists of corticotropin-releasing hormone and arginine vasopressin. Finally, the ACTH response to both dynorphin A1-13 and NMDA were inhibited by dexamethasone. The results of this study indicate a role for NMDA receptors in the action of dynorphin A1-13, and suggest that NMDA may act directly at the level of the pituitary to release ACTH without the involvement of hypothalamic secretagogues.

Adrenocorticotropic Hormone↗
PubMed1999

Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes.

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c. ) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA. Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.

Animals↗
PubMed1999

C. elegans MAC-1, an essential member of the AAA family of ATPases, can bind CED-4 and prevent cell death.

In the nematode Caenorhabditis elegans, CED-4 plays a central role in the regulation of programmed cell death. To identify proteins with essential or pleiotropic activities that might also regulate cell death, we used the yeast two-hybrid system to screen for CED-4-binding proteins. We identified MAC-1, a member of the AAA family of ATPases that is similar to Smallminded of Drosophila. Immunoprecipitation studies confirm that MAC-1 interacts with CED-4, and also with Apaf-1, the mammalian homologue of CED-4. Furthermore, MAC-1 can form a multi-protein complex that also includes CED-3 or CED-9. A MAC-1 transgene under the control of a heat shock promoter prevents some natural cell deaths in C. elegans, and this protection is enhanced in a ced-9(n1950sd)/+ genetic background. We observe a similar effect in mammalian cells, where expression of MAC-1 can prevent CED-4 and CED-3 from inducing apoptosis. Finally, mac-1 is an essential gene, since inactivation by RNA-mediated interference causes worms to arrest early in larval development. This arrest is similar to that observed in Smallminded mutants, but is not related to the ability of MAC-1 to bind CED-4, since it still occurs in ced-3 or ced-4 null mutants. These results suggest that MAC-1 identifies a new class of proteins that are essential for development, and which might regulate cell death in specific circumstances.

Adenosine Triphosphatases↗
PubMed1999

Ethanol-induced apoptosis to stable HepG2 cell lines expressing human cytochrome P-4502E1.

In a previous study (Wu and Cederbaum, J. Biol. Chem. 271:23914-23919, 1996), ethanol was shown to be cytotoxic to HepG2 cells, which were transduced to express human cytochrome P-4502E1 (CYP2E1) but not to control HepG2 cells. The goal of the current study was to evaluate whether this toxicity was apoptotic in nature. Incubation of CYP2E1-expressing HepG2 cells with 100 mM ethanol for 2 days produced morphological changes and DNA fragmentation (in situ labeling, flow cytometry, and DNA ladder formation) indicative of apoptosis. No changes were observed in the control HepG2 cells that do not express CYP2E1. Ethanol-induced apoptosis was also observed in HepG2 cells transiently transfected to express CYP2E1. The ethanol-induced apoptosis was prevented by 4-methylpyrazole, an inhibitor of ethanol oxidation by CYP2E1, and by trolox, an antioxidant that prevents lipid peroxidation. Ethanol treatment of the cells expressing CYP2E1 resulted in increased activities of caspases 1 and 3. An inhibitor of these caspases prevented the ethanol-induced apoptosis in the stable cell lines and the transiently transfected cell lines. Ethanol did not cause apoptosis in a HepG2 cell line overexpressing bcl-2 plus CYP2E1, but did cause apoptosis in cell lines expressing CYP2E1 in the absence of bcl-2. These experiments demonstrate that ethanol can produce apoptosis in HepG2 cells that express CYP2E1. Increased production of reactive oxygen species and lipid peroxidation can be associated with apoptotic cell death. The prevention of the ethanol-induced apoptosis by 4-methylpyrazole and by trolox suggests that production of a prooxidative state as a consequence of ethanol oxidation by CYP2E1 results in eventual activation of caspases such as caspases 1 and 3, which can trigger the apoptotic process.

Antidotes↗
PubMed1999

[Loss of heterozygosity and microsatellite instability in laryngeal carcinoma near p16 gene].

OBJECTIVE: To search for the minimal overlap region of tumor suppressor gene in laryngeal carcinoma and discuss the correlation of p16 gene with laryngeal carcinogenesis. METHODS: Five microsatellite polymorphism markers near p16 gene were selected to detect loss of heterozygosity (LOH) and microsatellite instability (MI) in 60 cases of laryngeal squamous cell carcinoma. RESULTS: The frequencies of LOH in 5 markers were less than 23.1%, while the frequencies of MI in 2 markers were higher, with the highest frequency (46.1%) in D9S1752. CONCLUSION: The results suggest that the deletion of p16 gene does not play an important role in the laryngeal carcinogenesis and there may exist a gene around D9S1752 participating in the development of laryngeal carcinoma, which correlates with the mutation of repair gene.

