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Biomedical subjects

W Jiang

Publications and source records attributed to W Jiang.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Relationship among telomerase activity, telomerase RNA and telomerase catalytic subunit gene expression and their significance in non small-cell lung cancer].

OBJECTIVE: To study telomerase activity (TA), telomerase RNA (hTR) and telomerase catalystic subunit (hTRT/hEST2) code gene expression in non-small cell lung cancer (NSCLC), their relationship and significance. METHODS: Telomerase repeat amplification protocol PCR (TRAP-PCR) for TA, RT-PCR for hTR and in situ hybridization for hTRT/hEST2 mRNA expression were performed. RESULTS: Positive rates of TA, hTR and hTRT/hEST2 were 68.4%(26/38), 51.7%(32/58) and 74.2%(43/58) in NSCLC. But, the adjacent and benign lung tissues were negative for expression of TA, hTR and hTRT/hEST2. A statistically significant positive correlation between TA and hTRT/hEST2 was observed(r = 0.84, P = 0.01), though there was no statistically significant positive association between TA and hTR (r = 0.16, P = 0.23). The median survivals of TA and hTRT/hEST2 positive groups (10.4 months, 7.5 months) were shorter than the negative ones (13.5 months, 14.7 months). However, only the hTRT/hEST2 group was found to show statistical significance to be an independent prognostic factor by multivariate Cox regression analysis. CONCLUSION: Telomerase activity, hTR expression and hTRT/hEST2 are frequently detected at higher levels in NSCLC than the pericancerous normal tissues. There is a positive correlation between TA and hTRT/hEST2, both of which are markers of poor magnificent phenotype of NSCLC. The hTRT/hEST2 has an independent prognostic significance.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

[Quantitative detection of flow indices in tubal flow via pulsed Doppler ultrasound, in vitro].

OBJECTIVE: This paper deals with the method and feasibility of quantitative detection of flow indices via commercially available Pulsed Doppler Ultrasound. METHODS: The indices, such as Reynolds number, relative spectral broadening (RSB), laminar shear stress and Reynolds normal stress (RNS) were selected and evaluated. Detection was done temporally and spatially, upstream and downstream of the stenosis. The data were evaluated qualitatively and quantitatively. RESULTS: The roughest turbulence was met at 1/2R sample volume, 1.0 cm downstream of the stenosis. CONCLUSION: The methodology in this study is proved to be feasible and may have good prospects in clinical use.

Biomechanical Phenomena↗
PubMed2001

[The influences upon the passive tensile of the masticatory muscles and ligaments by Herbst appliance under various bite reconstruction--a three dimensional finite element analysis].

OBJECTIVE: This study aimed to provide some biomechanical references for the clinical use and improvement of Herbst appliance. METHODS: The three-dimensional model of the 'Temporomandibular joint mandible Herbst appliance system' was set up by SUPER SAP software (version 9.3). On this model, the passive tensile in the masticatory muscles and ligaments were analyzed under various bit reconstruction designed according to specified advanced displacement and vertical bite opening. RESULTS: When Herbst appliance drove the mandible forward, there was not any tensile in the medial, lateral pterygoid and the collateral ligament, while the temporalis, the deep paret of masseter, the stylomandibular ligament, and the sphenomandibular ligament were passively drawn. Under various bite reconstruction, the passive tensile in the medial temporalis, the posterior temporalis, the stylomandibular ligament and the sphenomandibular ligament increased with the amount of the advancement of the mandible; The passive tensile in the posterior temporalis and the deep part of masseter increased with the amount of vertical bite opening of the mandible. CONCLUSION: The StL, SpL, PT and AT played an important role in functional reconstruction of mandible by Herbst. All five group of bite reconstruction (3-7 mm advancement, 4-2 mm vertical bite opening of the mandible) designed by this study can be selected in clinic according to the patient's capability of adaptation, the extent of malocclusion and the potential and direction of growth.

Finite Element Analysis↗
PubMed2001

[The influences of the stress distribution on the condylar cartilage surface by Herbst appliance under various bite reconstruction--a three dimensional finite element analysis].

