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Biomedical subjects

X Chen

Publications and source records attributed to X Chen.

At least 163 records · Page 9Linked to original sources
PubMed2001

[Comparison of (1)H MRS, PET and EEG in lateralization of temporal lobe epilepsy].

OBJECTIVE: To evaluate and compare the role of (1)H MRS, PET and EEG in lateralization diagnosis (LD) of temporal lobe epilepsy (TLE). METHODS: 15 patients with intractable TLE verified by operation and pathology were studied. Before unilateral anterior temporal lobectomy, (1)H MRS, PET and EEG were performed for the LD of TLE. The diagnostic value of (1)H MRS, PET and EEG was compared based on the pathology and follow-up results. RESULTS: With video scalp EEG monitoring, the focus was localized in one temporal lobe for 13 patients among which 5 had abnormal waves conducted to the contralateral lobe. Intracranial EEG was performed for other 2 patients because scalp EEG failed to make the LD. Ultimately, partial temporal lobectomy was performed in all patients based on LD by scalp EEG or intracranial EEG. The pathological findings of operation specimens showed various degree of hippocampal sclerosis. The surgery was proved to be effective by follow-ups of all 15 patients, with their conditions controlled in 12 cases and better in two. EEG succeeded to make correct LD in all cases. (1)H MRS made correct LD in 12 cases (80%) and incorrect LD in 1 case, and failed to made LD in 2 cases. Five bilateral abnormalities (33%) were found by MRS. FDG-PET made correct LD in 14 cases (93%) and incorrect LD in 1 case, and found two cases with bilateral abnormalities (13%). CONCLUSION: (1)H MRS, PET and EEG are all effective means in LD of TLE. Up to now, scalp EEG is the first choice and continuous video EEG monitoring has its own unique advantage. As a kind of simple, noninvasive and objective method, MRS can be used as a routine examination in conjunction with conventional MRI. Although PET is quite sensitive, it is expensive and has a number of limitations. So it can be used depending on the affordability of patients or diagnostic need. Combination of MRI, MRS, PET and scalp EEG may improve the reliability of the LD compared with use of any one of them alone. While the results of these methods are controversial, intracranial EEG is inevitable.

Adolescent↗
PubMed2001

Towards a full karyotype screening of interphase cells: 'FISH and chip' technology.

Numerical chromosome aberrations are incompatible with normal human development. Our laboratories develop hybridization-based screening tools that generate a maximum of cytogenetic information for each polar body or blastomere analyzed. The methods are developed considering that the abnormality might require preparation of case-specific probes and that only one or two cells will be available for diagnosis, most of which might be in the interphase stage. Furthermore, assay efficiencies have to be high, since there is typically not enough time to repeat an experiment or reconfirm a result prior to fertilization or embryo transfer. Structural alterations are delineated with breakpoint-spanning probes. When screening for numerical abnormalities, we apply a Spectral Imaging-based approach to simultaneously score as many as ten different chromosome types in individual interphase cells. Finally, DNA micro-arrays are under development to score all of the human chromosomes in a single experiment and to increase the resolution with which micro-deletions can be delineated.

Blastomeres↗
PubMed2001

UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation.

Cul-4A, which encodes a member of the cullin family subunit of ubiquitin-protein ligases, is expressed at abnormally high levels in many tumor cells. CUL-4A can physically associate with the damaged DNA-binding protein (DDB), which is composed of two subunits, p125 and p48. DDB binds specifically to UV-damaged DNA and is believed to play a role in DNA repair. We report here that CUL-4A stimulates degradation of p48 through the ubiquitin-proteasome pathway, resulting in an overall decrease in UV-damaged DNA binding activity. The R273H mutant of p48 identified from a xeroderma pigmentosium (group E) patient is not subjected to CUL-4A-mediated proteolysis, consistent with its inability to bind CUL-4A. p125 is also an unstable protein, and its ubiquitination is stimulated by CUL-4A. However, the abundance of p125 is not dramatically altered by Cul-4A overexpression. UV irradiation inhibits p125 degradation, which is temporally coupled to the UV-induced translocation of p125 from the cytoplasm into the nucleus. CUL-4A is localized primarily in the cytoplasm. These findings identify DDB subunits as the first substrates of the CUL-4A ubiquitination machinery and suggest that abnormal expression of Cul-4A results in reduced p48 levels, thus impairing the ability of DDB in lesion recognition and DNA repair in tumor cells.

