Biomedical subjects

C Xu

Publications and source records attributed to C Xu.

At least 127 records · Page 7Linked to original sources

PubMed2000

[Quantitative and immunohistochemical analysis of endothelin-1 in oral submucous fibrosis].

OBJECTIVE: This experiment is carried out to investigate roles of endothelin-1 (ET-1), a potent vasoconstrictor and mitogenic peptide, in fibrosis and collagen production. METHODS: 30 cases of oral submucous fibrosis(OSF), 10 cases of oral lichen planus (OLP) and 10 cases of normal control, were studied by means of SABC immunohistochemical method with polyclonal antisera to ET-1 and using image pattern analysis technique. RESULTS: 1. Oral mucosa from OLP and normal control expressed very little ET-1. By contrast, there was striking expression of ET-1 in oral mucosa from OSF; 2. The cellular content of ET-1 in OSF was significantly higher than that in normal control (P < 0.01), while the cellular content of ET-1 in the early and moderate stages OSF were significantly higher than that in the advanced stage(P < 0.01); 3. The cellular content of ET-1 in the early and moderate stages OSF were significantly higher than that in OLP(P < 0.01); 4. There was a significantly positive correlation between cellular contents of epithelia and interstitial(P < 0.05). CONCLUSION: These findings suggest that cell-specific expression of ET-1 may play a role in pathogenesis of OSF.

Endothelin-1↗

PubMed1999

The CTLA-4 gene is associated with multiple sclerosis.

We have investigated whether three intragenic polymorphisms of the CTLA-4 gene, a C/T base exchange in the promoter (p.-318), an A/G substitution in exon 1 (p.49) and a dinucleotide repeat polymorphism in exon 4 (p.642), were associated with genetic susceptibility to multiple sclerosis (MS). We observed a significant association (p < 0.05) for homozygosity for the G49 allele in a case-control analysis of 378 MS patients and 237 controls, and a transmission disequilibrium (p < 0.02) for the G49 allele in 31 MS families. This was further corroborated by evidence for linkage by the affected pedigree member (APM) analysis (p < 0.0002) and a transmission distortion (p < 0.05) of the exon 4(642) polymorphism. Sequencing of the promoter, the first and second exons and the parts of the first intron revealed no further polymorphisms. Our results suggest that a dysregulation of CTLA-4-driven downregulation of T-cell activation could be involved in the pathogenesis of MS.

Abatacept↗

PubMed1999

Characterization of peroxidase:anti-peroxidase immune complexes by capillary zone electrophoresis and high-performance size-exclusion chromatography.

Determination of the molecular constituents of commercial peroxidase:anti-peroxidase (PAP) preparations is necessary for the proper interpretation of PAP applications based on competitive binding assay. Capillary zone electrophoresis with field 300 V/cm, 40 cm capillary length (20 cm effective length), and high-performance size exclusion chromatography equipped with Superose 12 HR10/30 column revealed that a PAP preparation used for Fc gamma receptor studies contained multiple sizes of immune complexes, an excess amount of free peroxidase, and little or no free anti-peroxidase antibody. The antibody:antigen ratios of the three major immune complex components were 2:2, 1:2, and 1:1. These techniques provide useful methods of qualitative, as well as quantitative analysis of PAP preparations.

Antigen-Antibody Complex↗

PubMed1999

Dielectrophoresis of human red cells in microchips.

The dielectric properties of human red cells are strongly affected by the applied electric field, especially the frequency. Under the high frequency, the cells are acted on by positive dielectrophoresis (DEP) force and move to the tip region of the interdigitated electrode where the electric field is strongest. The cells are acted on by negative DEP force and aggregated in the "bay" zone between the neighboring electrode castellation tips and the surface of the electrodes. The patterns formed by DEP force are identical with the distribution of the electric field.

Electrodes↗

PubMed1999

Immune complex size and complement regulate cytokine production by peripheral blood mononuclear cells.

We have previously shown that immune complexes isolated from children with juvenile rheumatoid arthritis are heterogeneous in their size, composition, and proinflammatory capacities. The experiments described here were undertaken to clarify further the roles of size and composition in determining the proinflammatory effects of immune complexes. We incubated peripheral blood mononuclear cells (PBMCs) with different soluble immune complex preparations: opsonized complexes, which were formed in the presence of serum, unopsonized complexes, which were formed in the absence of serum, and immune precipitates solubilized by complement after their formation. ELISA assays showed that immune complexes formed in the presence of complement were less efficient than unopsonized complexes in inducing IL-1beta and IL-8 secretion from leukocytes. Solubilized immune precipitates showed intermediate capacity to stimulate the release of both cytokines. Complexes formed in heat-inactivated serum were as efficient as unopsonized complexes in eliciting cytokine secretion from the cells. The capacity of complement to regulate cytokine secretion from leukocytes was related, at least in part, to immune complex size. Sucrose density gradients showed unopsonized complexes and solubilized immune precipitates were larger than opsonized immune complexes. In contrast, fluid-phase binding of C4 to immune complexes, which did not appreciably change immune complex size, substantially increased IL-1beta secretion from PBMC.

