Search PubMed⌕ Search

Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 91 records · Page 5Linked to original sources
PubMed2001

Study of cyclin proteolysis in anaphase-promoting complex (APC) mutant cells reveals the requirement for APC function in the final steps of the fission yeast septation initiation network.

Cytokinesis in eukaryotic cells requires the inactivation of mitotic cyclin-dependent kinase complexes. An apparent exception to this relationship is found in Schizosaccharomyces pombe mutants with mutations of the anaphase-promoting complex (APC). These conditional lethal mutants arrest with unsegregated chromosomes because they cannot degrade the securin, Cut2p. Although failing at nuclear division, these mutants septate and divide. Since septation requires Cdc2p inactivation in wild-type S. pombe, it has been suggested that Cdc2p inactivation occurs in these mutants by a mechanism independent of cyclin degradation. In contrast to this prediction, we show that Cdc2p kinase activity fluctuates in APC cut mutants due to Cdc13/cyclin B destruction. In APC-null mutants, however, septation and cutting do not occur and Cdc13p is stable. We conclude that APC cut mutants are hypomorphic with respect to Cdc13p degradation. Indeed, overproduction of nondestructible Cdc13p prevents septation in APC cut mutants and the normal reorganization of septation initiation network components during anaphase.

Anaphase↗
PubMed2001

V. Stress and irritable bowel syndrome.

Different types of stress play important roles in the onset and modulation of irritable bowel syndrome (IBS) symptoms. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Animal models have recently been proposed that mimic key features of the human syndrome.

Animals↗
PubMed2001

Basic pathophysiologic mechanisms in irritable bowel syndrome.

Converging evidence supports the concept that the irritable bowel syndrome (IBS) symptom complex results from altered regulation of gastrointestinal motility and epithelial function, as well as an altered perception of visceral events. Despite similar symptoms, there is likely heterogeneity of underlying dysfunction and pathogenesis in different subgroups of IBS patients: the syndrome may be produced by primary alterations in the central nervous system (CNS; top down model), or by primary alterations in the periphery (bottom up model), or by a combination of both. One plausible mechanism by which alterations in the CNS result in symptoms, is the enhanced responsiveness of central stress/emotion circuits. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility, secretion, immune function and in alterations in the perceptual and emotional response to visceral events.

Animals↗
PubMed2001

c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis.

Mitogen-activated protein kinase (MAPK) cascades are involved in inflammation and tissue destruction in rheumatoid arthritis (RA). In particular, c-Jun N-terminal kinase (JNK) is highly activated in RA fibroblast-like synoviocytes and synovium. However, defining the precise function of this kinase has been difficult because a selective JNK inhibitor has not been available. We now report the use of a novel selective JNK inhibitor and JNK knockout mice to determine the function of JNK in synoviocyte biology and inflammatory arthritis. The novel JNK inhibitor SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) completely blocked IL-1--induced accumulation of phospho-Jun and induction of c-Jun transcription in synoviocytes. Furthermore, AP-1 binding and collagenase mRNA accumulation were completely suppressed by SP600125. In contrast, complete inhibition of p38 had no effect, and ERK inhibition had only a modest effect. The essential role of JNK was confirmed in cultured synoviocytes from JNK1 knockout mice and JNK2 knockout mice, each of which had a partial defect in IL-1--induced AP-1 activation and collagenase-3 expression. Administration of SP600125 modestly decreased the rat paw swelling in rat adjuvant-induced arthritis. More striking was the near-complete inhibition of radiographic damage that was associated with decreased AP-1 activity and collagenase-3 gene expression. Therefore, JNK is a critical MAPK pathway for IL-1--induced collagenase gene expression in synoviocytes and in joint arthritis, indicating that JNK is an important therapeutic target for RA.

Activating Transcription Factor 2↗
PubMed2001

Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex.

OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. CONCLUSIONS: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.

Adult↗
PubMed2001

Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.

OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant. METHOD: Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function. RESULTS: Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment. CONCLUSIONS: These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.

Adult↗
PubMed2001

Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers.

OBJECTIVE: Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells. METHOD: Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [(18)F]fluorodeoxyglucose. RESULTS: Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers. CONCLUSIONS: The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions.

Adult↗
PubMed2001

Brain proton magnetic resonance spectroscopy and imaging in children exposed to cocaine in utero.

