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Biomedical subjects

K Chen

Publications and source records attributed to K Chen.

At least 19 recordsLinked to original sources
PubMed1999

Cerebral cortical blood flow maps are reorganized in MAOB-deficient mice.

Cerebral cortical blood flow (CBF) was measured autoradiographically in conscious mice without the monoamine oxidase B (MAOB) gene (KO, n=11) and the corresponding wild-type animals (WILD, n=11). Subgroups of animals of each genotype received a continuous intravenous infusion over 30 min of phenylethylamine (PEA), an endogenous substrate of MAOB, (8 nmol g-1 min-1 in normal saline at a volume rate of 0.11 microl g-1 min-1) or saline at the same volume rate. Maps of relative CBF distribution showed predominance of midline motor and sensory area CBF in KO mice over WILD mice that received saline. PEA enhanced CBF in lateral frontal and piriform cortex in both KO and WILD mice. These changes may reflect a differential activation due to chronic and acute PEA elevations on motor and olfactory function, as well as on the anxiogenic effects of this amine. In addition to its effects on regional CBF distribution, PEA decreased CBF globally in KO mice (range -31% to -41% decrease from control levels) with a lesser effect in WILD mice. It is concluded that MAOB may normally regulate CBF distribution and its response to blood PEA.

Animals↗
PubMed1999

Lack of protection from ischemic injury of monoamine oxidase B-deficient mice following middle cerebral artery occlusion.

Adult male wild-type mice received intraperitoneal (i.p.) administration of saline (n = 9) or 10 mg/kg L-deprenyl (n = 9) three times a week for 3 weeks. Mice with targeted inactivation of the monoamine oxidase B (MAO-B) gene received i.p. administration of saline (n = 8). Animals underwent ligation of the left common and external carotid arteries, followed by cauterization of the ipsilateral middle cerebral artery. Twenty-four hours post-surgery, all groups showed right torsion of the torso but no evidence of limb weakness, lateral instability, or circling. Ischemic changes were assessed from digitized video-images of serial sections of the brain stained with Hematoxylin/Eosin. No significant group differences were detected in infarct volume (14-18% of ipsilateral cortex) or in the extent of brain edema (4-7% increase in ipsilateral hemispheric swelling with respect to contralateral side). Our results suggest that absence of the MAO-B gene or inhibition of the enzyme with L-deprenyl are not protective or detrimental in an animal model of acute cortical infarction.

Animals↗
PubMed1999

Movement and reaction times and fine coordination tasks following pallidotomy.

The effect of a unilateral, microelectrode-guided lesion in the globus pallidum internum (GPi) was evaluated in 41 patients (21 women) with moderately advanced Parkinson's disease (PD). The mean age was 60.3+/-9.0 years (range, 40-74) and the mean symptom duration was 14.7+/-5.3 years (range, 4-25). In addition to clinical ratings, movement time (MT) and reaction time (RT) tests were performed at baseline and 3 months after surgery during the "practically defined off" state (more than 12 hours after the last dose of levodopa). Improvement occurred bilaterally with more robust and statistically significant improvement on the contralateral side in all RT tests. Simple reaction time (SRT) improved by 14.5% (p<0.001) and the choice reaction time (CRT) by 12.2% (p<0.001) when the arm contralateral to the pallidotomy side was tested. There was a trend toward improvement in the ipsilateral arm. The MT, determined by repetitive movement between two adjacent targets, improved by 24% contralaterally (p<0.0001) and by 12% ipsilaterally (p<0.005). In addition, the Purdue Pegboard (PP) test scores, used to evaluate hand dexterity, improved on the contralateral side by 35.5% (p<0.0002) but there was no statistically significant ipsilateral improvement. To the extent that MT and RT are quantitative measures of bradykinesia, our study provides evidence that this parkinsonian feature improves after pallidotomy.

Adult↗
PubMed1999

Visceral adipose tissue is not increased in Pima Indians compared with equally obese Caucasians and is not related to insulin action or secretion.