Antigen-Antibody Complex↗

PubMed1999

Tropomyosin positions in regulated thin filaments revealed by cryoelectron microscopy.

Past attempts to detect tropomyosin in electron micrograph images of frozen-hydrated troponin-regulated thin filaments under relaxing conditions have not been successful. This raised the possibility that tropomyosin may be disordered on filaments in the off-state, a possibility at odds with the steric blocking model of muscle regulation. By using cryoelectron microscopy and helical image reconstruction we have now resolved the location of tropomyosin in both relaxing and activating conditions. In the off-state, tropomyosin adopts a position on the outer domain of actin with a binding site virtually identical to that determined previously by negative staining, although at a radius of 3.8 nm, slightly higher than found in stained filaments. Molecular fitting to the atomic model of F-actin shows that tropomyosin is localized over sites on actin subdomain 1 required for myosin binding. Restricting access to these sites would inhibit the myosin-cross-bridge cycle, and hence contraction. Under high Ca(2+) activating conditions, tropomyosin moved azimuthally, away from its blocking position to the same site on the inner domain of actin previously determined by negative staining, also at 3.8 nm radius. These results provide strong support for operation of the steric mechanism of muscle regulation under near-native solution conditions and also validate the use of negative staining in investigations of muscle thin filament structure.

Actins↗

PubMed1999

Experimental analysis of distortion of magnetoencephalography signals by the skull.

OBJECTIVES: Magnetoencephalography (MEG) signals are, on theoretical grounds, thought to be relatively undistorted by the skull in contrast to electroencephalographic (EEG) signals. This assumption was experimentally tested in an animal preparation with a brain similar to the human brain in many respects. METHODS: Possible skull effects on MEG were evaluated directly using an in vivo porcine preparation, by measuring the somatic evoked magnetic field (SEF) above the skull with and without the skull under, otherwise, the same condition. RESULTS: The SEF was virtually undistorted by the skull with no obvious visible change in its waveform and amplitude under these two conditions. However, there was some small, but significant attenuation when the skull was removed, the distortion being greater for deeper sources. CONCLUSION: Our results are consistent with a theoretical expectation that the skull should be virtually 'transparent' to the magnetic fields for shallow sources, but less so for fields generated by deeper sources.

Animals↗

PubMed1999

Comparison of MEG and EEG on the basis of somatic evoked responses elicited by stimulation of the snout in the juvenile swine.

OBJECTIVE: Some basic characteristics of magnetoencephalographic (MEG) and electroencephalographic (EEG) signals were studied by comparing somatic evoked fields (SEFs) and potentials (SEPs) elicited by electrical stimulations of different areas of the snout in piglets. METHODS: SEFs were measured with and without an intact skull, whereas SEPs were measured on the skull and cortex (Electrocorticograms - ECoG) and within the cortex of the same animal. RESULTS: The SEFs above the skull and dura were very similar to each other in temporal waveform and spatial topography, indicating small effects of the skull. They both revealed very similar somatotopic projections of the snout. The SEPs on the skull and cortex were, in contrast, clearly different in their amplitudes as well as temporal and spatial morphologies, indicating significant effects of the skull. However, an early component of the SEP on the skull revealed a somatotopic representation of the snout, indicating that EEG can be also useful for inferring cortical projection areas. Discrepancies in their maps were due to predominance of the potentials produced by currents in the gyral cortex. The projection sites inferred from SEFs were quite accurate in comparison to those inferred from ECoGs and intracortical SEPs. CONCLUSION: The similarities and differences clearly point out the complementary nature of MEG and EEG.

Animals↗

PubMed1999

Microscopic evidence against HIV-1 infection of germ cells or attachment to sperm.

For a number of years we have intensively investigated the localization of HIV-1 in male genital tract tissues and secretions using a variety of microscopy techniques including immunocytochemistry, in situ hybridization, in situ PCR and electron microscopy. Our studies have failed to demonstrate an association between HIV-1 and either testicular germ cells or spermatozoa. In this article we present our results in the context of other related studies, and discuss the strengths and weaknesses of the techniques that have been used to address this important research question.

