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Biomedical subjects

J Xia

Publications and source records attributed to J Xia.

At least 127 records · Page 7Linked to original sources

[Study of physiological parameters of velopharyngeal function by nasopharyngeal fibroscope].

OBJECTIVE: Velopharyngeal incompetency (VPI) could be found in certain healthy people when some vowels were produced. Since neither asophia nor organic deformity do they have, it should be considered as physiological VPI. VPI which exists commonly in patients with cleft palate is also an unsatisfactory manifestation after palatoplasty. In order to distinguish between physiological VPI and pathological VPI in patient with cleft palate and establish an objective criterion, it is necessary to assess the occurrence and extent of VPI in healthy people. METHODS: The velopharyngeal function of 890 subjects with normal speech was studied dynamically by nasopharyngeal fiberscope (NPF). Two vowels /i/ and /u/ were examined. The rates of velopharyngeal incompetence (RVPI) of vowel /i/ and /u/ were analyzed. RESULTS: VPI was found in 117 (13.15%) when vowel /i/ was produced. VPI was occurred in 100 (11.24%) when /u/ was produced. The RVPI mean of vowel /i/ is 11.285% +/- 7.248 in 112 subjects, while that of /u/ is 9.066% +/- 6.162 in 96. No significant difference was obtained in age or sex. CONCLUSION: It can be used to evaluate the velopharyngeal function after palatoplasty as physiological parameters.

Adult↗

[The evaluation of computer-aided simulating system in orthognathic surgery]

OBJECTIVE: The purpose of this study is to evaluate the reliabillty of computer-aided simulating system for orthognathic system. METHODS: 24 cases with dentofacial deformities were undergone treatment of orthognathic surgery.The presurgical cephalograms and profiles were input to the computer and were digitized.The simulated profiles and cephalometric analysis were obtained by the simulating system,and computer with the actual posttreatment cephalograms. RESULTS: The prodicted and actual posttreatment soft tissue line drawings were quite similar in all areas except for the lower lip region. CONCLUSION: In all cases,the actual images were judged more esthetic than the predicted images. It allayed the fears that the computer generated predictions were unrealistically and ideal.

Journal Article↗

Molecular pharmacology of UK-118, 434-05, a permanently charged amlodipine analog.

We studied the effects of UK-118, 434-05, a permanently charged form of amlodipine, on recombinant smooth muscle and cardiac L-type calcium channels to determine the distinct modulatory properties of the ionized form of amlodipine. We found that the short distance between the permanent charge group and the active dihydropyridine (DHP) ring of UK-118, 434-05 reduces the potency of this compound as an inhibitor of smooth muscle (alpha(1c-b)) L-type channels, and is similar to the effects of other charged DHP derivatives on cardiac (alpha(1c-a)) L-type channels. However, we found surprisingly that the tonic block of cardiac (alpha(1c-a)) L-type channels was more pronounced than the tonic block of smooth muscle (alpha(1c-b)) L-type channels. This result contrasts with the previously reported subunit-specificity of neutral DHP compounds, and suggests that interactions between the amlodipine charge group and site(s) on the L-type channel alpha1 subunit distinguish the action of charged from neutral DHPs and may contribute to amlodipine's unique pharmacological profile.

Amlodipine↗

Apolipoprotein(a) attenuates endogenous fibrinolysis in the rabbit jugular vein thrombosis model in vivo.

BACKGROUND: In many case-control as well as epidemiological studies, increased lipoprotein(a) [Lp(a)] levels are considered to constitute an independent risk factor for premature coronary artery and cerebrovascular disease. Lp(a) resembles an LDL particle with an additional linked protein [apolipoprotein(a), apo(a)], whose molecular structure has been demonstrated to be homologous to the fibrinolytic proenzyme plasminogen. Because of the high similarity between plasminogen and apo(a), apo(a) may potentially interfere in the fibrinolytic system by competing with plasminogen for fibrin binding sites. In vitro studies have demonstrated that Lp(a) indeed competes with plasminogen binding to fibrin and inhibits tissue plasminogen activator (TPA)-mediated activation of plasminogen. No direct in vivo studies to test this hypothesis have been performed. METHODS AND RESULTS: To test this hypothesis, we studied the effect of a recombinant form of apo(a) on endogenous and TPA-mediated thrombolysis in an in vivo model of experimental venous thrombosis. Thrombi containing either 16 microg r-apo(a), 8 microg r-apo(a), or vehicle (HEPES-buffered saline, control) were formed in the jugular veins of a rabbit and showed significantly reduced endogenous thrombolysis after 60 minutes in a dose-dependent fashion, ID 2.7+/-0.9% and 4.6+/-1.8%, respectively, versus 7.4+/-1.6% of that of the control. High concentrations of incorporated apo(a) significantly reduced TPA-induced thrombolysis (12.2+/-2.5% versus 22.2+/-2.6% in the control thrombi), but no effect of lower concentrations of incorporated r-apo(a) was demonstrated on the exogenous TPA-induced thrombolysis. CONCLUSIONS: The present study demonstrates the attenuation of endogenous fibrinolysis by apo(a) in an in vivo model of experimental venous thrombosis, lending support to the proposed mechanism of impaired fibrinolysis by which Lp(a) may contribute to atherothrombotic disorders.