Animals↗
PubMed2001

Peptide mass mapping constrained with stable isotope-tagged peptides for identification of protein mixtures.

Through proteolysis and peptide mass determination using mass spectrometry, a peptide mass map (PMM) can be generated for protein identification. However, insufficient peptide mass accuracy and protein sequence coverage limit the potential of the PMM approach for high-throughput, large-scale analysis of proteins. In our novel approach, nonlabile protons in particular amino acid residues were replaced with deuteriums to mass-tag proteins of the S. cerevisiae proteome in a sequence-specific manner. The resulting mass-tagged proteolytic peptides with characteristic mass-split patterns can be identified in the data search using constraints of both amino acid composition and mass-to-charge ratio. More importantly, the mass-tagged peptides can further act as internal calibrants with high confidence in a PMM to identify the parent proteins at modest mass accuracy and low sequence coverage. As a result, the specificity and accuracy of a PMM was greatly enhanced without the need for peptide sequencing or instrumental improvements to obtain increased mass accuracy. The power of PMM has been extended to the unambiguous identification of multiple proteins in a 1D SDS gel band including the identification of a membrane protein.

Amino Acid Sequence↗
PubMed2001

Species-specific differences in the operational RNA code for aminoacylation of tRNA(Trp).

Identity elements play essential roles in the recognition of tRNAs by their cognate aminoacyl-tRNA synthetase. An operational RNA code relates amino acids to specific sequences and structural features of tRNA acceptor stems. In this study, a series of tRNA(Trp) variants was prepared by in vitro transcription and their efficiencies of aminoacylation by tryptophan (k(cat)/K(m)) were measured with the aid of Bacillus subtilis and human tryptophanyl-tRNA synthetases (TrpRS). The identity elements in the operational RNA code of human tRNA(Trp) were found to be: major element, discriminator base A73; minor elements, G1/C72 and U5/G68. From the cross-species aminoacylation assays, we conclude that the identity elements in tRNA(Trp) from B.subtilis and human all contribute to species-specific aminoacylation by TrpRS. Analyses of 22 TrpRS sequences covering three taxonomic domains (bacteria, eukarya and archaea) reveal that the sequences are divided into two evolutionarily distant groups. The same partition is also observed in the analyses of tRNA(Trp) acceptor stem sequences. Our data suggest that the two TrpRS groups may reflect co-adaptations needed to accommodate changes in the operational RNA code for tryptophan.

Acylation↗
PubMed2001

Receptor tyrosine kinase EphA2 is regulated by p53-family proteins and induces apoptosis.

The p53 tumor suppressor protein is mutated in more than 50% of all human cancers, which makes the study of its functions and activities critical for the understanding and management of cancer. In response to cellular stresses, p53 is activated and can mediate cell cycle arrest and/or apoptosis via the upregulation of numerous target genes. Here, we have identified EphA2 as a target gene of the p53 family, that is, p53, p73, and p63. We also found that an increase of EphA2 transcript levels correlated with an increase of EphA2 protein expression, and induction of EphA2 in response to DNA damage corresponded with p53 activation. Furthermore, we identified a p53 response element located within the EphA2 promoter that is responsive to wild-type p53, p73, and p63, but not mutant p53. Interestingly, the ligand for EphA2, ephrin-A1, is also regulated by p53. EphA2 and ephrin-A1 are members of the Eph family of receptor tyrosine kinases and ligands, which are implicated in a number of developmental processes. To analyse the role of EphA2 in p53-mediated tumor suppression, we generated stable cell lines capable of expressing exogenous EphA2 in a tetracycline-repressible system. We found that EphA2 expression resulted in an increase in apoptosis. Thus, we hypothesize that the activated EphA2 may serve to impair anti-apoptotic signaling, perhaps by disrupting focal adhesions and thereby sensitize cells to pro-apoptotic stimuli.

