Biomedical subjects

W Duan

Publications and source records attributed to W Duan.

At least 37 records · Page 2Linked to original sources

PubMed2000

Selective protection and functionalization of morphine: synthesis and opioid receptor binding properties of 3-amino-3-desoxymorphine derivatives.

As part of an effort to identify novel opioid receptor interactive agents, we recently prepared a series of 8-(substituted)amino analogues of cyclazocine. We found the chiral 8-phenylamino (NHC(6)H(5)) cyclazocine derivative to have subnanomolar affinity for kappa opioid receptors and a 2-fold lower affinity for mu, opioid receptors. To determine if the benefits of (substituted)amino groups could be extended to the morphine core structure, we have made five novel 3-amino-3-desoxymorphine derivatives of general structure 5 where RR'N = H(2)N, CH(3)NH, (CH(3))(2)N, C(6)H(5)NH, and C(6)H(5)CH(2)NH. Relative to morphine, these derivatives had 38-273-fold, 11-41-fold, and 10-141-fold lower affinity for mu, delta, and kappa opioid receptors, respectively. Target compounds were made via Pd-catalyzed amination of a morphine 3-trifluoromethylsulfonate substrate where the 6-OH group was protected with a tert-butyldiphenylsilyl group. To make 6-tert-butyldiphenylsilyloxymorphine selectively, a new high-yield method was developed whereby morphine was bis-silylated using normal conditions followed by selective removal of the 3-tert-butyldiphenylsilyl group with catalytic tetrabutylammonium fluoride.

Adenylyl Cyclase Inhibitors↗

PubMed2000

8-Aminocyclazocine analogues: synthesis and structure-activity relationships.

Opioid binding affinities were assessed for a series of cyclazocine analogues where the prototypic 8-OH substituent of cyclazocine was replaced by amino and substituted-amino groups. For mu and kappa opioid receptors, secondary amine derivatives having the (2R,6R,11R)-configuration had the highest affinity. Most targets were efficiently synthesized from the triflate of cyclazocine or its enantiomers using Pd-catalyzed amination procedures.

Analgesics↗

PubMed2000

Participation of par-4 in the degeneration of striatal neurons induced by metabolic compromise with 3-nitropropionic acid.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by chorea, psychiatric disturbances, and dementia. It is caused by a polyglutamine repeat expansion in the huntingtin protein. The striatum is a major site of neuronal loss in HD, but the mechanisms underlying the neurodegenerative process have not been established. Systemic administration of the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP) to rodents results in motor dysfunction and degeneration of striatal neurons with features similar to those of HD. Here we report that levels of prostate apoptosis response-4 (Par-4; a protein recently linked to neuronal apoptosis) increase in striatum, and to a lesser extent in cortex and hippocampus, after systemic administration of 3NP to adult rats. The increase in Par-4 levels occurred within 6 h of 3NP administration and was followed by an increase in caspase activation which preceded neuronal loss. Exposure of cultured primary striatal neurons to 3NP induced a rapid increase of Par-4 levels and caspase activation. Treatment of striatal neurons with a Par-4 antisense oligonucleotide blocked Par-4 induction by 3NP, suppressed caspase activation, and attenuated neuronal apoptosis. The caspase-3 inhibitor DEVD suppressed 3NP-induced apoptosis of striatal neurons, but did not prevent induction of Par-4, indicating that Par-4 acts upstream of caspase-3 activation in the cell death pathway. Our results suggest that Par-4 plays an important role in the degeneration of striatal neurons in an experimental model of HD.

Animals↗

PubMed2000

Extra-pair paternity in waved albatrosses.

We estimated the rate of extra-pair fertilizations (EPFs) in waved albatrosses (Phoebastria irrorata) on Isla Española, Galápagos, Ecuador, using multilocus minisatellite DNA fingerprinting. Waved albatrosses are socially monogamous, long-lived seabirds whose main population is on Española. Aggressive extra-pair copulation (EPC) attempts have been observed in the breeding colony during the days preceding egg-laying. Our genetic analyses of 16 families (single chicks and their attending parents) revealed evidence of EPFs in four families. In all cases males were the excluded parent. These data suggest that waved albatrosses have an unusually high rate of EPF relative to taxa with similar life histories. Future behavioural observations will determine the extent to which forced vs. unforced EPCs contribute to this high EPF rate.