Animals↗

Tau-like proteins in the nervous system of goldfish.

This report describes the presence of a group of tau-like proteins (TLPs) in goldfish central nervous system. The TLPs were immunoreactive with antibodies that recognized the carboxy-terminal domain of mammalian tau, but not with antibodies that recognized the amino-terminus. The TLPs of goldfish exhibited the basic properties of tau proteins including neuronal specificity, structural heterogeneity, heat stability and the ability to co-assemble with tubulin. We propose that TLPs may represent a precursor of tau, that share the microtubule binding domain and the carboxy-terminal domain with mammalian tau proteins. In contrast the amino-terminus of the TLPs is much shorter and may represent a more variable domain of tau proteins.

Animals↗

Isolation and characterization of a new chromosome 8q24.1 band-specific microsatellite polymorphism.

A clone, containing a 24-dinucleotide (CA)-repeat sequence, was isolated from chromosome 8q24.1 band-specific pUC19 library. It was localized to target chromosome using human-rodent hybrid cell panel. Eleven alleles were estimated from 56 unrelated individuals and the heterozygosity reaches 0.835. Linkage analysis of 11 Chinese pedigrees showed significant evidence for linkage of this new marker to three dinucleotide repeat markers at 8q23-24.1 region, with the most likely position of the marker between D8S85 and D8S199.

Alleles↗

[An experimental study of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of Lewis lung carcinoma].

OBJECTIVE: The inhibition effect of angiogenesis inhibitor TNP-470 on tumor growth and metastasis was studied using Lewis lung carcinoma. METHODS: Lewis lung carcinoma cells(2.4 x 10(6)/mouse) were inoculated subcutaneously to 20 mice, they were randomized into 2 groups. From the 2nd day, the treated group was given 40 mg/kg of TNP-470 s.c. q.o.d. (8 times) and the control group was given vehicle only (3% ethanol). On the 22nd day, the weight of the subcutanous tumors and the lung metastasis rates of the 2 groups were detected. The results were analysed by Student-t and chi 2 test. RESULTS: The tumor weight of the control and treated group was 3.77 +/- 1.05 g and 1.98 +/- 0.96 g, respectively (P = 0.0009). The lung metastasis rate of the control and treated group was 80%(8/10) and 30%(3/10), respectively (P = 0.03). CONCLUSION: These results suggest that the angiogenesis inhibitor TNP-470 has a strong inhibitory effect both on growth of the primary tumor and metastasis of Lewis lung carcinoma.

Animals↗

[Isolation of band-specific (CA)n microsatellites from human chromosome 8q24.1].

Fourty eight recombinant plasmids containing CA repeats were isolated from human chromosome 8q24.1 band-specific pUC19 library. Among them, inserted DNA fragments from 12 plasmids were sequenced, and one new highly polymorphic (CA)n microsatellite was obtained (coding: D8S7F). It contained 11 alleles. The estimated heterozygosity reached 0.84 and 0.83 among Chinese Han Nationality people and American Anglo-Saxons respectively. It was assigned to chromosome 8 by using a human-rodent hybrid cell panel.

Base Sequence↗

[SCA1, SCA2, MJD/SCA3 (CAG)n mutation detection and analysis in patients with hereditary spinocerebellar ataxia from Chinese families].

OBJECTIVE: To assess the frequency of the SCA1, SCA2, MJD/SCA3 CAG trinucleotide repeat expansions ((CAG)n) among individuals diagnosed with hereditary spinocerebellar ataxia (SCA) from Chinese families. METHOD: The SCA1, SCA2, MJD/SCA3 (CAG)n mutation were detected with the polymerose chain reaction (PCR), denaturing polyacrylamide gel and silver staining technique in 79 patients with autosomal dominant SCA from 50 Chinese families. RESULTS: Among 50 kindreds, 2% (1/50) had the SCA1, (CAG)n, 6% (3/50) had the SCA2, (CAG)n, whereas 48% (24/50) were positive for the MJD/SCA3 (CAG)n. Thus, together SCA1, SCA2, and MJD/SCA3 represent 56% (28/50) of the autosomal dominant ataxias in our group. In two SCA1 patients the CAG repeat was expanded to 53-62 repeats, whereas in normal ivdividuals was 12-36 repeats. In seven SCA2 patients the CAG repeat was expanded to 43-47 repeats, whereas in normal ivdividuals was 22-30 repeats. In forty-two MJD/SCA3 patients the CAG repeat was expanded to 63-78 repeats, whereas in normal ivdividuals was 15-38 repeats. The SCA1, SCA2, MJD/SCA3 (CAG)n mutation were excluded in the other 28 SCA patients from 22 families. CONCLUSION: The frequency of MJD/SCA3 is substantially higher than that of SCA1 and SCA2 in the autosomal dominant SCA from Chinese families. Chinese patients with MJD/SCA3 are non-Portuguese patients with MJD/SCA3. Clinical expressions of the various SCAs overlap one another, making a diagnostic classification based on phenotype inaccurate in many instances. It is important for SCA clinical study to make a SCA gene diagnosis and genomic classification.