Pima Indians are insulin resistant and hyperinsulinaemic compared with Caucasians. We investigated whether abdominal fat distribution was different between Pimas and Caucasians and whether differences in the amount of visceral fat explained metabolic differences between the groups. Total body fat (absorptiometry) and abdominal fat distribution at L4-L5 (magnetic resonance imaging) were compared in 20 Pima Indians (10 men/10 women) and 20 age-, sex- and BMI-matched Caucasians. Insulin action was measured as glucose disposal during a two-step hyperinsulinaemic-euglycaemic glucose clamp and insulin secretion was assessed in response to oral and intravenous glucose tolerance tests. By design, percent body fat was similar in Pimas and Caucasians. Abdominal visceral and subcutaneous adipose tissue areas were also similar in the two groups (151+/-16 vs 139+/-15 cm2 and 489+/-61 vs 441+/-7 cm2 respectively). Plasma insulin concentrations were higher in Pimas than Caucasians in the fasting state (27+/-6 vs 11+/-2 mU/ml; p < 0.01) and after a 75-g oral glucose load (area under the curve 19975+/-2626 vs 9293+/-1847 mU x l(-1) x 180 min(-1); p < 0.005). Glucose disposal was lower in Pimas than Caucasians during both steps of the clamp and negatively correlated (after adjustment for percent body fat and sex) with visceral adipose tissue in Caucasians (partial r = -0.51, p = 0.03), but not in Pima Indians (r = -0.03, p = 0.92). Insulin secretion was not related to visceral fat independently of percent body fat in either group. We conclude that a relative increase in visceral fat does not explain insulin resistance and hyperinsulinaemia in Pima Indians.

Adipose Tissue↗
PubMed1999

Inhibition of copper-induced LDL oxidation by vitamin C is associated with decreased copper-binding to LDL and 2-oxo-histidine formation.

Oxidatively modified low-density lipoprotein (LDL) has numerous atherogenic properties, and antioxidants that can prevent LDL oxidation may act as antiatherogens. We have previously shown that vitamin C (L-ascorbic acid, AA) and its two-electron oxidation product dehydro-L-ascorbic acid (DHA) strongly inhibit copper (Cu)-induced LDL oxidation. These findings are unusual, as AA is known to act not only as an antioxidant, but also a pro-oxidant in the presence of transition metal ions in vitro, and DHA has no known reducing capacity. Here we report that human LDL (0.4 mg protein/ml) incubated with 40 microM Cu2+ binds 28.0 +/- 3.3 Cu ions per LDL particle (mean +/- SD, n = 10). Co-incubation of LDL with AA or DHA led to the time- and concentration-dependent release of up to 70% of bound Cu, which was associated with the inhibition of LDL oxidation. Incubation of LDL with Cu and AA or DHA also led to the time-dependent formation of 2-oxo-histidine, an oxidized derivative of histidine with a low affinity for Cu. Addition of free histidine prevented the formation of the LDL-Cu complexes and inhibited LDL oxidation, despite the fact that Cu remained redox-active. Interestingly, histidine was more effective than AA or DHA at limiting Cu binding to LDL, but at low concentrations AA and DHA were more effective than histidine at inhibiting LDL oxidation. These data suggest that there are at least two types of Cu binding sites on LDL: those that bind Cu in a redox-active form critical for initiation of LDL oxidation, and those that bind Cu in a redox-inactive form not contributing to LDL oxidation. The former sites may be primarily histidine residues of apolipoprotein B-100 that are oxidized to 2-oxo-histidine in the presence of Cu and AA or DHA, thus explaining, at least in part, the unusual inhibitory effect of vitamin C on Cu-induced LDL oxidation.

Antioxidants↗
PubMed1999

Schizophrenia, monoamine oxidase activity, and cigarette smoking.