OBJECTIVE: The effects of prenatal cocaine exposure have been examined using neurobehavioral and brain structural evaluations; however, no study has examined the effects of prenatal cocaine on brain metabolism. Proton magnetic resonance spectroscopy ((1)H-MRS) is a noninvasive method to examine the biochemistry of various brain regions. The purpose of this study was to examine the possible neurotoxic effects of prenatal cocaine exposure on the developing brain using (1)H-MRS. METHODS: Cocaine-exposed children (n = 14) and age-matched unexposed control participants (n = 12) were evaluated with MRI and localized (1)H-MRS. Metabolite concentrations of N-acetyl-containing compounds (NA), total creatine (Cr), choline-containing compounds, myoinositol, and glutamate + glutamine were measured in the frontal white matter and striatum. RESULTS: Despite an absence of structural abnormalities in either group, children exposed to cocaine in utero had significantly higher Cr (+13%) in the frontal white matter. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal in both regions examined by (1)H-MRS. Normal NA suggests no significant neuronal loss or damage in the 2 brain regions examined in children exposed to cocaine prenatally. CONCLUSIONS: Consistent with findings in abstinent adult cocaine users, we found increased Cr in the frontal white matter, with normal NA in children exposed to cocaine. These findings suggest the need to investigate further possible abnormalities of energy metabolism in the brain of children exposed to cocaine in utero. In addition, this study demonstrates the feasibility of using (1)H-MRS to investigate the effects of prenatal drug exposure on the developing brain.

Aspartic Acid↗
PubMed2001

AP-1--glucocorticoid receptor crosstalk taken to a higher level.

More than a decade ago our view of gene regulation by glucocorticoids (GC) and other steroid hormones underwent a dramatic change with the discovery of negative crosstalk (transcriptional interference) between the GC receptor (GCR) and transcription factor AP-1 (Jun:Fos). It was initially observed that induction of the collagenase type 1 gene, which is mediated through activation of AP-1 by growth factors and inflammatory cytokines, is repressed by GC. This repression was attributed to mutual negative interactions between AP-1 and GCR. Although the exact molecular mechanism underlying this particular case of transcriptional interference is yet to be determined, it has become clear that this and analogous interactions with other transcription factors (e.g. nuclear factor-kappaB) underlie the anti-inflammatory and immunosuppressive activity of GC. Recent studies conducted at the whole animal level indicate that the interactions between the AP-1 and GC signaling pathways are much more extensive. AP-1-related signaling via the Jun N-terminal kinases can lead to increased levels of circulating GC, which eventually down-modulate AP-1 activity via transcriptional interference. This negative feedback loop is likely to be of great importance for maintenance of homeostasis and regulation of stress responses, including acute and chronic inflammation.

Gene Expression Regulation↗
PubMed2001

[Isolation, purification and determination of polysaccharides X-C-3-III and X-C-3-IV from Angelica sinensis (Oliv) Diels].

Polysaccharides X-C-3-III and X-C-3-IV had been obtained from Angelica sinensis (Oliv) Diels. Their average MW were determined to be 85,000 and 65,765 by gel chromatography after the hydrolysates of X-C-3-III and X-C-3-IV, the compositions of them were identified by silanization method and capillary gas chromatography. X-C-3-III and X-C-3-IV are composed of galacose, arabinose, rhamnose, glucuronic acid and galacturonic acid. The molar ratio of those sugars were determined as 24.3:15.8:4.2:3.1:52.6 and 12.6:10.7:7.2:8.3:61.2, respectively.

Angelica sinensis↗
PubMed2001

Predicting soil-water partition coefficients for Hg(II) from soil properties.

The metal adsorption characteristics for fifteen Taiwan soils by Hg(II), were evaluated using pH as the major variable. The soil samples were thoroughly characterized for their physical chemical properties and composition, particularly organic matter and metal oxides. The adsorption of Hg(II) increased with increasing pH between pH 2.5 and 5.5, whereas the adsorption significantly decreased above around pH 5.5. Below pH 5.5, greater adsorption was found for soils with a higher organic matter content at constant pH and metal concentration. To better understand the mechanism of adsorption, the experimental results for Hg (II) were tested in a partition coefficient model to relate the adsorption of the Hg(II) by the different soils with soil components: organic matter, iron oxide, aluminium oxide and manganese oxide. This model was not successful when applied to measurements at the differing natural soil pHs because of the importance of pH. At pH greater than 5.5 the model fails because of the complexation of Hg by the dissolved organic matter. However, partition coefficients obtained from experimental data were highly correlated with those calculated for a partition coefficient between mercury and organic matter alone at lower pH. Normalization of the partition coefficients, Kd, for the organic matter content of the soils, Kom, greatly improved the correlation between the partition coefficient and pH under pH 5.5 (R2 increased from 0.484 to 0.716). This suggests that the surficial adsorption sites are principally due to organic matter for pH less than 5.5. For the 24-hour equilibration period employed, diffusion of Hg through this superficial organic matter coating to underlying sorptive materials, including metal oxides, is not important in the partitioning of Hg. At pH above 5, a decrease of mercury adsorption with increasing solution pH was also found. This result may be explained in part by the complexation of mercury by soil dissolved organic matter whose concentration increased with increasing pH.

