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Biomedical subjects

Q Guo

Publications and source records attributed to Q Guo.

At least 73 records · Page 4Linked to original sources
PubMed1999

Protein structure prediction in a 210-type lattice model: parameter optimization in the genetic algorithm using orthogonal array.

We have applied the orthogonal array method to optimize the parameters in the genetic algorithm of the protein folding problem. Our study employed a 210-type lattice model to describe proteins, where the orientation of a residue relative to its neighboring residue is described by two angles. The statistical analysis and graphic representation show that the two angles characterize protein conformations effectively. Our energy function includes a repulsive energy, an energy for the secondary structure preference, and a pairwise contact potential. We used orthogonal array to optimize the parameters of the population, mating factor, mutation factor, and selection factor in the genetic algorithm. By designing an orthogonal set of trials with representative combinations of these parameters, we efficiently determined the optimal set of parameters through a hierarchical search. The optimal parameters were obtained from the protein crambin and applied to the structure prediction of cytochrome B562. The results indicate that the genetic algorithm with the optimal parameters reduces the computing time to reach a converged energy compared to nonoptimal parameters. It also has less chance to be trapped in a local energy minimum, and predicts a protein structure which is closer to the experimental one. Our method may also be applicable to many other optimization problems in computational biology.

Algorithms↗
PubMed1999

Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice.

Excitotoxicity, a form of neuronal injury in which excessive activation of glutamate receptors results in cellular calcium overload, has been implicated in the pathogenesis of Alzheimer disease (AD), although direct evidence is lacking. Mutations in the presenilin-1 (PS1) gene on chromosome 14 are causally linked to many cases of early-onset inherited AD (refs. 5,6). We generated PS1 mutant mice (PS1M146VKI) that express the PS1 M146V targeted allele at normal physiological levels. Although PS1M146VKI mice have no overt mutant phenotype, they are hypersensitive to seizure-induced synaptic degeneration and necrotic neuronal death in the hippocampus. Cultured hippocampal neurons from PS1M146VKI mice have increased vulnerability to death induced by glutamate, which is correlated with perturbed calcium homeostasis, increased oxidative stress and mitochondrial dysfunction. Agents that suppress calcium influx or release and antioxidants protect neurons against the excitotoxic action of the PS1 mutation. These findings establish a direct link between a genetic defect that causes AD and excitotoxic neuronal degeneration, and indicate new avenues for therapeutic intervention in AD patients.

Animals↗
PubMed1999

Increased vulnerability of hippocampal neurons from presenilin-1 mutant knock-in mice to amyloid beta-peptide toxicity: central roles of superoxide production and caspase activation.

Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Overexpression of PS1 mutations in cultured PC12 cells increases their vulnerability to apoptosis-induced trophic factor withdrawal and oxidative insults. We now report that primary hippocampal neurons from PS1 mutant knock-in mice, which express the human PS1M146V mutation at normal levels, exhibit increased vulnerability to amyloid beta-peptide toxicity. The endangering action of mutant PS1 was associated with increased superoxide production, mitochondrial membrane depolarization, and caspase activation. The peroxynitrite-scavenging antioxidant uric acid and the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone protected hippocampal neurons expressing mutant PS1 against cell death induced by amyloid beta-peptide. Increased oxidative stress may contribute to the pathogenic action of PS1 mutations, and antioxidants may counteract the adverse property of such AD-linked mutations.

Alzheimer Disease↗
PubMed1999

ESR studies of ascorbic acid-dependent recycling of the vitamin E homologue Trolox by coenzyme Q0 in murine skin homogenates.

The recycling of Trolox, a water-soluble vitamin E homologue, by coenzyme Q0 (CoQ0) during Cu2+-initiated oxidation of ascorbate in mouse skin homogenates was investigated using electron spin resonance (ESR) spectroscopy. In a mixture containing CoQ0, Cu2+ and mouse skin homogenates, the ESR signal of CoQ0 semiquinone radical (CoQ0*-) appeared and declined with time; addition of Trolox accelerated the CoQ0*- signal decay. Only after the disappearance of the CoQ0*- signal was the appearance of the Trolox phenoxyl radical signal observed. In addition, the lifetime of the CoQ0*- signal and the length of the lag period during which the Trolox radical ESR signal could not be detected were dependent on the presence of Trolox, CoQ0 or Cu2+. The results suggest that CoQ0*-, formed by the interaction between CoQ0 and endogenous ascorbic acid (AscH-) in skin homogenates, regenerates Trolox from its phenoxyl radical.