Apoptosis↗
PubMed2001

Continuum description of rarefied gas dynamics. I. Derivation from kinetic theory.

We describe an asymptotic procedure for deriving continuum equations from the kinetic theory of a simple gas. As in the works of Hilbert, of Chapman, and of Enskog, we expand in the mean flight time of the constituent particles of the gas, but we do not adopt the Chapman-Enskog device of simplifying the formulas at each order by using results from previous orders. In this way, we are able to derive a new set of fluid dynamical equations from kinetic theory, as we illustrate here for the relaxation model for monatomic gases. We obtain a stress tensor that contains a dynamical pressure term (or bulk viscosity) that is process dependent and our heat current depends on the gradients of both temperature and density. On account of these features, the equations apply to a greater range of Knudsen number (the ratio of mean free path to macroscopic scale) than do the Navier-Stokes equations, as we see in the accompanying paper. In the limit of vanishing Knudsen number, our equations reduce to the usual Navier-Stokes equations with no bulk viscosity.

Journal Article↗
PubMed2001

[The significance of Titin antibody in diagnosing myasthenia gravis with thymoma].

OBJECTIVE: To investigate the clinical significance of Titin antibody (Titin-ab) in diagnosing myasthenia gravis with thymoma (MGT). METHODS: Titin-ab and acetylcholine receptor antibody (AChR-ab) in the sera of 73 MGT patients with different thymic pathological patterns and 58 MG patients without thymoma (NTMG) were detected by ELISA. RESULTS: The positive rate of Titin-ab in MGT group was 76.7%, significantly higher than those of NTMG group, other neurologic diseases group and healthy control group (P < 0.01). The sensitivity of Titin-ab in diagnosis of MGT was significantly lower than that of CT scan or MR of thymus (P < 0.05), but the specificity of Titin-ab in diagnosis of MGT was significantly higher than that of CT scan or MR of thymus (P < 0.05). The positive rate of Titin-ab was mainly related to the thymic pathology and was the highest in the thymic epithelial thymoma (TET) subgroup (95.1%). There was no significant correlation between the positive rate of Titin-ab and the Masaoka's stage of thymoma (P > 0.05). The titer of Titin-ab was highly correlated to the titer of AChR-ab in MGT group (r = 0.496, P < 0.01), but not in MGH group (r = 0.385, P > 0.05). CONCLUSION: Detection of Titin-ab is a rather sensitive, specific, handy method in diagnosis of MGT (especially TET). It may play an important role in the pathogenesis of MGT.

Adolescent↗
PubMed2001

Global stability, local stability and permanence in model food webs.

The dynamical theory of food webs has been based typically on local stability analysis. The relevance of local stability to food web properties has been questioned because local stability holds only in the immediate vicinity of the equilibrium and provides no information about the size of the basin of attraction. Local stability does not guarantee persistence of food webs in stochastic environments. Moreover, local stability excludes more complex dynamics such as periodic and chaotic behaviors, which may allow persistence. Global stability and permanence could be better criteria of community persistence. Our simulation analysis suggests that these three stability measures are qualitatively consistent in that all three predict decreasing stability with increasing complexity. Some new predictions on how stability depends on food web configurations are generated here: a consumer-victim link has a smaller effect on the probabilities of stability, as measured by all three stability criteria, than a pair of recipient-controlled and donor-controlled links; a recipient-controlled link has a larger effect on the probabilities of local stability and permanence than a donor-controlled link, while they have the same effect on the probability of global stability; food webs with equal proportions of donor-controlled and recipient-controlled links are less stable than those with different proportions.