HIV Infections↗

PubMed1999

The up-regulation of endosomal-lysosomal components in amyloid beta-resistant cells.

The abundance of amyloid beta peptide (A beta) and the selective loss of neurons are characteristics of Alzheimer's disease. However, subpopulations of brain cells survive, including neurons near A beta-rich plaques. The surviving neurons may have gene expression profiles that allow them to be resistant to A beta toxicity. Here we use the differential display technique to compare the profiles of gene expression in an A beta-resistant cell line with its parental cells. Prominent among the changes are two components of the endosomal-lysosomal system, insulin growth factor II receptor/mannose-6-phosphate receptor and arylsulfatase B. Both are more highly expressed in the A beta-resistant clone, and arylsulfatase is inducible by A beta and hydrogen peroxide. Another lysosomal enzyme, beta-glucuronidase, is also up-regulated in A beta-resistant cells. These results are consistent with the observation that the endosomal-lysosomal system is highly activated in Alzheimer's disease brains, and they raise the possibility that the high expression of endosomal-lysosomal components is important for neuronal survival in the presence of A beta.

Amyloid beta-Peptides↗

PubMed1999

High calcium intake lowers apparent digestibility of energy in veal calves.

Veal calves aged 8 weeks were fed iso-energetic amounts of milk replacers with either a low (7.1 g of calcium/kg of air-dry diet) or a high concentration of calcium (11.6 g of calcium/kg of air-dry diet) for a period of 10 weeks. The extra calcium was added in the form of calcium formiate. Final body weight of the two dietary groups was similar. Faeces were collected during the final week of the trial. The high calcium diet raised faecal dry matter output by 87% and faecal energy by 70%. The extra output of faecal dry matter was composed of 36% and 37% of crude fat and ash, respectively. The extra faecal energy output was for 75% in the form of crude fat. The high versus low calcium intake not only depressed apparent digestibility of total lipids but also that of crude protein, carbohydrates and ash. It is concluded that a high calcium intake by veal calves reduced energy availability without affecting body weight gain.

Animals↗

PubMed1999

Persistence of human immunodeficiency virus in semen after adding indinavir to combination antiretroviral therapy.

Changes in human immunodeficiency virus (HIV) type 1 concentration and protease genotype were evaluated in semen specimens from 22 HIV-positive men before and 6 months after the addition of indinavir to dual nucleoside therapy. Seminal HIV was detected by polymerase chain reaction analysis for DNA or RNA for 59% of men before combination treatment and persisted at 6 months for 31% of the men who initially had seminal HIV detected (P = .026). The maximum levels of cell-free RNA, cell-associated RNA, and proviral DNA in semen before treatment and at 6 months were 400,000 and 10,000 copies/mL, 70,000 and 27,000 copies/mL, and 80,000 and 3,000 copies/mL, respectively. Three of the four men with persistent seminal DNA had plasma viral loads of > 10,000 copies/mL before treatment. One patient who became intolerant to indinavir had seminal HIV RNA detected by PCR analysis after 6 months. Although none of the cultures of semen specimens from the four men with PCR analysis-detectable seminal DNA after 6 months yielded HIV, indinavir resistance mutations were identified in a seminal leukocyte DNA specimen from one patient, and a second patient whose therapy was switched to saquinavir had different protease inhibitor resistance mutations in seminal and blood leukocyte DNA specimens. HIV-1 protease inhibitor resistance mutants may emerge in the semen of patients receiving combination therapy.

Anti-HIV Agents↗

PubMed1999

Increasing the thermostability of D-xylose isomerase by introduction of a proline into the turn of a random coil.

Thermostability can be increased by introducing prolines at suitable sites in target proteins. Two single (G138P, G247D) mutants and one double (G138P/G247D) mutant of xylose isomerase from Streptomyces diastaticus No.7, strain M1033 have been constructed by site-directed mutagenesis. With respect to the wild-type enzyme, G138P showed about a 100% increase in thermostability, and G247D showed an increased catalytic activity. Significantly, the double mutant, G138P/G247D displayed even higher activity than G247D and better heat stability than G138P. Its half life was about 2.5-fold greater than the wild-type enzyme, using xylose as a substrate. Molecular modelling suggested that the introduction of a proline residue in the turn of a random coil may cause the surrounding conformation to be tightened by reducing the backbone flexibility. The change in thermostability can, therefore, be explained based on changes in the molecular rigidity. Furthermore, the improvements in the properties of the double mutant indicated that the advantages of two single mutants can be combined effectively.

