Search PubMed⌕ Search

Biomedical subjects

E Y Chen

Publications and source records attributed to E Y Chen.

At least 19 recordsLinked to original sources
PubMed2001

No association between T102C polymorphism of serotonin-2A receptor gene and clinical phenotypes of Chinese schizophrenic patients.

Serotonin dysfunction has been implicated in the pathogenesis of schizophrenia. Previous studies have shown an association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia. However, negative findings have also been reported. One possible explanation for such discrepancy is disease heterogeneity due to the current limitations in the diagnosis of schizophrenia. We conducted a case-control study of the T102C polymorphism with detailed characterisation of the clinical phenotypes to investigate the possible association with schizophrenia not only at the diagnostic level, but also with reference to other clinical phenotypes potentially related to serotonin dysfunction. Four hundred and seventy-one biologically unrelated schizophrenic patients and 523 unrelated healthy controls of Han Chinese descent in Hong Kong were compared for genotypes and allele frequencies of the T102C polymorphism by PCR amplification and restriction analysis. No evidence of association was detected at the diagnostic level and various clinical phenotypes. However, we found a trend association with small effect size between genotype 102T/102C and patients with better verbal fluency and less motor co-ordination soft neurological signs. There is a need for future large-scale studies on the possible associations between genetic polymorphisms and neurocognitive function impairments in schizophrenia.

Adolescent↗
PubMed2001

Hypoxia activates a platelet-derived growth factor receptor/phosphatidylinositol 3-kinase/Akt pathway that results in glycogen synthase kinase-3 inactivation.

Hypoxia initiates numerous intracellular signaling pathways important in regulating cell proliferation, differentiation, and death. In this study, we investigated the pathway that hypoxia uses to activate Akt and inactivate glycogen synthase kinase-3 (GSK-3), two proteins the functions of which are important in cell survival and energy metabolism. Severe hypoxia (0.01% oxygen) initiated a signaling cascade by inducing the tyrosine phosphorylation of the platelet-derived growth factor (PDGF) receptor within 1 h of treatment and increasing receptor association with the p85 subunit of phosphatidylinositol 3-kinase (PI 3-K). Hypoxia-induced signaling also resulted in PI 3-K-dependent phosphorylation of Akt on Ser-473, a modification of Akt that is important for its activation. This activation of Akt by hypoxia was substantially diminished in cells that possessed mutations in their PDGF receptor-PI 3-K interaction domain. In addition, Akt activation by hypoxia was resistant to treatment with the growth factor receptor poison suramin but was sensitive to treatment with the PI 3-K inhibitor wortmannin. Activation of Akt by hypoxia resulted in the phosphorylation of GSK-3alpha and GSK-3beta at Ser-9 and Ser-21, two well-documented Akt phosphorylation sites, respectively, that are inactivating modifications of each GSK-3 isoform. In support of the phosphorylation data, GSK-3 activity was significantly reduced under hypoxia. In conclusion, we propose that hypoxia activates a growth factor receptor/PI 3-K/Akt cascade that leads to GSK-3 inactivation, a pathway that can impact cell survival, proliferation, and metabolism.

Androstadienes↗
PubMed2001

Stroop interference and facilitation effects in first-episode schizophrenic patients.

In the Stroop test, interference occurs in naming the print color of a word when the word is itself the name of another color. Facilitation occurs when the word is the same as the print color. Previous studies on selective attention in schizophrenia using the Stroop interference effects have yielded contradicting results. Constraints included limited sample size and the recruitment of medicated chronic patients. We studied the Stroop interference and facilitation effects in a relatively large sample of first-episode schizophrenic patients (n=56), a substantial proportion of whom were medication-naïve (n=30) at the time of initial testing. We have also carried out longitudinal follow-up assessments when patients reached a clinically stable state, as well as 4months after recovery from the episode. We found that the Stroop interference effect was not increased in first-episode schizophrenic patients, whether medication-naïve or not. This effect did not change over the follow-up period. In addition, we detected an increase in Stroop facilitation effect in medicated schizophrenic patients, but only in the initial assessment soon after they had received medication. After sustained treatment, the increase in facilitation was normalized. These observations supported previous findings of a normal Stroop interference effect amongst schizophrenic patients. The increased facilitation effect for patients in their early phase of treatment (but not later) may represent an acute effect of anti-psychotic medication. Its nature and significance require further investigation.

Adult↗
PubMed2001

Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production.

Mitochondrial defects, which occur in the brain of late-stage Huntington's disease (HD) patients, have been proposed to underlie the selective neuronal loss in the disease. To shed light on the possible role of mitochondrial energy impairment in the early phases of HD pathophysiology, we carried out Golgi impregnation and quantitative histochemical/biochemical studies in HD full-length cDNA transgenic mice that were symptomatic but had not developed to a stage in which neuronal loss could be documented. Golgi staining showed morphologic abnormalities that included a significant decrease in the number of dendritic spines and a thickening of proximal dendrites in striatal and cortical neurons. In contrast, measurements of mitochondrial electron transport Complexes I-IV did not reveal changes in the striatum and cerebral cortex in these mice. Examination of the neostriatum and cerebral cortex in human presymptomatic and pathological Grade 1 HD cases also showed no change in the activity of mitochondrial Complexes I-IV. These data suggest that dendritic alterations precede irreversible cell loss in HD, and that mitochondrial energy impairment is a consequence, rather than a cause, of early neuropathological changes.