Reduced monoamine oxidase activity has been proposed as a marker for vulnerability to schizophrenia. Reduced monamine oxidase activity has also been shown to occur in cigarette smokers. This study compared monamine oxidase activity level in a matched group of patients with schizophrenia who smoked with a group who did not. Lower levels of monoamine oxidase activity were found in the smokers and this is the likely explanation for the low levels hypothesized as a marker for schizophrenia.

Adult↗
PubMed1998

Transcription factor binding to the core promoter of the human monoamine oxidase B gene in the cerebral cortex and in blood cells.

Many studies show that monoamine oxidase B in blood cells is a biological marker for personality characteristics such as sensation seeking. The mechanism underlying this association is so far not explored. In the present study we have performed electrophoretic mobility-shift assays to investigate the pattern of protein binding to a 150 bp fragment of the proximal 5'-flanking region of the human monoamine oxidase B gene. We compared the pattern using nuclear extracts from human brain and lymphocytes. Interestingly, a correlation was observed between monoamine oxidase B enzyme activity in blood cells (platelets) and the binding pattern of two uncharacterized transcription factors. These data are well in line with the long-standing notion that interindividual differences in platelet monoamine oxidase may represent differences in expression of the enzyme rather than genotypic variation.

Blood Platelets↗
PubMed1998

Morphologic characteristics of physiologically defined neurons in the cat trigeminal nucleus principalis.

Although the principalis nucleus (Vp) contains trigeminothalamic and internuclear tract cells, the functional and morphologic differences between the two kinds of neurons have remained unsettled. The present study was aimed to address these problems by using the intracellular horseradish peroxidase injection technique in the cat. Of 20 neurons stained, 7 and 13 were located in the dorsomedial subnucleus (Vpd) and ventrolateral subnucleus (Vpv) of Vp, respectively. The Vpd neurons received input from the intraoral structures only but the Vpv neurons from the intraoral or facial structures. Nineteen neurons could be divided as class I and class II, based on the branching pattern of their stem axons. Class I (eight neurons) had an ascending stem axon without branching. Class II was divided into two subclasses (IIa and IIb). Class IIa (eight neurons) had an ascending stem axon from which branches were given off. Their branches formed a local-circuit restricted to the lower brainstem. Class IIb (three neurons) had a stem axon that formed the local-circuit only. The dendritic morphology was indistinguishable between different classes of neurons and between the subdivisions. Although the dendritic arborization pattern was governed by the location of the somata, it was suggested to be also important elements for determining primary afferent arborizations. In the brainstem nuclei, the jaw-closing motor nucleus received the highest density of projections from class II neurons with the receptive field involving the periodontal ligaments. The present study provides new findings that Vp neurons could be divided into three distinct populations and suggests that each population exerts a distinct function with respect to sensory discrimination, sensorimotor reflexes, or both.

Anatomy, Artistic↗
PubMed1998

Protease-activated receptor 1 (PAR-1) is required and rate-limiting for thrombin-enhanced experimental pulmonary metastasis.

Thrombin-treated tumor cells induce a metastatic phenotype in experimental pulmonary murine metastasis. Thrombin binds to a unique protease-activated receptor (PAR-1) that requires N-terminal proteolytic cleavage for activation by its tethered end. A 14-mer thrombin receptor activation peptide (TRAP) of the tethered end induces the same cellular changes as thrombin. Four murine tumor cells (Lewis lung, CT26 colon CA, B16F10 melanoma, and CCL163 fibroblasts) contain PAR-1, as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). B16F10 cells did not contain the two other thrombin receptors, PAR-3 and glycoprotein Ib. TRAP-treated B16F10 tumor cells enhance pulmonary metastasis 41- to 48-fold (n = 17). Thrombin-treated B16F10 cells transfected with full-length murine PAR-1 sense cDNA (S6, S7, S14, and S22) enhanced their adhesion to fibronectin 1.5- to 2.4-fold (n = 5, P <.04), whereas thrombin-treated wild-type cells do not. S6 (adhesion index, 1.5-fold) and S14 (index, 2.4-fold) when examined by RT-PCR and Northern analysis showed minimal expression of PAR-1 for S6 over wild-type and considerable expression for S14. Immunohistochemistry showed greater expression of PAR-1 for S14 compared with wild-type or empty-plasmid transfected cells. In vivo experiments with the thrombin-treated S14 transfectant showed a fivefold to sixfold increase in metastases compared with empty-plasmid transfected thrombin-treated naive cells or S6 cells (n = 20, P =.0001 to .02). Antisense had no effect on thrombin-stimulated tumor mass. Thus, PAR-1 ligation and expression enhances and regulates tumor metastasis.