Gene Deletion↗
PubMed1999

Comparison of clinical efficacy and adverse effects between extended-release felodipine and slow-release diltiazem in patients with isolated systolic hypertension.

BACKGROUND: Isolated systolic hypertension (ISH) is a risk factor for cardiovascular disease. Extended-release felodipine (felodipine ER) has been shown to be effective in the treatment of ISH in Caucasians. However, its pharmacological properties are different from another calcium blocker, diltiazem. Also, the effectiveness, tolerability, and adverse reactions of these two antihypertensive agents for ISH have not been thoroughly assessed in Chinese. METHODS: Sitting blood pressures (BP), heart rate, body weight, adverse reactions, and serum biochemistry were assessed in 70 patients with isolated systolic hypertension (34 treated with felodipine ER and 36 slow-release diltiazem [diltiazem SR] for 10 weeks). Each patient was given 5 mg of felodipine ER or 90 mg of diltiazem SR once daily and was doubled to twice daily if necessary. RESULTS: Five patients on felodipine ER and four on diltiazem SR withdrew because of intolerable side effects. By ten weeks, 67.6% of the patients responded to a daily dose of 5-10 mg of felodipine ER and 58.3% to a daily dose of 90-180 mg of diltiazem SR. At the end of treatment, felodipine ER lowered the mean BP from 187/83 mmHg at baseline to 149/74 mmHg, whereas diltiazem SR decreased the BP from 185/84 mmHg to 158/78 mmHg (not significant between the two groups). The heart rate did not change significantly in either group. Overall, these two groups of patients had the same rate of adverse reactions (50.0% vs. 50.0%) with similar profiles of the adverse effects. CONCLUSION: Equivalent doses of felodipine ER and diltiazem SR are effective first-line monotherapeutic agents for the treatment of ISH.

Adult↗
PubMed1999

Comparison of antihypertensive efficacy and tolerability of losartan and extended-release felodipine in patients with mild to moderate hypertension.

Appropriate control of blood pressure has been shown to reduce morbidity and mortality in patients with hypertension. Losartan potassium, a selective antagonist of the angiotensin II type 1 (AT1) receptor, has been shown to lower blood pressure in patients with hypertension. The purpose of this study was to compare the efficacy and tolerability of losartan and extended-release (ER) felodipine in Taiwanese patients with mild to moderate hypertension. Patients with mild to moderate hypertension (sitting diastolic blood pressure, 95-115 mm Hg) were enrolled in this prospective, randomized, parallel study. Sitting blood pressure, heart rate, adverse reactions, and serum biochemistry values were assessed during 2 weeks of placebo and 12 weeks of active treatment. Each patient received 50 mg of losartan or 5 mg of felodipine ER once daily, and the dosage was adjusted to double the initial level at week 6 if necessary. Of the 44 patients randomly allocated to receive losartan (n = 23) or felodipine (n = 21) therapy, 37 completed the study; three patients in the losartan group and four in the felodipine group withdrew because of adverse experiences, or were lost to follow-up. The mean reductions in sitting diastolic blood pressure at 6 and 12 weeks were significant with both losartan (-8.6 and -11.38 mm Hg, respectively) and felodipine (-9.2 and -10.69 mm Hg, respectively), and did not differ significantly between the two groups. Both losartan and ER felodipine were well tolerated by patients. However, the ER felodipine group had a significantly higher rate of drug-related flushing than the losartan group (24% vs 0%, p = 0.022). The results indicate that once-daily administration of losartan is as effective and well tolerated as once-daily ER felodipine in blood pressure reduction.

Adult↗
PubMed1999

[Study of superinfection of HBV and HCV].

OBJECTIVES: To understand the situation in hepatitis B patients coinciding with HCV and to explore its influence on HCV on the replication of HBV. METHODS: Using ELISA, 712 hepatitis B patients were tested for serum anti-HCV and markers of HBV. RESULTS: Of the 712 patients, anti-HCV positive rate was 14.47% with the highest 48.98% in patients with severe hepatitis and the lowest 3.25% in patients with acute hepatitis. Markedly different anti-HCV positive rates (P < 0.001) in patients of different clinical stages were discovered. The more severe the case with longer the course, the higher the anti-HCV positive rates. In patients with superinfection of HBV and HCV, serum HBsAg, HBeAg and anti-HBcIgM positive rates were lower than those in patients with hepatitis B (P < 0.001, P < 0.001 and P < 0.05) but the anti-HBe positive rates were higher. All the differences showed an obvious statistical significance. CONCLUSION: Hepatitis B coinciding with HCV infection is responsible for the deterioration of the disease and towards its formation of its chronic phase as well as for the inhibition of HBV replication.

