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Biomedical subjects

X M Li

Publications and source records attributed to X M Li.

At least 55 records · Page 3Linked to original sources
PubMed2000

Substantia nigra pars reticulata lesion induces preconvulsive behavior and changes in glutamate receptor gene expression in the rat brain.

The substantia nigra pars reticulata (SNpr) has been proposed to play an important role in the control of the propagation and/or the generation of epileptic seizures. Earlier studies have shown differential effects of the lesion of the SNpr on seizure genesis that demonstrated a regional difference in the anterior and posterior parts of the SNpr in preconvulsive behavior induced by unilateral reticulata injection of dopamine (DA). This study was aimed to investigate some of the underlying mechanisms of the preconvulsive behavior elicited by unilateral SNpr DA injection by the study of changes in the gene expression of glutamate receptor subunits (GluR1, GluR2 and NMDAR1) and of changes in animal behavior following coinfusion of DA and a DA D1 antagonist SCH 23390 into the SNpr. Unilateral injection of exogenous DA into the anterior region of the SNpr induced rapid and short lasting preconvulsive behavior up to wet dog shakes stage and a significant reduction of gene expression for GluR1, GluR2 and NMDAR1 subunits in rat hippocampal subfields including CA1 through CA4 and dentate gyrus (DG) at 1 day after nigral DA injection. The effect was long lasting and persisted for at least 3 weeks. Both preconvulsive behavior and downregulation of glutamate receptor subunit genes were completely blocked by simultaneous coinfusion of DA and SCH 23390. The results suggest, for the first time, that DA D1 receptor in the SNpr may mediate the nigral-involved seizure development. Glutamate desensitization, and/or selective early neuronal damage might be responsible for the downregulation of glutamate receptor subunits by transient preconvulsive activity.

Animals↗
PubMed2000

Intracellular modulation of NMDA receptor function by antipsychotic drugs.

The present study deals with the functional interaction of antipsychotic drugs and NMDA receptors. We show that both the conventional antipsychotic drug haloperidol and the atypical antipsychotic drug clozapine mediate gene expression via intracellular regulation of NMDA receptors, albeit to different extents. Data obtained in primary striatal culture demonstrate that the intraneuronal signal transduction pathway activated by haloperidol, the cAMP pathway, leads to phosphorylation of the NR1 subtype of the NMDA receptor at (897)Ser. Haloperidol treatment is likewise shown to increase (897)Ser-NR1 phosphorylation in rats in vivo. Mutation of (896)Ser and (897)Ser to alanine, which prevents phosphorylation at both sites, inhibits cAMP-mediated gene expression. We conclude that antipsychotic drugs have the ability to modulate NMDA receptor function by an intraneuronal signal transduction mechanism. This facilitation of NMDA activity is necessary for antipsychotic drug-mediated gene expression and may contribute to the therapeutic benefits as well as side effects of antipsychotic drug treatment.

Animals↗
PubMed2000

Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases.

We have imaged, in real time, fluorescent tumors growing and metastasizing in live mice. The whole-body optical imaging system is external and noninvasive. It affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals. We have established new human and rodent tumors that stably express very high levels of the Aequorea victoria green fluorescent protein (GFP) and transplanted these to appropriate animals. B16F0-GFP mouse melanoma cells were injected into the tail vein or portal vein of 6-week-old C57BL/6 and nude mice. Whole-body optical images showed metastatic lesions in the brain, liver, and bone of B16F0-GFP that were used for real time, quantitative measurement of tumor growth in each of these organs. The AC3488-GFP human colon cancer was surgically implanted orthotopically into nude mice. Whole-body optical images showed, in real time, growth of the primary colon tumor and its metastatic lesions in the liver and skeleton. Imaging was with either a trans-illuminated epifluorescence microscope or a fluorescence light box and thermoelectrically cooled color charge-coupled device camera. The depth to which metastasis and micrometastasis could be imaged depended on their size. A 60-microm diameter tumor was detectable at a depth of 0.5 mm whereas a 1, 800-microm tumor could be visualized at 2.2-mm depth. The simple, noninvasive, and highly selective imaging of growing tumors, made possible by strong GFP fluorescence, enables the detailed imaging of tumor growth and metastasis formation. This should facilitate studies of modulators of cancer growth including inhibition by potential chemotherapeutic agents.