Animals↗
PubMed1998

Simulation of Particle Adsorption onto a Polymer-Coated Surface Using the Dissipative Particle Dynamics Method.

Dissipative particle dynamics (DPD) was originated as a tool for performing fluid dynamics simulations of complex fluids and among other things has been used to simulate dilute polymer solutions. This report describes a new application of the technique-modeling the adsorption of colloidal particles onto a polymer-coated surface. This type of simulation would be beyond the scope of molecular dynamics but is effectively modeled with DPD. The preliminary results of these investigations, presented here, show good agreement with what might be predicted theoretically. They show that the colloidal particles would be less likely to adsorb onto the surface as the size of the polymer relative to the particle is increased, or similarly as the density of the polymers is increased. They also show that particle adsorption is reduced when the polymer is well solvated. They demonstrate how particles that have agglomerated with each other find it more difficult to penetrate a polymer barrier because of their greater size. Further investigation is required to understand the effects of temperature. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

H+ISFET-based biosensor for determination of penicillin G.

A biosensor based on an H+ ion sensitive field effect transistor (H+(-)ISFET) and penicillin G acylase has been developed. The response time of the sensor to different concentrations of penicillin G was 30 s. In a 20 mM phosphate buffer at pH 7.0, the linear range of the calibration curve was from 0.5 to 8 mM. The coefficients of variation for three samples with 20 repeated measurements were below 5%. Stability of the sensor could reach about 6 months and more than 1000 runs were performed without a significant decrease of the output value. The sensor was tested for measurement of the penicillin G content in penicillin fermentation both. Forty samples with low and high concentrations of penicillin G were chosen for the correlation test. The values assayed by the sensor method were compared with the values assayed by HPLC method, the correlation coefficient (r) was 0.9944 and the regression equation was y = 1.034X - 2083.7, respectively. The different measuring methods are discussed in the text.

Biosensing Techniques↗
PubMed1998

Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth.

Mxi1 belongs to the Mad (Mxi1) family of proteins, which function as potent antagonists of Myc oncoproteins. This antagonism relates partly to their ability to compete with Myc for the protein Max and for consensus DNA binding sites and to recruit transcriptional co-repressors. Mad(Mxi1) proteins have been suggested to be essential in cellular growth control and/or in the induction and maintenance of the differentiated state. Consistent with these roles, mxi1 may be the tumour-suppressor gene that resides at region 24-26 of the long arm of chromosome 10. This region is a cancer hotspot, and mutations here may be involved in several cancers, including prostate adenocarcinoma. Here we show that mice lacking Mxi1 exhibit progressive, multisystem abnormalities. These mice also show increased susceptibility to tumorigenesis either following carcinogen treatment or when also deficient in Ink4a. This cancer-prone phenotype may correlate with the enhanced ability of several mxi1-deficient cell types, including prostatic epithelium, to proliferate. Our results show that Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner.

Aging↗
PubMed1998

Mathematical model of the fission yeast cell cycle with checkpoint controls at the G1/S, G2/M and metaphase/anaphase transitions.