Animals↗
PubMed2001

Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer.

TRAIL/Apo-2L is a member of the tumor necrosis factor superfamily and has recently been shown to induce apoptosis in cancer cells, but not in normal cells. In nude mice injected with human tumors, TRAIL reduces the size of these tumors without side effects. Akt promotes cell survival and block apoptosis. Some prostate cancer cells express high levels of Akt due to lack of active lipid phosphatase PTEN, a negative regulator of PI-3 kinase pathway, which may be responsible for drug resistance. The objective of this paper is to investigate the intracellular molecules that regulate TRAIL resistance. We have examined caspase-8 activity, BID cleavage, Akt activity, mitochondrial membrane potential (DeltaPsi(m)) and apoptosis in prostate cancer (LNCap, PC-3, PC-3M and DU145) cells treated with or without TRAIL. PC-3, PC-3M and DU145 cells are sensitive to TRAIL, whereas LNCap cells are resistant. LNCap cells express the highest level of constitutively active Akt, which is directly correlated with TRAIL resistance. TRAIL activates caspase-8 in all the cell lines. Downregulation of constitutively active Akt by PI-3 kinase inhibitors (wortmannin and LY-294002), dominant negative Akt or PTEN, renders LNCap cells sensitive to TRAIL. Inhibition of TRAIL sensitivity occurs at the level of BID cleavage. Inhibition of protein synthesis by cycloheximide also causes LNCap cells sensitive to TRAIL. Overexpression of Bcl-2 or Bcl-X(L) inhibits TRAIL-induced DeltaPsi(m) and apoptosis. Overexpression of constitutively active Akt in PC-3M cells (express very low levels of constitutively active Akt) restores TRAIL resistance. These data suggest that elevated Akt activity protects LNCap cells from TRAIL-induced apoptosis, and the PI-3 kinase/Akt pathway may inhibit apoptotic signals by inhibiting processing of BID. Thus, constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer.

Androstadienes↗
PubMed2001

Maternal glucose concentration influences fetal growth, gestation, and pregnancy complications.

Using 1990-1995 data, the authors examined the influence of post-challenge maternal glucose concentration on pregnancy outcome in 1,157 nondiabetic US gravidas. After control for potential confounding variables and comparing gravidas with lower glucose concentrations (<99 mg/dl) with the others, they found that mean birth weight increased by 50 g and 200 g with glucose concentrations of 99-130 mg/dl and >130 mg/dl, respectively. Increased maternal glucose concentration also was associated with an increased risk of large-for-gestation fetuses (p for trend < 0.001) and a decreased risk of fetal growth restriction (p for trend < 0.05). The association between glucose and gestation was inverse and significantly shortened when glucose concentrations were higher. Maternal complications increased twofold or more with high glucose concentrations and included cesarean section and clinical chorioamnionitis. Chorioamnionitis in combination with high maternal glucose concentration increased the risk of very preterm delivery almost 12-fold. These observations extend Pedersen's hypothesis-that high concentrations of maternal glucose give rise to increased nutrient transfer to the fetus and increase fetal growth, beyond the model of maternal diabetes (Acta Endocrinol 1954;16:330-42). They raise the question of whether higher, but seemingly normal maternal glucose concentration predisposes to or is a marker for placental inflammation and infection.

Adolescent↗
PubMed2001

Li2AlB5O10.

A new compound, dilithium aluminium pentaborate, Li(2)AlB(5)O(10), has been synthesized by solid-state reaction and its structure determined by single-crystal X-ray diffraction. This compound is composed of [B(5)O(10)](5-) groups linked by AlO(4) tetrahedra. The [B(5)O(10)](5-) group consists of two hexagonal B-O rings perpendicular to each other connected by tetracoordinated boron. All the B-O rings in this structure can be divided into two groups, with one group approximately parallel and the other perpendicular to the c axis.