Animals↗

PubMed2000

Syntheses of 1-[(2-hydroxyethoxy)methyl]- and 1-[(1,3-dihydroxy-2-propoxy)methyl]- derivatives of 5-substituted-2,4-difluorobenzene: unnatural acyclo thymidine mimics for evaluation as anticancer and antiviral agents.

A group of 1-[(2-hydroxyethoxy)methyl]- (12) and 1-[(1,3-dihydroxy-2-propoxy)methyl]- (13) derivatives of 2,4-difluorobenzene possessing a variety of C-5 substituents (R = Me, H, I, NO2) were designed with the expectation that they may serve as acyclic 5-substituted-2'-deoxyuridine (thymidine) mimics. Compounds 12 and 13 (R = Me, H, I) were inactive as anticancer agents (CC50 = 10(-3) to 10(-4) M range), whereas the 5-nitro compounds (12d, 13d) exhibited weak-to-moderate cytotoxicity (CC50 = 10(-5) to 10(-6) M range) against a variety of cancer cell lines. All compounds prepared (12a-d, 13a-d) were inactive as antiviral agents in a broad-spectrum antiviral screen that also included the human immunodeficiency virus (HIV-1 and HIV-2) and herpes simplex virus (HSV-1 and HSV-2).

Animals↗

PubMed2000

Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats.

The adult brain contains neural stem cells that are capable of proliferating, differentiating into neurons or glia, and then either surviving or dying. This process of neural-cell production (neurogenesis) in the dentate gyrus of the hippocampus is responsive to brain injury, and both mental and physical activity. We now report that neurogenesis in the dentate gyrus can also be modified by diet. Previous studies have shown that dietary restriction (DR) can suppress age-related deficits in learning and memory, and can increase resistance of neurons to degeneration in experimental models of neurodegenerative disorders. We found that maintenance of adult rats on a DR regimen results in a significant increase in the numbers of newly produced neural cells in the dentate gyrus of the hippocampus, as determined by stereologic analysis of cells labeled with the DNA precursor analog bromodeoxyuridine. The increase in neurogenesis in rats maintained on DR appears to result from decreased death of newly produced cells, rather than from increased cell proliferation. We further show that the expression of brain-derived neurotrophic factor, a trophic factor recently associated with neurogenesis, is increased in hippocampal cells of rats maintained on DR. Our data are the first evidence that diet can affect the process of neurogenesis, as well as the first evidence that diet can affect neurotrophic factor production. These findings provide insight into the mechanisms whereby diet impacts on brain plasticity, aging and neurodegenerative disorders.

Animals↗

PubMed2000

[Relationship between flooded situation and poplar growth on beach land of Yangtze River in Anhui].

Through the analysis on the dynamics of flooding and the annual ring series of poplar trees on the beach land of Yangtze river in Anhui in the period of 1989-1997, the related models on flooded situation and ring growth were built. The results showed that there existed significant differences in flooding time and depth on different elevations of beach land, which made a great influence on the annual ring growth of poplar trees. The maximal flooded depth was more important than flooded time for its influence on ring growth. In addition, the flooded situation in August and September of previous year had a significantly negative influence on the ring growth of current year. The beach land with a maximal flooded depth of more than 2 m was not suitable for high-productive plantation of timber. It is suggested that a little more dense plantation should be managed for the production of pulp materials.

China↗

PubMed2000

[Damage to intra- and extrahepatic bile duct after hepatic artery embolization].