Animals↗
PubMed1999

Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects.

Smad5 has been implicated as a downstream signal mediator for several bone morphogenetic proteins (BMPs). To understand the in vivo function of Smad5, we generated mice deficient in Smad5 using embryonic stem (ES) cell technology. Homozygous mutant embryos die between E9.5 and E11.5, and display variable phenotypes. Morphological defects are first detected at E8.0 in the developing amnion, gut and heart (the latter defect being similar to BMP-2 knockout mice). At later stages, mutant embryos fail to undergo proper turning, have craniofacial and neural tube abnormalities, and are edematous. In addition, several extraembryonic lesions are observed. After E9.0, the yolk sacs of the mutants contain red blood cells but lack a well-organized vasculature, which is reminiscent of BMP-4, TGF-beta1 and TGF-beta type II receptor knockout mice. In addition, the allantois of many Smad5 mutants is fused to the chorion, but is not well-elongated. A unique feature of the Smad5 mutant embryos is that ectopic vasculogenesis and hematopoiesis is observed in the amnion, likely due to mislocation of allantois tissue. Despite the expression of Smad5 from gastrulation onwards, and in contrast to knockouts of Smad2 and Smad4, Smad5 only becomes essential later in extraembryonic and embryonic development.

Animals↗
PubMed1999

[Study on esophageal motility and its effect by EVL in patients with esophageal varices].

OBJECTIVE: To investigate the esophageal motility and its effect by EVL in patients with cirrhotic esophageal varices. METHODS: LESP, LESR, PA, PD, PV and 24 h pH-monitoring were measured by PC Polygraf HR system in subjects of control and cases of esophageal varices before and after EVL. RESULTS: In varices group, PA, PD, and PV were significantly abnormal in comparison with those in control group (P < 0.001, 0.01, 0.01). There were pathologic acid-reflux in patients with esophageal varices. After EVL, PA, PV and acid-reflux were significantly recovered. CONCLUSION: Patients with esophageal varices suffer from the significant abnormal esophageal motility and acid-reflux. All of the abnormal changes can be recovered by EVL treatment.

Adult↗
PubMed1999

[Experimental study of oxygen supply and demand balance during total hepatectomy and partial liver replantation with venous bypass technique in young pigs].

OBJECTIVE: To investigate the changes of oxygen supply and demand balance during total hepatectomy and partial liver replantation(TCH and PLRP) with venous bypass technique in pigs. METHODS: Seven young pigs[weight (24.2 +/- 4.8) kg] were anesthetized with fentanyl and pentobartal. Catheters were inserted into portal vein via splenic vein and into vena cava inferior via right femoral vein, respectively, and the two catheters were connected by a "Y" adaptor to right atrium via extracorporeal circulation pump. Venous bypass technique was used during occlusion of total hepatic blood stream(OTHB). SvO2, hemodynamics and blood gas analysis were measured after anesthesia, during and 30 minutes after venous bypass. RESULTS: SvO2 was decreased significantly(P < 0.05), vein bypass technique ameliorated partially the disturbance of hemodynamics, and there was correlation between CO and SvO2 during THC and PLRP in pigs. CONCLUSION: The results suggest that there is oxygen supply and demand unbalance during THC and PLRP with venous bypass technique in pigs, and it is beneficial to monitor oxygen ladder during operation.

Animals↗
PubMed1999

[Effect of desflurane on quantitative electroencephalogram and hemodynamics].

To evaluate the feasibility of monitoring depth of desflurane anesthesia by quantitative electroencephalogram(QEEG) and hemodynamics, eight ASA I-II patients were studied. Anesthesia was induced by propofol and vecuronium, after tracheal intubation and the lungs were ventilated with desflurane in oxygen. The results showed that desflurane significantly reduced bispectral index(BI), 95% spectral edge frequency(SEF) and median frequency(MF) in a negative linear dose-related manner. When the end-tidal desflurane concentration reached 1.5 MAC, mean artery pressure(MAP) was decreased significantly, and heart rate(HR) increased by 14.5% (but there was no statistic significance), compared with pre-anesthesia. The results suggest that QEEG can be used to monitor depth of desflurane anesthesia, but MAP and HR are not the ideal monitoring indices during desflurane anesthesia.

Adult↗
PubMed1999

[Clinical observation on ondansetron in preventing nausea and vomiting after cholecystectomy under abdominoscope].