Adenocarcinoma↗
PubMed2000

Expression of platelet-derived endothelial cell growth factor and vascular endothelial growth factor in hepatocellular carcinoma and portal vein tumor thrombus.

PURPOSE: Both platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) are known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We aimed at evaluating the gene expression of PD-ECGF and VEGF in hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS: Surgical specimens (28 HCC, 28 nontumorous liver tissues and 18 PVTT) were studied by Northern blot analysis. The levels of PD-ECGF mRNA and VEGF mRNA expression were measured by densitometric scanning of the autoradiographs, and they were normalized to the level of expression of an internal control (glyceraldehydephosphate dehydrogenase) mRNA. RESULTS: The expression rates of PD-ECGF mRNA in PVTT, HCC and nontumorous liver tissues were 77.8% (14/18), 67.9% (19/28) and 35.7% (10/28), being 88.9% (16/18), 75.0% (21/28) and 17.9% (5/28) respectively for VEGF mRNA. The expressions of PD-ECGF mRNA and VEGF mRNA were higher in HCC with PVTT than when PVTT was absent (P < 0.05). The PVTT was more often seen in patients with positive expression of both PD-ECGF mRNA and VEGF mRNA in HCC than in patients who were positive for only one of these factors or negative for both (P < 0.05). CONCLUSION: Both PD-ECGF and VEGF correlated well with the formation of PVTT of HCC.

Adult↗
PubMed2000

Sphingomyelin interfacial behavior: the impact of changing acyl chain composition.

Sphingomyelins (SMs) containing homogeneous acyl chains with 12, 14, 16, 18, 24, or 26 carbons were synthesized and characterized using an automated Langmuir-type film balance. Surface pressure was monitored as a function of lipid molecular area at constant temperatures between 10 degrees C and 30 degrees C. SM containing lauroyl (12:0) acyl chains displayed only liquid-expanded behavior. Increasing the length of the saturated acyl chain (e.g., 14:0, 16:0, or 18:0) resulted in liquid-expanded to condensed two-dimensional phase transitions at many temperatures in the 10-30 degrees C range. Similar behavior was observed for SMs with lignoceroyl (24:0) or (cerotoyl) 26:0 acyl chains, but isotherms showed only condensed behavior at 10 and 15 degrees C. Insights into the physico-mechanical in-plane interactions occurring within the different SM phases and accompanying changes in SM phase state were provided by analyzing the interfacial area compressibility moduli. At similar surface pressures, SM fluid phases were less compressible than those of phosphatidylcholines with similar chain structures. The area per molecule and compressibility of SM condensed phases depended upon the length of the saturated acyl chain and upon spreading temperature. Spreading of SMs with very long saturated acyl chains at temperatures 30-35 degrees below T(m) resulted in condensed films with lower in-plane compressibilities, but consistently larger cross-sectional molecular areas than the condensed phases achieved by spreading at temperatures only 10-20 degrees below T(m). This behavior is discussed in terms of the enhancement of SM lateral aggregation by temperature reduction, a common approach used during domain isolation from biomembranes.

Biophysical Phenomena↗
PubMed2000

Recurrent chromosome changes in 62 primary gastric carcinomas detected by comparative genomic hybridization.