Animals↗
PubMed2001

Neurological signs and sustained attention impairment in schizophrenia.

Both neurological signs and attention impairments are often found in schizophrenia. This study addresses the extent to which neurological signs are related to sustained attention impairment. We assessed subgroups of neurological signs using the standardised Cambridge Neurological Inventory (CNI). Sustained attention was measured using a monotone counting paradigm. After taking into consideration potential confounds such as age, education level and duration of illness, we explored the correlation between sustained attention and groups of neurological signs, as well as with individual signs. We found that "motor coordination" and "disinhibition" signs were significantly related to sustained attention. The correlation with "sensory integration" just failed to reach significance after correction for multiple comparison. "Dyskinesia", "catatonia", "pyramidal" and "extrapyramidal" subgroups were unrelated to sustained attention. The results support the notion of heterogeneity and diversity in neurological signs (even among soft neurological signs) and argue against the use of a single global measure to embrace all soft neurological signs in schizophrenia.

Attention↗
PubMed2001

Insight changes in acute psychotic episodes: a prospective study of Hong Kong Chinese patients.

Insight impairment occurs commonly in psychotic disorders (including mood episodes with psychotic symptoms). The aim of the present study is to measure changes of insight over the course of a psychotic episode and to investigate its relationships with symptoms and neurocognitive functions, as well as psychosocial factors. Insight was assessed at weekly intervals in 80 consecutive inpatients presenting with a psychotic episode by using a Chinese translation of the Scale to Assess Unawareness of Mental Disorder (SUMD). The relationships between insight change and other variables were explored. Modest but significant changes in insight were found in both directions with clinical resolution of psychotic symptoms. In particular, insight "declined" as symptoms improved in a number of patients. In addition, changes in insight score correlated with changes in Wisconsin Card Sorting Test (WCST) performance. More changes in insight (in either direction) tended to occur in younger patients. These results indicated that adequate control of psychotic symptoms and improvement in neuropsychological functioning might be associated with better insight recovery.

Acute Disease↗
PubMed2001

University students' attitudes towards mental patients and psychiatric treatment.

BACKGROUND: Public attitudes towards mental patients and psychiatric treatment are mostly unfavorable. Mental patients tend to conceal their illness or selectively disclose their treatment histories to someone they trust. AIMS: To examine the university students' attitudes towards different information regarding a person labeled as mentally ill. METHODS: We designed seven descriptions of a mentally ill person of varying past and current treatment histories and randomly assigned 308 university undergraduates to read one of the descriptions. Subjects rated their willingness to interact with the hypothetical case using a 19-item social distance scale. RESULTS: Greater social distance was associated with non-medical field of study, no previous contact with the mentally ill and female gender. Subjects without previous contact with mentally ill individuals kept greater distance from a discharged mental patient receiving psychiatric care than a mental patient who did not require medications nor psychiatric follow-up. In contrast, respondents who had previous contact with the mentally ill were more willing to interact with a discharged mental patient receiving psychiatric care comparing with a person labeled as mentally ill alone and a mental patient who had never been admitted to hospital. CONCLUSIONS: Implications of our findings in clinical management and designing stigma-reducing programme are discussed.

Adult↗
PubMed2000

B2 bradykinin receptor immunoreactivity in rat brain.

Bradykinin has long been known to exist in the central nervous system and has been hypothesized to mediate specific functions. Despite an increasing understanding of the functions of bradykinin, little is known about the cell types expressing the bradykinin receptor within the brain. The present investigation employed a monoclonal antibody directed against the 15-amino-acid portion of the C-terminal of the human bradykinin B2 receptor to establish the cellular distribution of bradykinin B2 receptor immunoreactivity in the rat brain. Bradykinin B2 receptor immunoreactivity was ubiquitously and selectively observed in neurons, including those within the olfactory bulb, cerebral cortex, hippocampus, basal forebrain, basal ganglia, thalamus, hypothalamus, cerebellum, and brainstem nuclei. Bradykinin B2 receptor immunoreactivity was also present in the circumventricular organs including choroid plexus, subfornical organ, median eminence, and area postrema. Double-labeling experiments colocalizing the bradykinin B2 receptor with the neuronal marker NeuN or the astrocytic marker glial fibrillary acidic protein revealed that virtually 100% of the bradykinin B2 receptor-immunoreactive positive cells were neurons. The widespread distribution of bradykinin B2 receptor immunoreactivity in neuronal compartments suggests a greater than previously appreciated role for this peptide in neuronal function.

Amygdala↗
PubMed2000

Age-related decreases in GTP-cyclohydrolase-I immunoreactive neurons in the monkey and human substantia nigra.