OBJECTIVE: To study the pathogenesis, treatment and prevention of bile duct damage arising from hepatic artery embolization. METHODS: Five patients with intra- and extrahepatic biliary damage resulting from hepatic artery embolization. Of these patients, 4 were due to hepatic artery embolization for hepatic haemangioma, and 1 was due to injecting TH (methacrylate) compound into the hepatic artery during operation. The hepatic artery was injected with ethanol so as to evaluate liver damage in experimental rats. RESULTS: All patients were found to have damage to intra- and extrahepatic bile duct at the hilum with biliary hepatocirrhosis; 4 of them received intrahepatic bile duct jejunal anastomosis and bile duct stent. Experiment result revealed obliteration of the bile duct and necrosis of the liver around the portal tract area. CONCLUSIONS: Arterial embolization of hepatic haemangioma may cause severe biliary damage.

Adult↗

PubMed2000

[A case-control study on the risk factors of esophageal cancer in Linzhou].

OBJECTIVE: To explore the characteristics of prevalence and influencing factors on the genesis of esophageal cancer. METHODS: A population-based 1:1 matched case-control study was conducted in Linzhou. A total number of 352 pairs of cases and controls matched on sex, age and neighborhoods. Data was analysed by SAS software to calculate the odds ratio of and to evaluate the relative risks. RESULTS: It was found that lower socio-economic status, environmental pollution around the residential areas, lampblack in room, lower body mass index (BMI), more pickled food intake, cigarette smoking, alcoholic drinking, vigor mental-trauma and depression were risk factors of esophageal cancer. It also showed that the subjects having had history of upper digestive tract operation, dysplasia of esophagus and family history of carcinoma markedly increased the risks of developing esophageal cancer. CONCLUSION: Esophageal cancer seemed to be resulted from the combination of genetic and environmental factor, hence called for of medical surveillance and comprehensive prevention.

Adult↗

PubMed2000

[Evaluation of modified maze procedure by Doppler tissue imager].

Since 1998 the cardiac surgeons of WCUMS have performed modified maze procedure for treating the patients with rheumatic mitral valve disease accompanied with chronic atrial fibrillation (Af). In this study, echocardiography, especially Doppler Tissue Imager (DTI), was used to evaluate atria contraction and function of such patients before and after the operation. 14 rheumatic mitral disease patients, aged 27-60 years, were chosen; among them, 11 had mitral stenosis, 3 mitral regurgitation. The control group consisted of 16 cases, aged 24-67 years, with normal echocardiogram. Before and half-1 year after the operation, left atrium, left ventricle, right atrium and ventricle were measured, and cardiac function and posterior wall motion of left atrium were measured. Velocity of mitral valve annual and tricuspid valve annual was measured in DTI. The results showed: There was no age difference between the two groups. The motion of posterior wall of left atrium was 4.18 +/- 0.37 mm in the operation group, 4.09 +/- 0.29 mm in the control group (P > 0.05). No difference in velocity of mitral/tricuspid valve annual between the two groups was observed; 3 peaks of mitral valve annual were S 0.11 +/- 0.02, e 0.11 +/- 0.01, a 0.09 +/- 0.01 (m/s) in operation group, and S 0.08 +/- 0.00, e 0.10 +/- 0.01, a 0.08 +/- 0.01 (m/s) in control group, (P > 0.05, respectively); 3 peaks of tricuspid valve annual were S 0.10 +/- 0.01 vs 0.11 +/- 0.08, e 0.11 +/- 0.08 vs 0.10 +/- 0.01, a 0.10 +/- 0.10 vs 0.09 +/- 0.01 (m/s), (P > 0.05, respectively). The diameter of left atrium after operation in cases of mitral stenosis decreased significantly, compared with that before operation (P < 0.01). The diameter of right atrium after operation decreased significantly, compared with that before operation (P < 0.01). There was no significant change in right ventricle/left ventricle/EF and FS. The diameter of left atrium after operation in cases of mitral regurgitation decreased significantly, compared with that before operation (P < 0.01). The diameter of left ventricle after operation decreased significantly, compared with that before operation (P < 0.05). No significant change in right ventricle/right atrium/EF and FS was noted. The authors conclude the DTI, as a new diagnostic method in echocardiography, has high sensitivity and is less influenced when used to observe motion of atrium-ventricle annual influenced. It can avoid the error caused by deviation of blood displacement. In the rheumatic mitral valve disease patients who had mitral valve replacement and modified maze procedure, atrial contraction respores, the risk of thromboembolism decreases and prognosis improves. So the operation is worth doing.