Comparative genomic hybridization (CGH) has been applied to detect recurrent chromosome alterations in 62 primary gastric carcinomas. Several nonrandom chromosomal changes, including gains of 8q (31 cases, 50%), 20q (29 cases, 47%) with a minimum gain region at 20q11. 2-q12, 13q (21 cases, 34%) with a minimum gain region at 13q22, and 3q (19 cases, 31%) were commonly observed. The regions most frequently lost included: 19p (23 cases, 37%), 17p (21 cases, 33%), and 1p (14 cases, 23%). High copy number gain (DNA sequence amplification) was detected in 6 cases. Amplification of 8q23-q24.2 and 20q11.2-q12 were observed in 3 cases. Gain of 20q and loss of 19p were confirmed by fluorescence in situ hybridization using corresponding bacterial artificial chromosomes (BAC) clones from those regions. The gain and loss of chromosomal regions identified in this study provide candidate regions involved in gastric tumorigenesis.

Adult↗
PubMed2000

The IAP family: endogenous caspase inhibitors with multiple biological activities.

IAPs (inhibitors of apoptosis) are a family of proteins containing one or more characteristic BIR domains. These proteins have multiple biological activities that include binding and inhibiting caspases, regulating cell cycle progression, and modulating receptor-mediated signal transduction. Our recent studies found the IAP family members XIAP and c-IAP1 are ubiquitinated and degraded in proteasomes in response to apoptotic stimuli in T cells, and their degradation appears to be important for T cells to commit to death. In addition to three BIR domains, each of these IAPs also contains a RING finger domain. We found this region confers ubiquitin protease ligase (E3) activity to IAPs, and is responsible for the auto-ubiquitination and degradation of IAPs after an apoptotic stimulus. Given the fact that IAPs can bind a variety of proteins, such as caspases and TRAFs, it will be of interest to characterize potential substrates of the E3 activity of IAPs and the effects of ubiquitination by IAPs on signal transduction, cell cycle, and apoptosis.

Animals↗
PubMed2000

A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses.

BACKGROUND: Peanut allergy affects 0.6% of the US population. At the present time, allergen avoidance is the only therapeutic option. Animal models of food-induced anaphylaxis would facilitate attempts to design novel immunotherapeutic strategies for the treatment of peanut allergy. OBJECTIVE: The purpose of this study was to develop a murine model of IgE-mediated peanut hypersensitivity that closely mimics human peanut allergy. METHODS: C3H/HeJ mice sensitized orally with freshly ground whole peanut and cholera toxin as adjuvant were challenged orally 3 and 5 weeks later with crude peanut extract. Anaphylactic reactions were determined. T- and B-cell responses to Ara h 1 and Ara h 2, the major peanut allergens, were characterized by evaluating splenocyte proliferative responses and IgE antibody concentrations. Furthermore, IgE antibodies in the sera of patients with peanut allergy and mice were compared for antibody binding to Ara h 2 isoforms and allergenic epitopes. RESULTS: Peanut-specific IgE was induced by oral peanut sensitization, and hypersensitivity reactions were provoked by feeding peanut to sensitized mice. The symptoms were similar to those seen in human subjects. Ara h 1- and Ara h 2-specific antibodies were present in the sera of mice with peanut allergy. Furthermore, these Ara h 2-specific IgE antibodies bound the same Ara h 2 isoforms and major allergenic epitopes as antibodies in the sera of human subjects with peanut allergy. Splenocytes from mice with peanut allergy exhibited proliferative responses to Ara h 1 and Ara h 2. CONCLUSION: This murine model of peanut allergy mimics the clinical and immunologic characteristics of peanut allergy in human subjects and should be a useful tool for developing immunotherapeutic approaches for the treatment of peanut allergy.

2S Albumins, Plant↗
PubMed2000

The chinese herbal medicine formula MSSM-002 suppresses allergic airway hyperreactivity and modulates TH1/TH2 responses in a murine model of allergic asthma.