All events of the fission yeast cell cycle can be orchestrated by fluctuations of a single cyclin-dependent protein kinase, the Cdc13/Cdc2 heterodimer. The G1/S transition is controlled by interactions of Cdc13/Cdc2 and its stoichiometric inhibitor, Rum1. The G2/M transition is regulated by a kinase-phosphatase pair, Wee1 and Cdc25, which determine the phosphorylation state of the Tyr-15 residue of Cdc2. The meta/anaphase transition is controlled by interactions between Cdc13/Cdc2 and the anaphase promoting complex, which labels Cdc13 subunits for proteolysis. We construct a mathematical model of fission yeast growth and division that encompasses all three crucial checkpoint controls. By numerical simulations we show that the model is consistent with a broad selection of cell cycle mutants, and we predict the phenotypes of several multiple-mutant strains that have not yet been constructed.

Anaphase↗
PubMed1998

Predictors of cessation of marijuana use: an event history analysis.

Event history analysis was applied to monthly life and drug histories of a representative community sample of 706 marijuana users, followed from ages 15-16 to 34-35, to investigate factors associated with cessation of marijuana use from adolescence to adulthood. In addition to age and gender, the most important determinants of cessation are the phenomenology of marijuana use, social role participation, depressive symptoms and deviance. Frequent users, those who started using early and those who use illicit drugs other than marijuana are more likely to continue their marijuana use. Using marijuana for social reasons accelerates cessation, using to change one's mood reduces cessation. Becoming pregnant and a parent is the most important social role leading to marijuana cessation for women. There is also a very important experimental effect of the interview itself on the reported timing of a cessation. The effect of a social context favorable to marijuana use appears to reflect selection rather than social influence.

Adolescent↗
PubMed1998

A multicenter investigation with interphase fluorescence in situ hybridization using X- and Y-chromosome probes.

Twenty-six laboratories used X and Y chromosome probes and the same procedures to process and examine 15,600 metaphases and 49,400 interphases from Phaseolus vulgaris-leucoagglutinin (PHA)-stimulated lymphocytes. In Part I, each laboratory scored 50 metaphases and 200 interphases from a normal male and a normal female from its own practice. In Part II, each laboratory scored 50 metaphases and 200 interphases on slides prepared by a central laboratory from a normal male and a normal female and three mixtures of cells from the male and female. In Part III, each laboratory scored 50 metaphases (in samples of 5, 10, 15, and 20) and 100 interphases (in samples of 5, 10, 15, 20, and 50) on new, coded slides of the same specimens used in Part II. Metaphases from male specimens were scored as 98-99% XY with no XX cells, and 97-98% of interphases were scored as XY with 0.04% XX cells. Metaphases from female specimens were scored as 96-97% XX with 0.03% XY cells, and 94-96% of interphases were scored as XX with 0.05% XY cells. Considering the data as a model for any probe used with fluorescence in situ hybridization (FISH), a statistical approach assessing the impact of analytical sensitivity on the numbers of observations required to assay for potential mosaicisms and chimerisms is discussed. The workload associated with processing slides and scoring 50 metaphases and 200 interphases using FISH averaged 27.1 and 28.6 minutes, respectively. This study indicates that multiple laboratories can test/develop guidelines for the rapid, efficacious, and cost-effective integration of FISH into clinical service.

Cytogenetics↗
PubMed1998

The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53.

The INK4a gene encodes two distinct growth inhibitors--the cyclin-dependent kinase inhibitor p16Ink4a, which is a component of the Rb pathway, and the tumor suppressor p19Arf, which has been functionally linked to p53. Here we show that p19Arf potently suppresses oncogenic transformation in primary cells and that this function is abrogated when p53 is neutralized by viral oncoproteins and dominant-negative mutants but not by the p53 antagonist MDM2. This finding, coupled with the observations that p19Arf and MDM2 physically interact and that p19Rrf blocks MDM2-induced p53 degradation and transactivational silencing, suggests that p19Arf functions mechanistically to prevent MDM2's neutralization of p53. Together, our findings ascribe INK4a's potent tumor suppressor activity to the cooperative actions of its two protein products and their relation to the two central growth control pathways, Rb and p53.

Animals↗