OBJECTIVE: The distribution of stress on the surface of condylar cartilage was investigated. METHODS: Three-dimensional model of the 'Temporomandibular joint mandible Herbst appliance system' was set up by SUPER SAP software (version 9.3). On this model, various bite reconstruction was simulated according to specified advanced displacement and vertical bite opening. The distribution of maximum and minimum principal stress on the surface of condylar cartilage were computerized and analyzed. RESULTS: When Herbst appliance drove the mandible forward, the anterior condyle surface was compressed while the posterior surface was drawn. The trend of stress on the same point on the condyle surface was consistent in various reconstruction conditions, but the trend of stress on various point were different in same reconstruction conditions. CONCLUSION: All five groups of bite reconstruction (3-7 mm advancement, 4-2 mm vertical bite opening of the mandible) designed by this study can be selected in clinic according to the patient's capability of adaptation, the extent of malocclusion and the potential and direction of growth.

Cartilage, Articular↗
PubMed2001

[The clinical significance of detection of urinary ceruloplasmin in type 2 diabetes].

OBJECTIVE: To evaluate the clinical significance of detection of urinary ceruloplasmin (Cp) in type 2 diabetes. METHODS: To measure albumin/creatinine(Alb/Cr) and Cp/Cr in morning urinary specimens, from 134 normal controls and 3 960 diabetes, with RIA and ELISA separately. RESULTS: (1) The range of urinary Cp/Cr for normal controls was 0.01 - 1.12 ng/mmol, median 0.36 ng/mmol. Cp/Cr > 0.924 ng/mmol was considered as abnormal, and there was no significant difference between males and females, as well as among subjects of different age. (2) The sensitivity and specificity of Cp/Cr were 90% and 66% respectively with Alb/Cr > 2.5 mg/mmol as a golden standard for diabetic nephropathy, and Kappa value 0.48. Urinary Cp/Cr correlated well with Alb/Cr. (3)After sub-maximal exercise, Cp/Cr elevated markedly with no significant change of Alb/Cr. CONCLUSION: Urinary Cp/Cr could be considered as a marker of diabetic nephropathy and might be more sensitive than Alb/Cr.

Adult↗
PubMed2000

Transcriptional analysis of chromatin assembled with purified ACF and dNAP1 reveals that acetyl-CoA is required for preinitiation complex assembly.

To investigate the role of chromatin structure in the regulation of transcription by RNA polymerase II, we developed a chromatin transcription system in which periodic nucleosome arrays are assembled with purified recombinant ATP-utilizing chromatin assembly and remodeling factor (ACF), purified recombinant nucleosome assembly protein 1 (dNAP1), purified native core histones, plasmid DNA, and ATP. With this chromatin, we observed robust activation of transcription with three different transcription factor sets (nuclear factor kappaB p65 + Sp1, estrogen receptor, and Gal4-VP16) added either before or after chromatin assembly. In fact, the efficiency of activated transcription from the ACF + dNAP1-assembled chromatin was observed to be comparable with that from naked DNA templates or chromatin assembled with a crude Drosophila extract (S190). With ACF + dNAP1-assembled chromatin, we found that transcriptional activation is dependent upon acetyl-CoA. This effect was not seen with naked DNA templates or with crude S190-assembled chromatin. We further determined that acetyl-CoA is required at the time of preinitiation complex assembly but not during assembly of the chromatin template. These findings suggest that there is at least one key acetylation event that is needed to assemble a functional transcription preinitiation complex with a chromatin template.

Acetyl Coenzyme A↗
PubMed2000

Formaldehyde-mediated aggregation of protein antigens: comparison of untreated and formalinized model antigens.