BACKGROUND: Asthma is a major public health problem worldwide, and the morbidity and mortality of asthma have increased in the past two decades. The reputed efficacy, low cost, and relative absence of side effects of traditional Chinese medicines (TCMs) have led to increasing interest in the use of TCMs for the treatment of asthma in Western countries. However, there are few well-controlled scientific studies on the efficacy, safety, and mechanisms of action of TCMs used to treat asthma. OBJECTIVE: The goal of this study was to investigate the effects of the Chinese herbal medicine formula MSSM-002, derived from TCMs used to treat allergic asthma, on a well-characterized mouse model of allergic asthma. METHODS: Mice sensitized intraperitoneally and challenged intratracheally with conalbumin were treated with MSSM-002 24 hours after the first intratracheal challenge. Dexamethasone-treated, saline solution sham-treated, and naive mice served as controls. The effects of MSSM-002 on allergic airway hyperreactivity, inflammation, antigen-specific antibody production, lung histologic features, and cytokine profiles were evaluated. RESULTS: MSSM-002 treatment virtually eliminated airway hyperreactivity and markedly reduced the total number of cells and the percent eosinophils in bronchoalveolar lavage fluids compared with the sham-treated group. Lung histologic features showed that MSSM-002 reduced inflammation and mucus production. These effects were equivalent to the effects of dexamethasone, but in contrast to the overall immunosuppressive effects of dexamethasone MSSM-002 treatment decreased antigen-specific IgE, IL-4, IL-5, and IL-13 levels without suppressing IgG2a and IFN-gamma synthesis. CONCLUSION: MSSM-002 exhibits anti-airway hyperresponsiveness, anti-airway inflammation, and immunoregulatory effects on T(H)1/T(H)2 responses, which may be useful for treatment of allergic asthma.

Animals↗
PubMed2000

Developmental control of stress stimulons in Streptomyces coelicolor revealed by statistical analyses of global gene expression patterns.

Stress-induced regulatory networks coordinated with a procaryotic developmental program were revealed by two-dimensional gel analyses of global gene expression. Four developmental stages were identified by their distinctive protein synthesis patterns using principal component analysis. Statistical analyses focused on five stress stimulons (induced by heat, cold, salt, ethanol, or antibiotic shock) and their synthesis during development. Unlike other bacteria, for which various stresses induce expression of similar sets of protein spots, in Streptomyces coelicolor heat, salt, and ethanol stimulons were composed of independent sets of proteins. This suggested independent control by different physiological stress signals and their corresponding regulatory systems. These stress proteins were also under developmental control. Cluster analysis of stress protein synthesis profiles identified 10 different developmental patterns or "synexpression groups." Proteins induced by cold, heat, or salt shock were enriched in three developmental synexpression groups. In addition, certain proteins belonging to the heat and salt shock stimulons were coregulated during development. Thus, stress regulatory systems controlling these stimulons were implicated as integral parts of the developmental program. This correlation suggested that thermal shock and salt shock stress response regulatory systems either allow the cell to adapt to stresses associated with development or directly control the developmental program.

Bacterial Proteins↗
PubMed2000

Relationship of atypical melatonin rhythm with two circadian clock outputs in B6D2F(1) mice.

Circadian rhythms in body temperature, locomotor activity, and the circadian changes of plasma and pineal melatonin content were investigated in B6D2F(1) mice synchronized by 12 h of light and 12 h of darkness. During 8 wk continuous recording, activity and temperature displayed a marked stable and reproducible circadian rhythm, with both peaks occurring near the middle of darkness. Both 24- and 12-h rhythmic components were also significantly detected. Mean plasma melatonin concentration rose steadily during the light span and reached a maximum (30.6 +/- 10.0 pg/ml) at 11 h after light onset (HALO), then gradually decreased after the onset of darkness to a nadir (4.7 +/- 0.4 pg/ml) at 20 HALO. Mean pineal content followed a pattern parallel to that of plasma concentration (peak at 11 HALO: 17.7 +/- 1.0 pg/gland; trough at 17 HALO: 4.7 +/- 1.0 pg/gland). In addition, a second sharp peak was observed at 21 HALO (20.2 +/- 3.5 pg/gland). Plasma and pineal contents displayed large and statistically significant circadian changes, with a composite rhythm of period (24 + 12 h). This mouse model has predominant production and secretion of melatonin during the day. This possibly contributes to a similar coupling between chronopharmacology mechanisms and the rest-activity cycle in these mice and in human subjects.