OBJECTIVE: To evaluate the prophylactic effect of ondansetron on postoperative nausea and vomiting (PONV) of cholecystectomy under abdominoscope. METHODS: Sixty patients, scheduled for selective cholecystectomy under abdominoscope, were randomly and double-blindly allocated to receive an intravenous bolus of either 0.9% NS 10 ml(Group placebo, n = 30) or 8 mg of ondansetron in 10 ml solution(Group ondansetron, n = 30), respectively. RESULTS: The incidences of nausea and vomiting in ondansetron group(33.3% and 26.7%) were significantly lower than those in placebo group(73.3% and 66.7%) (P < 0.05). Administration of ondansetron had no obvious effect on the mean arterial pressure, SpO2, and respiratory frequency. CONCLUSION: Ondansetron can be used effectively and safely to prevent PONV in cholecystectomy patients under abdominoscope.

Antiemetics↗
PubMed1999

[The absorption spectra of crystal thin film Cs3Cu2I5].

In this paper we measured the absorption spectra of crystal thin film Cs3Cu2I5 at room and liquid nitrogen temperatures, respectively, and calculated the excitonic coefficient of the material. The excitonic coupling energy deltaE(ex)(1) = (0.53 +/- 0.07) eV, excitonic radius a(ex) = 0. 326 nm,and forbidden zone width E(g) = (5.00 +/- 0.07) eV. The spectral analysis shows that the electron and exciton excitations of the Cs3Cu2I5 localize in the CuI subcrystal lattice, and reveals the law that governs the variance of the first excitonic peak position of the serial Cs(x)Cu(1-x) I compounds with their mol-components at low temperature.

English Abstract↗
PubMed1998

The star plot: an alternative display method for multivariate data in the analysis of food and drugs.

The star plot (SP) is a method of displaying multivariate data. It can be used to display data with more than two variables. Combined with principal component analysis (PCA), more than two PCs can be displayed in one plane. Different variants of this method are applied to an atomic absorption spectrometry (AAS) data set and to three near infra-red (NIR) spectral data sets. The results show that SP offers an easy way of visualising the multivariate data for food and drugs in a plane, and it is able to help the analyst to identify and to detect different qualities of food and drug composition. Moreover, when an object is added or removed, the PC's must be computed all over again, which is not the case for the SP-plot. The application of SP to the examples presented in the text suggests that the SP approach can be applied as an alternative method for displaying multivariate chemometric data in place of PCA or, to improve visualisation of the results already obtained with PCA.

Bread↗
PubMed1998

Identification of a large Myc-binding protein that contains RCC1-like repeats.

The protooncogene MYC plays an important role in the regulation of cellular proliferation, differentiation, and apoptosis and has been implicated in a variety of human tumors. MYC and the closely related MYCN encode highly conserved nuclear phosphoproteins (Myc and NMyc) that apparently function as transcription factors in the cell. We have identified a large and highly conserved nuclear protein that interacts directly with the transcriptional activating domain of Myc (designated "protein associated with Myc" or Pam). Pam contains an extended amino acid sequence with similarities to a protein known as regulator of chromosome condensation (RCC1), which may play a role in the function of chromatin. The gene encoding Pam (PAM) is expressed in all of the human tissue examined, but expression is exceptionally abundant in brain and thymus. Pam binds specifically to Myc, but not NMyc. The region in Myc required for binding to Pam includes a domain that is essential for the function of Myc and that is frequently mutated in Burkitt's lymphomas. PAM is located within a 300-kb region on chromosome 13q22.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Increased sensitivity to mitochondrial toxin-induced apoptosis in neural cells expressing mutant presenilin-1 is linked to perturbed calcium homeostasis and enhanced oxyradical production.

Many cases of autosomal dominant early onset Alzheimer's disease (AD) result from mutations in the gene encoding presenilin-1 (PS-1). PS-1 is an integral membrane protein expressed ubiquitously in neurons throughout the brain in which it is located primarily in endoplasmic reticulum (ER). Although the pathogenic mechanism of PS-1 mutations is unknown, recent findings suggest that PS mutations render neurons vulnerable to apoptosis. Because increasing evidence indicates that mitochondrial alterations contribute to neuronal death in AD, we tested the hypothesis that PS-1 mutations sensitize neurons to mitochondrial failure. PC12 cell lines expressing a PS-1 mutation (L286V) exhibited increased sensitivity to apoptosis induced by 3-nitropropionic acid (3-NP) and malonate, inhibitors of succinate dehydrogenase, compared with control cell lines and lines overexpressing wild-type PS-1. The apoptosis-enhancing action of mutant PS-1 was prevented by antioxidants (propyl gallate and glutathione), zVAD-fmk, and cyclosporin A, indicating requirements of reactive oxygen species (ROS), caspases, and mitochondrial permeability transition in the cell death process. 3-NP induced a rapid elevation of [Ca2+]i, which was followed by caspase activation, accumulation of ROS, and decreases in mitochondrial reducing potential and transmembrane potential in cells expressing mutant PS-1. The calcium chelator BAPTA AM and agents that block calcium release from ER and influx through voltage-dependent channels prevented mitochondrial ROS accumulation and membrane depolarization and apoptosis. Our data suggest that by perturbing subcellular calcium homeostasis presenilin mutations sensitize neurons to mitochondria-based forms of apoptosis that involve oxidative stress.