A formaldehyde-mediated aggregation pathway (FMAP) is suggested as being primarily responsible for the aggregation of lyophilized tetanus toxoid (TT; a formalinized antigen) in the presence of moisture. The general occurrence of the FMAP was examined by using bovine serum albumin (BSA) and ribonuclease A (RNase) as model antigens; both protein antigens were formalinized according to a method commonly used to detoxify bacterial toxins. To clearly delineate the FMAP from other aggregation mechanisms, the aggregation kinetics and mechanism of both unmodified antigens (BSA and RNase) and formalinized antigens (f-BSA and f-RNase) were evaluated. We report that formaldehyde treatment introduces more rapid and extensive aggregation in antigens under conditions that favor the FMAP (i.e., 80% relative humidity and 37 degrees C). Consistent with formaldehyde-mediated crosslinking, f-antigen aggregates were covalent and non-disulfide-bonded, whereas BSA aggregates were disulfide-linked and RNase even did not aggregate under the same conditions. Coincorporation of amino acids (histidine and lysine), which strongly interact with formaldehyde, as well as prior antigen reduction with cyanoborohydride, significantly inhibited f-BSA aggregation, but showed no selective effect on BSA aggregation. Mechanistic analysis of f-BSA aggregates, inhibition studies, and similar reactivity of f-BSA with TT all confirmed the existence of the FMAP at moisture levels intermediate between the dry and solution state. This study demonstrates the potential for covalent reactions between formalinized protein antigens and neighboring chemical or biochemical species even after formalinization, and provides a general approach to inhibit the FMAP.

Amino Acids↗
PubMed2000

In vitro effects of Se-allylselenocysteine and Se-propylselenocysteine on cell growth, DNA integrity, and apoptosis.

Two previously unevaluated selenium compounds, Se-allylselenocysteine (ASC) and Se-propylselenocysteine (PSC), have been shown recently to be active in the chemoprevention of experimentally induced mammary carcinogenesis. Other than their potential as chemopreventive agents, little is known about the pharmacological properties of these compounds. In this article, we report on the in vitro effects of ASC and PSC on cell growth inhibition, apoptosis, and the induction of DNA damage. The effects of ASC and PSC were examined in two mouse mammary epithelial cell lines derived from mammary hyperplasias. These cell lines, designated TM2H and TM12, have mutant or wild-type p53, respectively. It was observed that ASC but not PSC reduced, in a concentration- and time-dependent manner, the number of adherent cells in culture, and this suppressive effect was more prominent in TM12 than in TM2H cells. ASC was also found to induce alkaline-labile DNA damage and the oxidation of pyrimidines, and it also increased the rate of apoptosis. These changes were not seen by exposure to PSC or the sulfur analog of ASC. However, additional data obtained from the intact rat mammary gland suggest that the loss of DNA integrity induced by ASC might not be manifest in vivo at doses of ASC that inhibit carcinogenesis.

Animals↗
PubMed2000

Integrin activation and focal complex formation in cardiac hypertrophy.

Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

Actins↗
PubMed2000

Helicobacter pylori-selective antibacterials based on inhibition of pyrimidine biosynthesis.

We report the discovery of a class of pyrazole-based compounds that are potent inhibitors of the dihydroorotate dehydrogenase of Helicobacter pylori but that do not inhibit the cognate enzymes from Gram-positive bacteria or humans. In culture these compounds inhibit the growth of H. pylori selectively, showing no effect on other Gram-negative or Gram-positive bacteria or human cell lines. These compounds represent the first examples of H. pylori-specific antibacterial agents. Cellular activity within this structural class appears to be due to dihydroorotate dehydrogenase inhibition. Minor structural changes that abrogate in vitro inhibition of the enzyme likewise eliminate cellular activity. Furthermore, the minimum inhibitory concentrations of these compounds increase upon addition of orotate to the culture medium in a concentration-dependent manner, consistent with dihydroorotate dehydrogenase inhibition as the mechanism of cellular inhibition. The data presented here suggest that targeted inhibition of de novo pyrimidine biosynthesis may be a valuable mechanism for the development of antimicrobial agents selective for H. pylori.

Amino Acid Sequence↗
PubMed2000

Insights into the rotary catalytic mechanism of F0F1 ATP synthase from the cross-linking of subunits b and c in the Escherichia coli enzyme.