Adolescent↗

[The effects of He-Ne laser on the revascularization of the distal part of the subdermal vascular network skin flap].

The distal part of the subdermal vascular network (SVN) random skin flap on the rabbit was radiated with He-Ne laser at an energy density of 3.15 J/cm2. The blood vessels of the flap were perfused with Chinese ink. Histological examinations and image analysis were applied to evaluate the effects of He-Ne laser radiation on the SVN skin flap. It was found that the revascularization and the survival rate of the SVN random skin flap were highly related with the proportion of the length to width of the flap in the early stage. The radiation of the He-Ne laser could improve the microcirculation of the flap and increase its survival rate, which was mainly resulted from dilation of the blood vessels, especially the veins, and anastomosis of the vessels between the flap and the recipient site.

Animals↗

Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human.

Different isoenzymes of pyruvate dehydrogenase kinase (PDK) inhibit the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1alpha subunit, thus contributing to the regulation of glucose metabolism. By positional cloning in the 7q21.3-q22.1 region linked with insulin resistance and non-insulin-dependent diabetes mellitus in the Pima Indians, we identified a gene encoding an additional human PDK isoform, as evidenced by its amino acid sequence identity (>65%) with other mammalian PDKs, and confirmed by biochemical analyses of the recombinant protein. We performed detailed comparative analyses of the gene, termed PDK4, in insulin-resistant and insulin-sensitive Pima Indians, and detected five DNA variants with comparable frequencies in both subject groups. Using quantitative reverse transcription polymerase chain reaction, we found that the variants identified in the promoter and 5'-untranslated region did not correlate with differences in mRNA level in skeletal muscle and adipose tissue. We conclude that alterations in PDK4 are unlikely to be the molecular basis underlying the observed linkage at 7q21.3-q22.1 in the Pima Indians. Information about the genomic organization and promoter sequences of PDK4 will be useful in studies of other members of this family of mitochondrial protein kinases that are important for the regulation of glucose metabolism.

Adipose Tissue↗

Regulation of the B cell response to T-dependent antigens by classical pathway complement.

Mice deficient in complement components C3 (C3 -/-) and C4 (C4 -/-) were found to have a profound defect in their Ab response to a T-dependent Ag (bacteriophage (phi X174). Characterization of the deficient mice demonstrated a diminished level of peanut agglutinin+ germinal centers and a failure in isotype switching despite normal B cell signaling in vitro. The nature of the defect was found to lie at the B cell level, as the T cells were primed in C3- and C4-deficient mice as well as those in wild-type mice. These results, and the finding that the defect could be partly reversed by a 10-fold increase in Ag dose, support the hypothesis that covalent attachment of complement ligands, i.e., C3b and C3d to the Ag-Ab complex, increases its immunogenicity.

Animals↗

Polymers with Very Low Polydispersities from Atom Transfer Radical Polymerization

A radical polymerization process that yields well-defined polymers normally obtained only through anionic polymerizations is reported. Atom transfer radical polymerizations of styrene were conducted with several solubilizing ligands for the copper(I) halides: 4,4'-di-tert-butyl, 4,4'-di-n-heptyl, and 4,4'-di-(5-nonyl)-2,2'-dipyridyl. The resulting polymerizations have all of the characteristics of a living polymerization and displayed linear semilogarithmic kinetic plots, a linear correlation between the number-average molecular weight and the monomer conversion, and low polydispersities (ratio of the weight-average to number-average molecular weights of 1.04 to 1.05). Similar results were obtained for the polymerization of acrylates.

Journal Article↗

Carbon monoxide dehydrogenase from Clostridium thermoaceticum: quaternary structure, stoichiometry of its SDS-induced dissociation, and characterization of the faster-migrating form.