Adsorption↗
PubMed2001

Human tenon's fibroblast-produced ifnbeta and the prevention of t-cell apoptosis.

PURPOSE: Fibroblast-T-cell interactions may contribute to the development of chronic inflammation, a risk factor for trabeculectomy failure. This study was undertaken to determine whether normal and growth-arrested human Tenon's fibroblasts (HTF) can prevent cytokine deprivation-mediated T-cell apoptosis through the secretion of interferon (IFN)beta. METHODS: HTF were used either untreated or pretreated with mitomycin-C (MMC; 0.1 or 0.4 mg/ml) or 5-fluorouracil (5FU; 25 or 50 mg/ml). IL2-deprived T cells were cocultured with HTF. T-cell viability was measured at specific time points. Human Tenon's fibroblast-conditioned medium was used either untreated or treated with a neutralizing antibody against IFNbeta to block its action, after which IL2-deprived T cells were added and T-cell viability was measured. An image analysis system was used to determine the production of IFNbeta by either untreated or MMC-treated HTF. RESULTS: T-cell viability was significantly greater when T cells were cocultured with both untreated and growth-arrested HTF than when T cells were cultured alone (day 7, P = 0.0001). Neutralizing the action of IFNbeta blocked HTF-mediated T-cell rescue from apoptosis. Both untreated and growth-arrested HTF secrete IFNbeta, and MMC at 0.4 mg/ml appeared to increase IFNbeta production. CONCLUSIONS: Cytokine deprivation-mediated T-cell apoptosis can be prevented by the action of IFNbeta secreted by both normal and growth-arrested HTF, which suggests that growth-arrested HTF can still participate in an aggressive wound-healing reaction by mediating a persistent inflammatory phase. This may partly explain why some trabeculectomies fail in high-risk patients, despite the use of antimetabolites.

Apoptosis↗
PubMed2001

[Production and cytogenetics of intergeneric hybrids between Ogura CMS Brassica campestris var. purpuraria and Raphanus sativus].

Crosses between Ogura CMS Brassica campestris var. purpuraria (AA, 2n = 20) and Raphanus sativus (RR, 2n = 18) were made and many intergeneric hybrids were produced. The F1 seedlings did not show chlorosis at low temperature. When red Raphanus sativus varieties were used as male parent, the leaf petiole and leaf vein of F1 plants were purple, and when white Raphanus sativus varieties were used as male parent, the leaf petiole and leaf vein of F1 plants were not purple. All the F1 plants had white flowers and normal honey glands. Male gametes of the F1 were highly sterile and female gametes of the F1 were partly fertile. Cytological studies indicated that chromosome number of the F1 was 2n = 19 as expected, the mean chromosome pairing pattern was 15.53 I + 1.34 II + 0.25 III + 0.01 IV. Most chromosomes exsistet as univalents, but there also exsisted some bivalents, trivalents and even tetravalents, suggesting that chromosome set A was partly homologous with chromosome set R.

Brassica↗
PubMed2001

Correlates of victimization in Chinese children's peer groups.

This study reports a cross-sectional investigation of the behavioral and academic correlates of victimization in Chinese children's peer groups. The participants were 296 children (161 boys and 135 girls; mean age = 11.5 years) from Tianjin, China. Multi-informant assessments (peer nominations, teacher ratings, and self-reports) of peer victimization, aggression, submissiveness-withdrawal, assertiveness-prosociability, and academic functioning were obtained. Structural equation models indicated that peer victimization was associated with poor academic functioning, submissive-withdrawn behavior, aggression, and low levels of assertive-prosocial behavior. These findings suggest that there is considerable similarity in the social processes underlying peer group victimization across Chinese and Western cultural settings.

Achievement↗
PubMed2001

Effects of recombinant human basic fibroblast growth factor on restenosis after arterial endothelial injury in rats.

