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Lan Ma

Publications and source records attributed to Lan Ma.

44 records · Page 3Linked to original sources
PubMed2002

Quantifying robustness of biochemical network models.

BACKGROUND: Robustness of mathematical models of biochemical networks is important for validation purposes and can be used as a means of selecting between different competing models. Tools for quantifying parametric robustness are needed. RESULTS: Two techniques for describing quantitatively the robustness of an oscillatory model were presented and contrasted. Single-parameter bifurcation analysis was used to evaluate the stability robustness of the limit cycle oscillation as well as the frequency and amplitude of oscillations. A tool from control engineering--the structural singular value (SSV)--was used to quantify robust stability of the limit cycle. Using SSV analysis, we find very poor robustness when the model's parameters are allowed to vary. CONCLUSION: The results show the usefulness of incorporating SSV analysis to single parameter sensitivity analysis to quantify robustness.

Biochemical Phenomena↗
PubMed2002

Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation.

Chemotaxis mediated by chemokine receptors such as CXCR4 plays a key role in lymphocyte homing and hematopoiesis as well as in breast cancer metastasis. We have demonstrated previously that beta-arrestin2 functions to attenuate CXCR4-mediated G protein activation and to enhance CXCR4 internalization. Here we show further that the expression of beta-arrestin2 in both HeLa and human embryonic kidney 293 cells significantly enhances the chemotactic efficacy of stromal cell-derived factor 1alpha, the specific agonist of CXCR4, whereas the suppression of beta-arrestin2 endogenous expression by antisense or RNA-mediated interference technology considerably attenuates stromal cell-derived factor 1alpha-induced cell migration. Expression of beta-arrestin2 also augmented chemokine receptor CCR5-mediated but not epidermal growth factor receptor-mediated chemotaxis, indicating the specific effect of beta-arrestin2. Further analysis reveals that expression of beta-arrestin2 strengthened CXCR4-mediated activation of both p38 MAPK and ERK, and the suppression of beta-arrestin2 expression blocked the activation of two kinases. Interestingly, inhibition of p38 MAPK activation (but not ERK activation) by its inhibitors or by expression of a dominant-negative mutant of p38 MAPK effectively blocked the chemotactic effect of beta-arrestin2. Expression of a dominant-negative mutant of ASK1 also exerted the similar blocking effect. The results of our study suggest that beta-arrestin2 can function not only as a regulator of CXCR4 signaling but also as a mediator of stromal cell-derived factor 1alpha-induced chemotaxis and that this activity probably occurs via the ASK1/p38 MAPK pathway.

Adenoviridae↗
PubMed2002

Hippocampal long-term potentiation is reduced by chronic opiate treatment and can be restored by re-exposure to opiates.

Chronic exposure to opiates eventually leads to drug addiction, which is believed to involve maladaptive changes in brain function, but the underlying neuronal mechanisms remain primarily unknown. Given the known effects of opiates such as morphine and heroin on hippocampal function, we investigated the potential effect of chronic opiate treatment on long-term potentiation (LTP) at CA1 synapses in rat hippocampus, a leading experimental model for studying synaptic plasticity. Our results revealed that chronic exposure of rats to morphine or heroin, which induced severe drug tolerance and dependence, markedly reduced the capacity of hippocampal CA1 LTP during the period of drug withdrawal (from approximately 190% in control to approximately 120%). More interestingly, the capacity of LTP could be restored to the normal level by re-exposure of the animals to opiates, indicating that the synaptic function was already adapted to opiates. Morris water maze test, which measures behavioral consequences of synaptic plasticity, showed parallel learning deficits after chronic exposure to opiates. Moreover, the opiate-reduced LTP could also be restored by inhibitors of cAMP-dependent protein kinase A (PKA), suggesting that upregulation of cAMP pathway was likely one of the underlying mechanisms of the observed phenomena. These findings demonstrated that chronic opiate treatment can significantly modulate synaptic plasticity in the hippocampus, leading to an opiate dependence of the plasticity.

Animals↗
PubMed2002

[Observation on treatment of ectopic pregnancy by combination therapy of Chinese herbal medicine with mifepristone or methotrexate].