Adenosine Triphosphate↗
PubMed1998

Presenilin-1 mutation alters NGF-induced neurite outgrowth, calcium homeostasis, and transcription factor (AP-1) activation in PC12 cells.

Mutations in the presenilin-1 (PS-1) gene are responsible for many cases of autosomal dominant early-onset inherited Alzheimer's disease (AD). PS-1 is expressed in neurons where it is localized primarily to the endoplasmic reticulum (ER); the normal function of PS-1 and its pathogenic mechanism in AD are not known. We now report that expression of an AD-linked human PS-1 mutation (L286V) in PC12 cells results in aberrant differentiation responses to nerve growth factor (NGF). The extent of neurite outgrowth during a 10-day period of exposure to NGF was significantly reduced in lines stably expressing mutant PS-1. NGF induced a prolonged elevation of intracellular calcium levels which was significantly enhanced in cells expressing mutant PS-1. Induction of DNA binding activity of the transcription factor AP-1 by NGF was markedly suppressed in cells expressing mutant PS-1. Collectively, these findings demonstrate that a PS-1 mutation alters cellular signaling systems associated with NGF-induced differentiation in PC12 cells. Altered responsivity to neurotrophic factors could play a role in the pathogenesis of neuritic degeneration and cell death in human carriers of PS-1 mutations.

Animals↗
PubMed1998

Secreted beta-amyloid precursor protein counteracts the proapoptotic action of mutant presenilin-1 by activation of NF-kappaB and stabilization of calcium homeostasis.

Mutations in the presenilin-1 (PS-1) gene account for approximately 50% of the cases of autosomal dominant, early onset, inherited forms of Alzheimer's disease (AD). PS-1 is an integral membrane protein expressed in neurons and is localized primarily in the endoplasmic reticulum (ER). PS-1 mutations may promote neuronal degeneration by altering the processing of the beta-amyloid precursor protein (APP) and/or by engaging apoptotic pathways. Alternative processing of APP in AD may increase production of neurotoxic amyloid beta-peptide (Abeta) and reduce production of the neuroprotective alpha-secretase-derived form of APP (sAPPalpha). In differentiated PC12 cells expressing an AD-linked PS-1 mutation (L286V), sAPPalpha activated the transcription factor NF-kappaB and prevented apoptosis induced by Abeta. Treatment of cells with kappaB decoy DNA blocked the antiapoptotic action of sAPPalpha, demonstrating the requirement for NF-kappaB activation in the cytoprotective action of sAPPalpha. Cells expressing mutant PS-1 exhibited an aberrant pattern of NF-kappaB activity following exposure to Abeta, which was characterized by enhanced early activation of NF-kappaB followed by a prolonged depression of activity. Blockade of NF-kappaB activity in cells expressing mutant PS-1 by kappaB decoy DNA was associated with enhanced Abeta-induced increases of [Ca2+]i and mitochondrial dysfunction. Treatment of cells with sAPPalpha stabilized [Ca2+]i and mitochondrial function and suppressed oxidative stress by a mechanism involving activation of NF-kappaB. Blockade of ER calcium release prevented (and stimulation of ER calcium release by thapsigargin induced) apoptosis in cells expressing mutant PS-1, suggesting a pivotal role for ER calcium release in the proapoptotic action of mutant PS-1. Finally, a role for NF-kappaB in preventing apoptosis induced by ER calcium release was demonstrated by data showing that sAPPalpha prevents thapsigargin-induced apoptosis, an effect blocked by kappaB decoy DNA. We conclude that sAPPalpha stabilizes cellular calcium homeostasis and protects neural cells against the proapoptotic action of mutant PS-1 by a mechanism involving activation of NF-kappaB. The data further suggest that PS-1 mutations result in aberrant NF-kappaB regulation that may render neurons vulnerable to apoptosis.

Amyloid beta-Peptides↗