Adult↗

PubMed2000

[Preliminary echocardiographic evaluation on prosthetic valve replacement of preserving the subvalvular apparatus with artificial chorade for mitral stenosis].

The purpose of this study was to evaluate the preliminary results after prosthetic valve replacement of preserving the subvalvular apparatus with artificial chorade for mitral stenosis. 20 patients had received operation with expanded polytetrafluoroethylene(e-PTFE) as artificial chordade. The patients were followed up by means of echocardiography. The time of follow-up study varied from 4 to 18 months with a mean of 6 months. The left atrial, ventricular dimension as well as ventricular function were assessed. In addition, the length of artificial chorade and obstruction of left ventricular outflow track were observed. The results showed that left atrial diameter (LAD, from 57.59 +/- 13.51 mm to 47.05 +/- 9.55 mm), left ventricular end-diastolic dimension (LVEDD, from 46.23 +/- 12.56 mm to 42.41 +/- 10.86 mm), left ventricular end-systolic dimension (LVESD, from 33.50 +/- 10.20 mm to 29.68 +/- 8.40 mm) decreased (P < 0.01), and ejection fraction (EF, from 52.59 +/- 11.89% to 58.36 +/- 8.03%) increased (P < 0.05) after operation. There were no significant changes of fractional shortening (FS, from 29.23 +/- 8.99% to 31.05 +/- 6.08%). The length of artificial chorade ranged from 2.6 cm to 4.3 cm (the mean, 3.2 cm). There was no case of obstruction of left ventricular outflow track. It is believed that the result of preliminary echocardiographic observation on prosthetic valve replacement of preserving the subvalvular apparatus with artificial chorade for mitral stenosis is satisfactory.

Adult↗

PubMed1999

"Apoptotic" biochemical cascades in synaptic compartments: roles in adaptive plasticity and neurodegenerative disorders.

Apoptosis is a form of cell death historically defined by morphological and biochemical changes that occur in the cell body and nucleus. However, in contrast to nonneuronal cells in which apoptosis has been most intensively studied, neurons exhibit elaborate morphologies with synaptic connections often located at sites a great distance from the cell body. Signaling events occurring in synaptic terminals are believed to play important roles in either promoting (e.g., activation of glutamate receptors in postsynaptic spines) or preventing (e.g., activation of neurotrophic factors in presynaptic terminals) neuronal cell death in various physiological and pathological settings. We have found that apoptotic biochemical cascades can be activated locally in synaptic terminals and neurites and have shown that such cascades can result in local functional and morphological alterations and can also propagate to the cell body resulting in neuronal death. Prostate apoptosis response-4 production, caspase activation, loss of plasma membrane phospholipid asymmetry, mitochondrial dysfunction, and production of factors capable of inducing nuclear chromatin condensation and fragmentation can all occur locally in synaptic terminals in response to various stimuli. Activation of receptors for neurotrophic factors (e.g., basic fibroblast growth factor, secreted form of amyloid precursor protein alpha, and activity-dependent neurotrophic factor) and cytokines (e.g., tumor necrosis factor-alpha) in synaptic terminals can exert synaptoprotective actions that either can be transduced locally or may require signals to the nucleus and back. In addition to their roles in synaptic degeneration and neuron death, apoptotic cascades may play roles in synaptic plasticity. For example, we found that caspase activation can lead to proteolysis of certain glutamate receptor subunits and that this action of capases is correlated with reduced calcium responses to glutamate. We propose that apoptotic cascades function in a continuum in which low levels of activation play roles in adaptive responses to "stressors," whereas higher levels of activation mediate synaptic degeneration and cell death.

Animals↗

PubMed1999

Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease.