The molecular mass (M(r)) of the nickel- and iron-sulfur-containing enzyme CO dehydrogenase from Clostridium thermoaceticum was determined by sedimentation equilibrium ultracentrifugation to be 300,000 +/- 30,000 Da. Since the enzyme is known to contain equal numbers of two types of subunits (M(r) = 82,000 Da for alpha and 73,000 Da for beta), this indicates an alpha 2 beta 2 quaternary structure. The enzyme was previously thought to have an alpha 3 beta 3 structure because it migrates through calibrated size-exclusion chromatographic columns with an apparent M(r) of about 420,000 Da. The disproportionately fast migration rate suggests that the enzyme is nonspherical. SDS induces the dissociation of an alpha subunit, yielding a stable species called FM-CODH. FM-CODH had a molecular mass of 210,000 +/- 30,000 Da, indicating an alpha 1 beta 2 structure. It contained 2.1 +/- 0.3 Ni and 16 +/- 3 Fe per alpha 1 beta 2, exhibited S-->Fe charge-transfer transitions typical of Fe-S proteins, and afforded the gav = 1.82, 1.86, and 1.94 EPR signals. Quantitation of the 1.82 and (1.94 +/- 1.86) signals afforded 0.35 and 1.9 spin/alpha 1 beta 2, respectively. FM-CODH samples exhibited CO oxidation activity, but little CO/acetyl-CoA exchange activity. Some FM-CODH samples exhibited CO oxidation activities as high as native enzyme. These results, along with the quantified spin intensities of the EPR signals, indicate that FM-CODH contains the B- and C-clusters and suggest that these clusters are located in the beta subunit. The alpha subunit that dissociated during formation of FM-CODH is not required for CO oxidation activity. FM-CODH is either devoid of A-clusters, or if such clusters are present, they have lost their ability to exhibit substantial NiFeC signals and CO/acetyl-CoA exchange activity. Incubating FM-CODH and alpha yielded a species that migrated through polyacrylamide gels at the same rate as native enzyme, and had a molecular mass indicating an alpha 2 beta 2 structure. Thus, the SDS-induced dissociation of the enzyme appears to be reversible.

Aldehyde Oxidoreductases↗

Drug delivery systems: water soluble taxol 2'-poly(ethylene glycol) ester prodrugs-design and in vivo effectiveness.

Water soluble 2'-taxol poly(ethylene glycol) (PEG) esters have been synthesized and shown to function in vitro as prodrugs. However, in vivo experiments clearly establish that in order for these prodrugs to behave in a predictable fashion, the molecular weight of PEG must be of such magnitude so as to maintain a t1/2(circulation) > t1/2(hydrolysis). When PEG derivatives of molecular weight approximately 40 kDa were employed with paclitaxel, ca. 4% by weight of paclitaxel was carried by the water soluble prodrug form, and equivalent in vivo toxicity and increased life expectancy in the P388-treated mouse was observed. An effective method for prescreening prodrugs was found to be the acute murine lethality, which reflects the equivalency of the solubilized transport form and the native drug.

Animals↗

Fumonisin toxicity and sphingolipid biosynthesis.

Fumonisins are inhibitors of sphinganine (sphingosine) N-acyltransferase (ceramide synthase) in vitro, and exhibit competitive-type inhibition with respect to both substrates of this enzyme (sphinganine and fatty acyl-CoA). Removal of the tricarballylic acids from fumonisin B1 reduces the potency by at least 10 fold; and fumonisin A1 (which is acetylated on the amino group) is essentially inactive. Studies with diverse types of cells (hepatocytes, neurons, kidney cells, fibroblasts, macrophages, and plant cells) have established that fumonisin B1 not only blocks the biosynthesis of complex sphingolipids; but also, causes sphinganine to accumulate. Some of the sphinganine is metabolized to the 1-phosphate and degraded to hexadecanal and ethanolamine phosphate, which is incorporated into phosphatidylethanolamine. Sphinganine is also released from cells and, because it appears in blood and urine, can be used as a biomarker for exposure. The accumulation of these bioactive compounds, as well as the depletion of complex sphingolipids, may account for the toxicity, and perhaps the carcinogenicity, of fumonisins.

Amidohydrolases↗

Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen.

Covalent attachment of activated products of the third component of complement to antigen enhances its immunogenicity, but the mechanism is not clear. This effect is mediated by specific receptors, mCR1 (CD35) and mCR2 (CD21), expressed primarily on B cells and follicular dendritic cells in mice. To dissect the role of mCR1 and mCR2 in the humoral response, we have disrupted the Cr2 locus to generate mice deficient in both receptors. The deficient mice (Cr2-/-) were found to have a reduction in the CD5+ population of peritoneal B-1 cells, although their serum IgM levels were within the range of normal mice. Moreover, Cr2-/- mice had a severe defect in their humoral response to T-dependent antigens that was characterized by a reduction in serum antibody titers and in the number and size of germinal centers within splenic follicles. Reconstitution of the deficient mice with bone marrow from MHC-matched Cr2+/+ donors corrected the defect, demonstrating that the defect was due to B cells themselves. These results indicate an obligatory role of B cell complement receptors in responses of the B cells to protein antigens.

Animals↗