OBJECTIVE: To find a simpler, effectiver with less side-effect method for treatment of ectopic pregnancy. METHODS: One hundred and fourteen patients of ectopic pregnancy were divided into two groups, the 56 patients in Group A were treated with Mifepristone and Chinese herbal medicine (CHM), and 58 patients in Group B were treated with Methotrexate and CHM. The therapeutic effect in both groups was observed and compared. RESULTS: The rate of success in Group A was 82.14% and in Group B 70.69%, comparison between them showed no significance (P > 0.05). Time for successful treatment was 14.54 +/- 5.87 days in Group A and 9.00 +/- 5.09 days in Group B, comparison of them showed significant difference (P < 0.01). Insignificance revealed in comparison between the occurrence of side-effects for the groups, such as nausea, vomiting, diarrhea, liver dysfunction and lowering of white blood cells, but significance was shown in re-menstruation time (43.43 +/- 1.77 days vs 38.38 +/- 1.13 days, P < 0.05). CONCLUSION: Treatments of combined CHM with Mifepristone or Methotrexate showed similar therapeutic effect in treating ectopic pregnancy, but the latter showed a quicker initiation and less side-effects in delaying the re-menstruation time.

Abortifacient Agents↗
PubMed2001

Reactivation of morphine conditioned place preference by drug priming: role of environmental cues and sensitization.

RATIONALE: Relapse is a major characteristic of drug addiction and remains the primary problem in treating drug abuse. Despite a great deal of research, the exact factors that determine renewed drug-seeking and persistent craving for them remain unclear. OBJECTIVE: The present study was designed to evaluate the role of environmental cues and behavioral sensitization in reactivation of place preference following long-term extinction of morphine conditioned place preference (CPP) in rats. METHODS: After being injected with morphine and saline alternately for 6 days to induce morphine CPP, the rats were subjected to extinction of conditioning for 21 days. The rats were then administered various doses of morphine, heroin, or cocaine and confined in the previous drug- or saline-paired compartment. CPP was determined. Some rats were treated with scopolamine or naloxone prior to administration of these three drugs. RESULTS: Morphine CPP disappeared following a 21-day extinction. A single injection of morphine, heroin, or cocaine evoked place preference for the previous drug-paired side. However, place preference for the previous vehicle-paired side was induced after the animals received a single injection of morphine, heroin or cocaine and confined to the previous vehicle-paired compartment. Administration of naloxone prior to drug treatment significantly attenuated the place preference induced by morphine or heroin, but had no significant effect on the place preference elicited by cocaine. Administration of the cholinergic antagonist scopolamine before morphine, heroin and cocaine inhibited the expression of place preference. CONCLUSIONS: Environment-related cues and behavioral sensitization play critical roles in the incentive motivation underlying drug-seeking behaviors.

Animals↗
PubMed1999

Expression, Purification and Characterization of Regulatory Subunit of Type I cAMP-dependent Protein Kinase in E.coli.

Regulatory subunit of type I cAMP-dependent protein kinase (RI) possesses two cAMP-binding sites with high affinity for cAMP. In the current study, human RI cDNA fragment coding for residue 93-381 was cloned from neuronal cells. After subcloning into pET30a, the recombinant RI was expressed in E.coli BL21. Considerable amount of soluble RI subunit was produced in BL21 upon induction of IPTG. RI was purified to homogeneity over 95% after His-bind metal chelation chromatography. Approximately 8 mg pure RI was obtained from 0.1 liter of BL21 culture. Human RI prepared with this method binds to cAMP specifically and therefore can be used in cAMP assay.

Journal Article↗
PubMed1999

Differential and Tissue-specific Expression of Mitochondrial Elongation Factor Tu and Ts during Development.

The mitochondrial elongation factors Tu and Ts (EF-Tu(mt) and EF-Ts(mt)) are nuclear gene-encoded mitochondrial proteins and play important roles in growth and development. We prepared antibodies against EF-Tu(mt) and EF-Ts(mt) using purified recombinant EF-Tu(mt) and EF-Ts(mt). Western analysis indicates EF-Tu(mt) and EF-Ts(mt) are expressed differently in various tissues. Their expression in heart and liver increased during development and reached plateau at maturation. Expression of EF-Tu(mt) and EF-Ts(mt) exhi-bited similar tissue-specificity and changed synchronically during development. These results suggest that expression levels of EF-Tu(mt) and EF-Ts(mt) may be regulated by a similar mechanism related to the metabolic state of the cells.

Journal Article↗