Parkinson's disease (PD) is an age-related disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN) and corresponding motor deficits. Oxidative stress and mitochondrial dysfunction are implicated in the neurodegenerative process in PD. Although dietary restriction (DR) extends lifespan and reduces levels of cellular oxidative stress in several different organ systems, the impact of DR on age-related neurodegenerative disorders is unknown. We report that DR in adult mice results in resistance of dopaminergic neurons in the SN to the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-induced loss of dopaminergic neurons and deficits in motor function were ameliorated in DR rats. To mimic the beneficial effect of DR on dopaminergic neurons, we administered 2-deoxy-D-glucose (2-DG; a nonmetabolizable analogue of glucose) to mice fed ad libitum. Mice receiving 2-DG exhibited reduced damage to dopaminergic neurons in the SN and improved behavioral outcome following MPTP treatment. The 2-DG treatment suppressed oxidative stress, preserved mitochondrial function, and attenuated cell death in cultured dopaminergic cells exposed to the complex I inhibitor rotenone or Fe2+. 2-DG and DR induced expression of the stress proteins heat-shock protein 70 and glucose-regulated protein 78 in dopaminergic cells, suggesting involvement of these cytoprotective proteins in the neuroprotective actions of 2-DG and DR. The striking beneficial effects of DR and 2-DG in models of PD, when considered in light of recent epidemiological data, suggest that DR may prove beneficial in reducing the incidence of PD in humans.

Animals↗

PubMed1999

Evolution of the ribosomal RNA internal transcribed spacer one (ITS-1) in cichlid fishes of the Lake Victoria region.

The nucleotide sequences of the first internal transcribed spacer (ITS-1) of the ribosomal RNA gene cluster have been determined for 11 species of closely related endemic cichlid fishes of the Lake Victoria region (LVR) and 6 related East African cichlids. The ITS-1 sequences confirmed independently derived basal phylogenies, but provide limited insight within this species flock. The line leading to Pseudocrenilabrus multicolor arose early, close to the divergence event that separated the tilapiine and haplochromine tribes of the "African Group" of the family Cichlidae. In this phylogeny, Astatoreochromis alluaudi and the riverine Astatotilapia burtoni are sister taxa, which together are a sister group to a monophyletic assemblage including both Lake Victoria and Lake Edward taxa. The ITS-1 data support the monophyly of haplochromine genera across lakes. Since Lake Victoria is believed to have been dry between 14, 500 and 12,400 BPE, the modern assemblage must have been derived from reinvasion by the products of earlier cladogenesis events. Thus, although the regional superflock is monophyletic, the haplochromines of Lake Victoria itself did not evolve in situ from a single ancestor.

Africa, Eastern↗

PubMed1999

Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice.

Alzheimer's disease is characterized by amyloid beta-peptide deposition, synapse loss, and neuronal death, which are correlated with cognitive impairments. Mutations in the presenilin-1 gene on chromosome 14 are causally linked to many cases of early-onset inherited Alzheimer's disease. We report that synaptosomes prepared from transgenic mice harboring presenilin-1 mutations exhibit enhanced elevations of cytoplasmic calcium levels following exposure to depolarizing agents, amyloid beta-peptide, and a mitochondrial toxin compared with synaptosomes from nontransgenic mice and mice overexpressing wild-type presenilin-1. Mitochondrial dysfunction and caspase activation following exposures to amyloid beta-peptide and metabolic insults were exacerbated in synaptosomes from presenilin-1 mutant mice. Agents that buffer cytoplasmic calcium or that prevent calcium release from the endoplasmic reticulum protected synaptosomes against the adverse effect of presenilin-1 mutations on mitochondrial function. Abnormal synaptic calcium homeostasis and mitochondrial dysfunction may contribute to the pathogenic mechanism of presenilin-1 mutations.

Alzheimer Disease↗

PubMed1999

Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration.