Animals↗
PubMed2000

Antidepressants upregulate messenger RNA levels of the neuroprotective enzyme superoxide dismutase (SOD1).

OBJECTIVE: To investigate the effect of amitriptyline, bupropion, doxepin or venlafaxine on the gene expression of the neuroprotective enzyme superoxide dismutase (SOD1) in a catecholamine cell in vitro model. DESIGN: Molecular study of a cultured cell line. INTERVENTIONS: Rat pheochromocytoma (PC12) cells were incubated in 1 and 10 mumol/L of various antidepressant medications for 24 or 48 hours. OUTCOME MEASURES: Northern blot analysis. RESULTS: Amitriptyline up-regulated SOD1 messenger RNA in a time- and dose-dependent manner. The greatest up-regulation was following incubation with 10 mumol/L amitriptyline for 48 hours. The addition of bupropion, doxepin or venlafaxine to PC12 cell cultures also up-regulated SOD1 mRNA. CONCLUSIONS: These findings suggest that some antidepressants have the ability to positively regulate neuroprotective genes.

Amitriptyline↗
PubMed2000

[Prediction and evaluation of heterosis of beef cattle and their application].

The genetic structure and genetic variation of eight beef cattle cross parents populations were analyzed by six microsatellite loci, and heterosis of beef cattle was predicted. On the basis of microsatellite analysis, the effect of 18 cross combinations was estimated by the method of individual animal model BLUP. A new method of molecular quantitative genetics that select best of all cross combination was submitted. The results showed that the combinations with Hereford Limousine and Charolais as paternal parent are better than others in Fengning and Longhua regions; the combinations with Limousine Angus and Hereford as paternal parent are better than others in Zanhuang regions; the combinations with Hereford Limousine and Piemontese as paternal parent are better than others in Funing regions. Effect of three breeds cross is better than two breeds.

Animals↗
PubMed2000

[Kinetics for terephthalic acid anaerobic degradation with easily biodegradable organic material co-existence].

The fact of preferential substrate utilization results in a sequence of substrate attack. As typically, the easily biodegradable substrates in TA-containing wastewater are degraded firstly through methane fermentation pathway, and just those intermediate metabolites have been proved to be inhibitors for TA biodegradation. Moreover, TA itself can inhibit the TA biodegradation, too. A kinetic model for the anaerobic digestion of wastewater containing both TA and easily biodegradable pollutants is constructed as q = qmax [formula: see text], The model parameters are estimated with non-linear regression method, the values are as follows: qmax = 1972.0 mgTA/gVSS.d; Ks = 20.2844 gTA/L; Ki,i = 2.041 gCOD/L; Ki,s = 0.0108 gTA/L. The experimental data verification for the model equation is satisfactory. According to the model analysis, a new strategy, a two-step anaerobic system, dealing with this kind of wastewater is suggested.

Anaerobiosis↗
PubMed2000

Rapid assay of A1c-type glycosylated hemoglobin in blood of diabetic rats using fast protein liquid chromatography.

AIM: To develop a fast protein liquid chromatography (FPLC) method for the assay of Alc-type glycosylated hemoglobin in diabetic rats. METHODS: Venous blood was collected from rats. After the erythrocytes were washed and sedimented, the hemolysate was prepared and diluted with isotonic saline as a sample for the assay. Samples were then separated on Mono_S_HR_5/5 cation exchange column by a lithium chloride gradient elution system. The Alc-type glycosylated hemoglobin was monitored by measuring the absorbance at 415 nm. RESULTS: The Alc-type glycosylated hemoglobin was well separated from total hemoglobin. The average HbAlc amount in diabetic rats was determined to be (3.6% +/- 0.6%, n = 7), while the corresponding figure in normal rats was (1.4% +/- 0.4%, n = 7, P < 0.01). CONCLUSION: This FPLC method is easy, rapid and reproducible, and can be used for an assay of diabetic rat HbAlc to evaluate and screen new drugs for diabetes mellitus therapy.

Animals↗