Guanosine triphosphate cyclohydrolase I (GTPCHI) is a critical enzyme in catecholamine function and is rate limiting for the synthesis of the catecholamine co-factor tetrahydrobiopterin. The present study assessed the distribution of GTPCHI immunoreactivity (-ir) within the monkey and human ventral midbrain and determined whether its expression is altered as a function of age. Light and confocal microscopic analyses revealed that young monkeys and humans displayed GTPCHI-ir within melanin-containing and tyrosine-hydroxylase-ir neurons in primate substantia nigra. Stereological counts revealed that there was a 67.4% reduction in GTPCHI-ir neuronal number, a 63.5% reduction in GTPCHI-ir neuronal density, and a 37.6% reduction in neuronal volume in aged monkeys relative to young cohorts. Similar age-related changes were seen in humans, in whom there were significant reductions in the number of GTPCHI-ir nigral neurons in middle age (58.4%) and aged (81.5%) cases relative to young cohorts. The density of GTPCHI-ir neurons within the nigra was similarly reduced in middle-aged (63.0%) and aged (81.8%) cases. In contrast to monkeys, aged humans did not display shrinkage in the volume of GTPCHI-ir nigral neurons. The presence of numerous melanin-positive, but GTPCHI-ir immunonegative, neurons in the aged monkey and human nigra indicates that these decreases represent an age-related phenotypic downregulation of this enzyme and not a loss of neurons per se. These data indicate that there is a dramatic decrease in GTPCHI-ir in nonhuman primates and humans as a function of age and that loss of this enzyme may be partly responsible for the age-related decrease in dopaminergic tone within nigrostriatal systems.

Adolescent↗
PubMed2000

Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.

Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

The complete sequence of the mucosal pathogen Ureaplasma urealyticum.

The comparison of the genomes of two very closely related human mucosal pathogens, Mycoplasma genitalium and Mycoplasma pneumoniae, has helped define the essential functions of a self-replicating minimal cell, as well as what constitutes a mycoplasma. Here we report the complete sequence of a more distant phylogenetic relative of those bacteria, Ureaplasma urealyticum (parvum biovar), which is also a mucosal pathogen of humans. It is the third mycoplasma to be sequenced, and has the smallest sequenced prokaryotic genome except for M. genitalium. Although the U. urealyticum genome is similar to the two sequenced mycoplasma genomes, features make this organism unique among mycoplasmas and all bacteria. Almost all ATP synthesis is the result of urea hydrolysis, which generates an energy-producing electrochemical gradient. Some highly conserved eubacterial enzymes appear not to be encoded by U. urealyticum, including the cell-division protein FtsZ, chaperonins GroES and GroEL, and ribonucleoside-diphosphate reductase. U. urealyticum has six closely related iron transporters, which apparently arose through gene duplication, suggesting that it has a kind of respiration system not present in other small genome bacteria The genome is only 25.5% G+C in nucleotide content, and the G+C content of individual genes may predict how essential those genes are to ureaplasma survival.

Adenosine Triphosphate↗
PubMed2000

PLAC1, an Xq26 gene with placenta-specific expression.

A novel human X-linked gene shows placenta-specific expression and has been named PLAC1. The gene maps 65 kb telomeric to HPRT at Xq26 and has been completely sequenced at the cDNA and genomic levels. The mouse orthologue Plac1 maps to the syntenically equivalent region of the mouse X chromosome. In situ hybridization studies with the antisense mRNA during mouse embryogenesis detect Plac1 expression from 7.5 dpc (days postcoitum) to 14.5 dpc in ectoplacental cone, giant cells, and labyrinthine trophoblasts. The putative human and murine PLAC1 proteins are 60% identical and 77% homologous. Both include a signal peptide and a peptide sequence also found in an interaction domain of the ZP3 (zona pellucida 3) protein. These results make PLAC1 a marker for placental development, with a possible role in the establishment of the mother-fetus interface.

Amino Acid Sequence↗
PubMed2000

Cystic fibrosis transmembrane conductance regulator has an altered structure when its maturation is inhibited.

Inefficient maturation and trafficking to the cell surface of the cystic fibrosis transmembrane conductance regulator (CFTR) is the primary cause of cystic fibrosis. CFTR protein that fails to mature accumulates as an immature core-glycosylated protein and is rapidly degraded. To determine how the structures of mature and immature CFTR are different, we compared the properties of CFTR that had been expressed in the presence or absence of the proteasome inhibitor, MG-132 (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal). Transient expression of wild-type CFTR in the presence of submicromolar concentrations of MG-132 blocks maturation of the protein. We found that expression of CFTR in the presence of MG-132 trapped the protein in a trypsin-sensitive conformation. In addition, the structure of the carboxyl-terminus of immature and mature CFTR differed as histidine-tagged mature CFTR was preferentially recovered by metal-chelate chromatography. No chloride channel activity was detected when membranes containing immature CFTR were fused with planar lipid bilayers. These results show that expression of CFTR in the presence of MG-132 traps the protein in an altered conformation that may be inactive.

Amino Acid Sequence↗