Synapses are often located at great distances from the cell body and so must be capable of transducing signals into both local and distant responses. Although progress has been made in understanding biochemical cascades involved in neuronal death during development of the nervous system and in various neurodegenerative disorders, it is not known whether such cascades function locally in synaptic compartments. Prostate apoptosis response-4 (Par-4) is a leucine zipper and death domain-containing protein that plays a role in neuronal apoptosis. We now report that Par-4 levels are rapidly increased in cortical synaptosomes and in dendrites of hippocampal neurons in culture and in vivo, following exposure to apoptotic or excitotoxic insults. Par-4 expression is regulated at the translational level within synaptic compartments. Par-4 antisense treatment suppressed mitochondrial dysfunction and caspase activation in synaptosomes and prevented death of cultured hippocampal neurons following exposure to excitotoxic and apoptotic insults. Local translational regulation of death-related proteins in synaptic compartments may play a role in programmed cell death, adaptive remodeling of synapses, and neurodegenerative disorders.

Animals↗

PubMed1999

Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases.

Synaptic degeneration and death of nerve cells are defining features of Alzheimer's disease (AD) and Parkinson's disease (PD), the two most prevalent age-related neurodegenerative disorders. In AD, neurons in the hippocampus and basal forebrain (brain regions that subserve learning and memory functions) are selectively vulnerable. In PD dopamine-producing neurons in the substantia nigra-striatum (brain regions that control body movements) selectively degenerate. Studies of postmortem brain tissue from AD and PD patients have provided evidence for increased levels of oxidative stress, mitochondrial dysfunction and impaired glucose uptake in vulnerable neuronal populations. Studies of animal and cell culture models of AD and PD suggest that increased levels of oxidative stress (membrane lipid peroxidation, in particular) may disrupt neuronal energy metabolism and ion homeostasis, by impairing the function of membrane ion-motive ATPases and glucose and glutamate transporters. Such oxidative and metabolic compromise may there-by render neurons vulnerable to excitotoxicity and apoptosis. Studies of the pathogenic mechanisms of AD-linked mutations in amyloid precursor protein (APP) and presenilins strongly support central roles for perturbed cellular calcium homeostasis and aberrant proteolytic processing of APP as pivotal events that lead to metabolic compromise in neurons. Specific molecular "players" in the neurodegenerative processes in AD and PD are being identified and include Par-4 and caspases (bad guys) and neurotrophic factors and stress proteins (good guys). Interestingly, while studies continue to elucidate cellular and molecular events occurring in the brain in AD and PD, recent data suggest that both AD and PD can manifest systemic alterations in energy metabolism (e.g., increased insulin resistance and dysregulation of glucose metabolism). Emerging evidence that dietary restriction can forestall the development of AD and PD is consistent with a major "metabolic" component to these disorders, and provides optimism that these devastating brain disorders of aging may be largely preventable.

Alzheimer Disease↗

PubMed1999

Participation of prostate apoptosis response-4 in degeneration of dopaminergic neurons in models of Parkinson's disease.

Dysfunction and death of midbrain dopaminergic neurons underlies the clinical features of Parkinson's disease (PD). Increasing evidence suggests roles for oxidative stress and a form of cell death called apoptosis in the pathogenesis of PD. We recently identified a 38-kd protein called prostate apoptosis response-4 (Par-4), which is rapidly induced in cultured neurons after exposure to apoptotic insults, and appears to play a necessary role in the cell death process. We now report that Par-4 levels increase dramatically in midbrain dopaminergic neurons of monkeys and mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The increase in Par-4 levels occurs in both neuronal cell bodies in the substantia nigra and their axon terminals in the striatum, and precedes loss of tyrosine hydroxylase immunoreactivity and cell death. In the monkey model, Par-4 levels were also increased in several brain regions (red nucleus, lateral geniculate nucleus, and cerebral cortex) in which functional alterations have previously been documented in PD patients and MPTP-treated monkeys. Exposure of cultured human dopaminergic neural cells to the complex I inhibitor rotenone, or to Fe2+, resulted in Par-4 induction, mitochondrial dysfunction, and subsequent apoptosis. Blockade of Par-4 induction by antisense treatment prevented rotenone- and Fe2+-induced mitochondrial dysfunction and apoptosis demonstrating a critical role for Par-4 in the cell death process. The data suggest that Par-4 may be involved in the neurodegenerative process in PD.

Animals↗