The transmembrane sector of the F(0)F(1) rotary ATP synthase is proposed to organize with an oligomeric ring of c subunits, which function as a rotor, interacting with two b subunits at the periphery of the ring, the b subunits functioning as a stator. In this study, cysteines were introduced into the C-terminal region of subunit c and the N-terminal region of subunit b. Cys of N2C subunit b was cross-linked with Cys at positions 74, 75, and 78 of subunit c. In each case, a maximum of 50% of the b subunit could be cross-linked to subunit c, which suggests that either only one of the two b subunits lie adjacent to the c-ring or that both b subunits interact with a single subunit c. The results support a topological arrangement of these subunits, in which the respective N- and C-terminal ends of subunits b and c extend to the periplasmic surface of the membrane and cAsp-61 lies at the center of the membrane. The cross-linking of Cys between bN2C and cV78C was shown to inhibit ATP-driven proton pumping, as would be predicted from a rotary model for ATP synthase function, but unexpectedly, cross-linking did not lead to inhibition of ATPase activity. ATP hydrolysis and proton pumping are therefore uncoupled in the cross-linked enzyme. The c subunit lying adjacent to subunit b was shown to be mobile and to exchange with c subunits that initially occupied non-neighboring positions. The movement or exchange of subunits at the position adjacent to subunit b was blocked by dicyclohexylcarbodiimide. These experiments provide a biochemical verification that the oligomeric c-ring can move with respect to the b-stator and provide further support for a rotary catalytic mechanism in the ATP synthase.

Catalysis↗
PubMed2000

Selective inhibition of bacterial dihydroorotate dehydrogenases by thiadiazolidinediones.

Dihydroorotate dehydrogenase is a critical enzyme of de novo pyrimidine biosynthesis in prokaryotic and eukaryotic cells. Differences in the primary structure of the enzymes from Gram-positive and -negative bacteria and from mammals indicate significant structural divergence among these enzymes. We have identified a class of small molecules, the thiadiazolidinediones, that inhibit prototypical enzymes from Gram-positive and -negative bacteria, but are inactive against the human enzyme. The most potent compound in our collection functioned as a time-dependent irreversible inactivator of the bacterial enzymes with k(inact)/K(i) values of 48 and 500 M(-1) sec(-1) for the enzymes from Escherichia coli and Enterococcus faecalis, respectively. The data presented here indicate that it is possible to inhibit prokaryotic dihydroorotate dehydrogenases selectively while sparing the mammalian enzyme. Thus, this enzyme may represent a valuable target for the development of novel antibiotic compounds.

Anti-Bacterial Agents↗
PubMed2000

Structure and expression of the human MEP1A gene encoding the alpha subunit of metalloendopeptidase meprin A.

The human genome contains several sequences that are similar to the MEP1A gene encoding the alpha subunit of metalloendopeptidase meprin A. We now report the first genomic structure for the human MEP1A gene that maps to chromosome 6p21. The gene spans approximately 45 kb and consists of 14 exons and 13 introns. Overall, about 6.7% (3 kb) of the MEP1A gene corresponds to the exon sequences. Tissue specificity of the MEP1A gene expression was examined by dot blot analysis of poly(A) RNA from 50 different human tissues. The MEP1A mRNA was detected for the first time in kidney and appendix in addition to colon and small intestine previously known to express the gene. The elucidated gene structure and tissue-specific expression of the MEP1A gene set the stage for investigating regulation and function of the gene and related sequences in the human genome.

Amino Acid Sequence↗
PubMed2000

Retinoid signaling is required to complete the vertebrate cardiac left/right asymmetry pathway.