Adolescent↗
PubMed1999

[Study on hepatitis G virus infection].

OBJECTIVE: To find out the situation of HGV infection in Shandong Province, and to explore the relations between HGV infection and HCV or HBV infection. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to determine the serum anti-HGV in 1,082 patients with viral hepatitis, 77 patients with non A-E hepatitis and 361 blood donors. RESULTS: 53 patients whose serum anti-HGVs were positive (positive rate: 3.49%) were noticed. The anti-HGV positive rate (8.93%) in patients with Hepatitis C was remarkably higher than that (3.32%) in patients with Hepatitis B (chi 2 = 8.80, P < 0.01). The anti-HGV positive rate (4.82%) in patients with chronic hepatitis was significantly higher than that (0.79%) in patients with acute hepatitis (chi 2 = 10.79, P < 0.01). The anti-HGV positive rate (8.00%) in patients with severe hepatitis was obviously higher than that in patients with acute hepatitis (chi 2 = 10.23, P < 0.01). CONCLUSION: The manifestations of HGV infection can be expressed as virus-carriers, subclinical infection or various clinical types. Patients with Hepatitis C were more subjective to be overlapped with HGV than the patients with Hepatitis B; moreover, HCV or HBV infection superinfected with HGV is associated with exacerbation of patients' condition and the formation of chronic infection.

Adolescent↗
PubMed1999

Laplacian electrocardiography.

This article reviews the recent development in Laplacian electrocardiography. The Laplacian electrocardiogram was proposed in the early 1990s as an alternative for mapping regional cardiac electrical activity. Considerable progress has been made in the field during the last 5 years on this emerging technique. This article attempts to cover both the basic concepts and theory for general readers in biomedical engineering, and state-of-the-art developments in forward and inverse problems of Laplacian electrocardiography, as well as Laplacian ECG mapping in an experimental setting for researchers working in the field of cardiac mapping. The article also addresses controversies regarding the feasibility of experimentally obtaining the Laplacian electrocardiogram in human subjects. The work reviewed in this article suggests that Laplacian electrocardiography merits further investigation and promises to provide an important alternative means of assessing noninvasively cardiac electrical activity.

Algorithms↗
PubMed1999

Effect of removal of external calcium on phosphoinositide hydrolysis in cultured myotubes of embryonic chicken.

The effect of removal of external Ca2+ on phosphoinositide hydrolysis was investigated in cultured myotubes from 9-day-old Leghorn embryonic chicken. In the myotubes exposed to Ca(2+)-free Ringer's solution, the turnover of phosphoinositide was exponentially decreased with a time constant of about 26 min. In the presence of external Ca2+, the hydrolysis of phosphoinositide was significantly increased by exposure to 80 mmol/L K+ solution. After removal of external Ca2+, 80 mmol/L K+ exposure caused a slight decrease of phosphoinositides hydrolysis in comparison with the control (normal Ringer). It is indicated that hydrolysis of phosphoinositide in cultured myotubes can be enhanced by high K+ exposure. External Ca2+ is essential for this effect, which is different from mature muscle fibres.

Animals↗
PubMed1999

[Identification of cDNA fragments related to alpha particles radiation induced neoplastic transformation of rat tracheal epithelial cells].

OBJECTIVE: To isolate genes involved in neoplastic transformation induced by alpha-particles. METHODS: The differential display technique was used to identify differentially expressed mRNA species between primary and neoplastic transformed rat tracheal epithelial (RTE) cells induced by alpha particles. RESULTS: 15 differentially displayed gene fragments were cloned and sequenced. Seven novel ESTs were submitted to GenBank. Homology searching revealed that clone ZG35 was highly homologous to rat Annexin I gene which was thought to be involved in mitogenic signal transduction as a substrate of epidermal growth factor receptor/kinase. Clone ZC52 was nearly identical to a novel rattus norvegicus gene for carboxylesterase precursor, clone ZG52 was 3' similar to human SRPK2 gene suggesting it may be a novel SRPK2 related gene involved in pre-mRNA splicing. Clone ZA73 was a novel gene fragments, and clone ZC66 was highly homologous to rat nucleoside diphosphate kinase gene or metastasis suppressor gene nm23, sequence analysis suggested that nm23 might be mutated in the transformed RTE cells. Northern hybridization confirmed the above gene or gene fragments to be up-regulated in the transformed RTE cells. CONCLUSION: These results provide clues to elucidate the mechanisms of radiation oncogenesis and suggest that Annexin I, carboxylesterase precursor gene, ZG52 and nm23 may be involved in the neoplastic transformation induced by alpha-particles radiation.

Alpha Particles↗