Journal Article↗
PubMed2001

[The change of human Na+/dicarboxylate co-transporter 1 expression in the kidney and its relationship with pathogenesis of nephrolithiasis].

OBJECTIVE: To study the change of Na+/dicarboxylate co-transporter 1 expression in the kidney and its relationship with nephrolithiasis. METHODS: 50 volunteers and 85 patients with nephrolithiasis were divided into 3 groups: control, nephrolithiasis with normal urine citrate, and nephrolithiasis with hypocitraturia. The expression of hNaDC1 mRNA in kidney was determined by RT-PCR or Northern blotting, the change of hNaDC1 protein abundance were measured by immunohistochemical staining with anti-hNaDC1 antibody among part of these patients and volunteers. The plasma and urinary biochemical parameters, such as citrate, oxalate, uric acid and calcium etc., were analyzed by routine chemical methods. RESULTS: The recurrence rate of nephrolithiasis in the group of patients with hypocitraturia was 36.1%, significantly higher than the recurrence rate of 16.3% in the group of patients with normal urine citrate (P < 0.01). hNaDC1 was expressed in the normal kidney, localized in the striated border of renal proximal tubule. However, it was expressed highly in the kidneys of patients with hypocitraturia. The ratio hNaDC1 mRNA/18sRNA in the patients with hypocitraturia was 0.65 +/- 0.21, significantly higher than that in the controls (0.36 +/- 0.11, P < 0.01). The ratio hNaDC1 mRNA/18sRNA in the patients with normal urine citrate was not significantly different from that in the controls (P > 0.05). The urine pH and urine sodium were significantly lower in the patients with hypocitraturia than in the other two groups. The levels of urine calcium and urine oxalate were significantly higher in the patients with hypocitraturia than in the controls, and were not different from those in the patients with normal urine citrate. CONCLUSION: The upregulation of hNaDC1 mRNA and protein abundance in the kidney may be an important cause of hypocitraturia, which might be related with the occurrence and recurrence of nephrolithiasis.

Adult↗
PubMed2001

Fluorophore-labeled S-nitrosothiols.

A series of fluorophore-labeled S-nitrosothiols were synthesized, and their fluorescence enhancements upon removal of the nitroso (NO) group were evaluated either by transnitrosation or by photolysis. It was shown that, with a suitable alkyl linker, the fluorescence intensity of dansyl-labeled S-nitrosothiols could be enhanced up to 30-fold. The observed fluorescence enhancement was attributed to the intramolecular energy transfer from fluorophore to the SNO moiety. Ab initio density functional theory (DFT) calculations indicated that the "overlap" between the SNO moiety and the dansyl ring is favored because of their stabilizing interaction, which was in turn affected by both the length of the alkyl linker and the rigidity of the sulfonamide unit. In addition, one of the dansyl-labeled S-nitrosothiols was used to explore the kinetics of S-nitrosothiol/thiol transnitrosation and was evaluated as a fluorescence probe of S-nitrosothiol-bound NO transfer in human umbilical vein endothelial cells.

Cell Membrane↗
PubMed2001

N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors.

Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H(2)O(2). These compounds also displayed vasodilatory activity.

Animals↗
PubMed2001

Separation and determination of podophyllum lignans by micellar electrokinetic chromatography.

A micellar electrokinetic chromatography method was established for the quantitative analysis of seven podophyllum lignans in Podophyllum emodi Wall. var. chinesis sprague. The optimum buffer system was 10 mM NaH2PO4-5 mM borate-100 mM sodium dodecylsulfate-30% isopropanol (pH 7.20). Voltage was 18 kV and detection at 214 nm. The second derivative chromatogram was used to determine a low-content component and those not fully separated from adjacent ones. The RSD values of migration times and peak areas were <2.2 and <5.5%, respectively. The effects of several CE parameters on the resolutions were studied systematically.

Chromatography, Micellar Electrokinetic Capillary↗