Vitamin A-deficient (VAD) quail embryos have severe abnormalities, including a high incidence of reversed cardiac situs. Using this model we examined in vivo the physiological function of vitamin A in the left/right (L/R) cardiac asymmetry pathway. Molecular analysis reveals the expression of early asymmetry genes activin receptor IIa, sonic hedgehog, Caronte, Lefty-1, and Fgf8 to be unaffected by the lack of retinoids, while expression of the downstream genes nodal-related, snail-related (cSnR), and Pitx2 is altered. In VAD embryos nodal expression in left lateral plate mesoderm (LPM) is severely downregulated and the expression domain altered during neurulation. Similarly, the expression of cSnR in the right LPM and of Pitx2 in the left side posterior heart-forming region (HFR) is downregulated in the VAD embryos. The lack of retinoids does not cause randomization or ectopic expression of nodal, cSnR, or Pitx2. At the six- to eight-somite stage nodal is expressed transiently in the left posterior HFR of normal quail embryos; this expression is missing in VAD embryos and may be linked to the loss of Pitx2 expression in this region of VAD quail embryos. Administration of retinoids to VAD embryos prior to the six-somite stage rescues the expression of nodal, cSnR, and Pitx2 as well as the randomized VAD cardiac phenotype. There is an absolute requirement for retinoids at the four- to five-somite developmental window for cardiogenesis and cardiac L/R specification to proceed normally. We conclude that retinoids do not regulate the left/right-specific sidedness assignments for expression of genes on the vertebrate cardiac asymmetry pathway, but are required during neurulation for the maintenance of adequate levels of their expression and for the development of the posterior heart tube and a loopable heart. Cardiac asymmetry may be but one of several critical events regulated by retinoid signaling in the retinoid-sensitive developmental window.

Activin Receptors, Type II↗
PubMed2000

Role of lys100 in human dihydroorotate dehydrogenase: mutagenesis studies and chemical rescue by external amines.

Chemical modification, mutagenesis, chemical rescue, and isotope effect studies are used to identify and probe the roles of several conserved amino acid groups in catalysis by human dihydroorotate dehydrogenase. Time- and pH-dependent inactivation of human dihydroorotate dehydrogenase by trinitrobenzenesulfonate implicates at least one critical lysyl residue in catalysis. Of four highly conserved lysines, only the cognate of Lys255 was previously suggested to have catalytic functionality. We now show that replacement of either Lys184 or Lys186 by mutagenesis does not impact, whereas substitution of Lys100 abolishes, enzymatic activity. However, activity is partially restored to K100C (or K100A) by inclusion of exogenous primary amines in reaction mixtures. This rescued activity saturates with respect to numerous amines and exhibits a steric discrimination reflected in K(d,(amine)) values. For all amines, rescued k(cat) values were only approximately 10% of wild type and independent of amine basicity. K(M) values for dihydroorotate and coenzyme Q(0) were similar to wild type. Thus, exogenous amines (as surrogates for Lys100) apparently complement a chemical, not binding, step(s) of catalysis, which does not entail proton transfer. In support of this postulate, solvent kinetic isotope effect analysis indicates that Lys100 stabilizes developing negative charge on the isoalloxazine ring of flavin mononucleotide during hydride transfer, as has been observed for a number of flavoprotein oxidoreductases. Ser215 of human dihydroarotate dehydrogenase (DHODase) was also studied because of its alignment with the putative active-site base Cys130 of Lactococcus lactisDHODase. Substantial retention of activity by S215C, yet complete loss of activity for S215A, is consistent with Ser215 serving as the active-site base in the human enzyme.

Amines↗
PubMed2000

Effects of Cu2+ on root growth, cell division, and nucleolus of Helianthus annuus L.

The effects of different concentrations (10-5 - 10-2 M) of copper sulfate on root growth, cell division and nucleoli in root-tip cells of Helianthus annuus L. were investigated. Cu had an inhibitory effect on the root growth at 10-4 - 10-2 M during the entire treatment. Cu has toxic effects on chromosomal morphology including anaphase bridges and chromosome stickiness and on nucleoli, causing some similar silver-stained particulate material scattered in the nuclei. Once the nucleolus is poisoned, showing some silver-stained particles scattered in the nucleus, the root growth of H. annuus is obviously inhibited. And once more silver-stained particles appear in the nucleus, the root growth is almost or completely stopped. The possible mechanism of the Cu poisoning of root-tip cells of H. annuus is also briefly discussed.

Cell Division↗