AIM: To study the preventive effect of recombinant human basic fibroblast growth factor (rh-bFGF) on restenosis after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Sixty male Wistar rats were randomly divided into sham operation group, intima injured group, and intima injured plus rh-bFGF treated group. Rat carotid arteries were injured using a balloon catheter except sham operation group. The rats of rh-bFGF treated group were injected im rh-bFGF 10 kU . kg-1 . d-1 after intima was injured. Ten rats in each group were killed on d 7 and d 14 after injury, respectively. [3H]Thymidine incorporation assay and pathological examination were carried out to each vessel. RESULTS: (1) Seven days after injury, the average intimal thickness in sham operation group, intima injured group, and rh-bFGF treated group was (7 +/- 1), (32 +/- 11), and (17 +/- 3) micron; average intimal area was (384 +/- 145), (1530 +/- 817), and (586 +/- 185) micron2; the numbers of smooth muscle cells in neointima per transect were 0 +/- 0, 146 +/- 18, and 105 +/- 26; the ratio of the collagen area to intimal area plus medial area were 0.29 +/- 0.09, 0.7 +/- 0.3, and 0.30 +/- 0.14; [3H]thymidine incorporation were (17 +/- 6), (62 +/- 23), (20 +/- 8) kBq/g tissue, respectively. (2) Fourteen days after injury, the average intimal thickness of sham operation group, intima injured group, and rh-bFGF treated group was (8 +/- 1), (41 +/- 9), and (20 +/- 3) micron; average intimal area was (391 +/- 134), (1761 +/- 337), and (731 +/- 124) micron2; the numbers of smooth muscle cells in neointima per transect were 0 +/- 0, 145 +/- 9, and 102 +/- 6; the ratio of collagen area to intimal area plus medial area were 0.28 +/- 0.14, 0.59 +/- 0.21, and 0.38 +/- 0.03; [3H]thymidine incorporation was (15 +/- 4), (57 +/- 11), and (22 +/- 6) kBq/g tissue, respectively. CONCLUSION: Large dosage of rh-bFGF inhibits neointimal hyperplasia and reduces restenosis after balloon injury.

Angioplasty, Balloon, Coronary↗
PubMed2001

[Effect on the pregnant woman and fetus by multiple hepatitis virus infection].

OBJECTIVE: To evaluate the effect on the pregnant woman and fetus by infection of multiple hepatitis virus during pregnancy. METHODS: Hepatitis virus A, hepatitis virus B, hepatitis virus C, hepatitis virus D and hepatitis virus E were determined in the pregnant women with abnormal liver function during 1994-1999. Patients diagnosed to be infected by single hepatitis virus or multiple hepatitis virus were divided into two groups and complications of the pregnant woman and fetus and their prognosis were evaluated. RESULTS: There were no significant differences in the levels of alamine transaminase (ALT), aspartama transaminase (AST) and total bilirubin (TBIL) between the multiple hepatitis virus infection group (multiple group) and the single hepatitis virus infection group (single group) (P > 0.05). The positive rate of HbeAg (35.7%) in multiple group was significantly lower than in single group (P < 0.05). However, the positive rate of HbeAb (57.1%) in multiple group was significantly higher than in single group (P < 0.01). There were no significant differences in incidences of pregnancy induced hypertension (PIH), postpartum hemorrhage, serious symptoms and mortality between the multiple hepatitis virus infection group and the single hepatitis virus infection group (P > 0.05). However, the incidences of premature rupture of membrane (PROM), premature delivery, 28.1%, 25.0% fetal distress and newborn infant asphyxia 31.3%, 25.0% in multiple hepatitis virus infection group were significantly higher than in single hepatitis virus infection group (P < 0.05, P < 0.01). CONCLUSIONS: Multiple hepatitis virus infection during pregnancy has no more serious effect on the pregnant woman, but has worse effect on fetus than single hepatitis virus infection. The obstetrician should pay more attention to the health care of the pregnant woman with the multiple hepatitis virus infection to prevent PROM and premature delivery, at the same time monitor fetus carefully and deal with labor actively to decrease the mortality of the fetus.

Adult↗
PubMed2001

Regulation of osteopontin expression in a rat model of urolithiasis.

OBJECTIVE: To investigate the relationship between the expression and regulation of osteopontin (OPN) and urolithiasis. METHODS: Normal and stone model rats were treated with 1,25-dihydroxyvitamin D3(D3), vitamin K, testosterone or estradiol for 7 days, and the expression of osteopontin and its mRNA were detected with immunohistochemistry and Northern blot, respectively. Crystals deposited in rat kidneys were observed with a polarization microscope. The concentrations of crystal components in rat urine were determined. RESULTS: The results showed that vitamin K, testosterone and estradiol up-regulated the expression of OPN mRNA and its protein, thus decreasing the precipitation of calcium oxalate in rat kidneys. D3 increased the concentration of calcium in urine, and accelerated the sedimentation of calcium oxalate in rat kidneys. CONCLUSIONS: These findings indicate that OPN may be an important macromolecule in the normal endogenous inhibition of the formation of urolithiasis. Vitamin K, testosterone and estradiol inhibit the formation of stones via up-regulating the expression of OPN in kidneys, while D3 over dose may accelerate the process.

Animals↗