Aldose-Ketose Isomerases↗

PubMed1999

Reconstruction of the human cerebral cortex from magnetic resonance images.

Reconstructing the geometry of the human cerebral cortex from MR images is an important step in both brain mapping and surgical path planning applications. Difficulties with imaging noise, partial volume averaging, image intensity inhomogeneities, convoluted cortical structures, and the requirement to preserve anatomical topology make the development of accurate automated algorithms particularly challenging. In this paper we address each of these problems and describe a systematic method for obtaining a surface representation of the geometric central layer of the human cerebral cortex. Using fuzzy segmentation, an isosurface algorithm, and a deformable surface model, the method reconstructs the entire cortex with the correct topology, including deep convoluted sulci and gyri. The method is largely automated and its results are robust to imaging noise, partial volume averaging, and image intensity inhomogeneities. The performance of this method is demonstrated, both qualitatively and quantitatively, and the results of its application to six subjects and one simulated MR brain volume are presented.

Algorithms↗

PubMed1999

Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells.

Molecular basis of native voltage-dependent K(+) (Kv) channels in smooth muscle cells (SMCs) from rat mesenteric arteries was investigated. The whole cell patch-clamp study revealed that a 4-aminopyridine-sensitive delayed rectifier K(+) current (I(K)) was the predominant K(+) conductance in these cells. A systematic screening of the expression of 18 Kv channel genes using RT-PCR technique showed that six I(K)-encoding genes (Kv1.2, Kv1.3, Kv1.5, Kv2.1, Kv2.2, and Kv3.2) were expressed in mesenteric artery. Although no transient outward Kv currents (I(A)) were recorded in the studied SMCs, transcripts of multiple I(A)-encoding genes, including Kv1.4, Kv3.3, Kv3.4, Kv4.1, Kv4.2, and Kv4.3 as well as I(A)-facilitating Kv beta-subunits (Kvbeta1, Kvbeta2, and Kvbeta3), were detected in mesenteric arteries. Western blot analysis demonstrated that four I(K)-related Kv channel proteins (Kv1.2, Kv1. 3, Kv1.5, and Kv2.1) were detected in mesenteric artery tissues. The presence of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 channel proteins in isolated SMCs was further confirmed by immunocytochemistry study. Our results suggest that the native I(K) in rat mesenteric artery SMCs might be generated by heteromultimerization of Kv genes.

4-Aminopyridine↗

PubMed1999

Abrogation of the Cripto gene in mouse leads to failure of postgastrulation morphogenesis and lack of differentiation of cardiomyocytes.

Cripto-1(Cr1) protein encoded by the tdgf1 gene, is a secreted growth factor that is expressed early in embryonic development and is re-expressed in some tumors of the breast and colon. During embryonic development, Cr1 is expressed in inner cell mass cells and the primitive streak, and later is restricted to the developing heart. To investigate the role of Cr1 during mouse development, mice were generated that contain a null mutation of both Cr1 genes, derived from homologous recombination in embryonic stem cells. No homozygous Cr1-/- mice were born, indicating that Cr1 is necessary for embryonic development. Embryos initiated gastrulation and some embryos produced mesoderm up to day E7.5. Increasingly aberrant morphogenesis gave rise to disordered neuroepithelium that failed to produce a recognizable neural tube, or head-fold. Although some biochemical markers of differentiating ectoderm, mesoderm and endoderm were expressed, all the cardiac-specific markers were absent from day E8.7 embryos: (&agr;)MHC, betaMHC, MLC2A, MLC2V and ANF, whereas they were expressed in wild-type embryos. The yolk sac and placental tissues continued development in the absence of the embryo until day E9.5 but lacked large yolk sac blood vessels. Chimeric mice were constructed by microinjection of double targeted Cr1(-/- )embryonic stem cells into normal C57BL/6 blastocysts. The Cr1 produced by the normal C57BL/6 cells fully rescued the phenotype of Cr1(-/-) cells, indicating that Cr1 protein acted in a paracrine manner. Cells derived from the embryo proliferated and migrated poorly and had different adhesion properties compared to wild type. Therefore, lethality in the absence of Cr1, likely resulted largely from defective precardiac mesoderm that was unable to differentiate into functional cardiomyocytes.

Alleles↗

PubMed1999

Cell cycle delay, mitochondrial stress and uptake of hydrophobic cations induced by sunscreens in cultured human cells.

Reports of systemic absorption of sunscreens prompted a study of the effects of emulsions of 3 commonly used sunscreens on cultured human cells; vegetable oil and paraffin oil were used as controls. Ethylhexyl p-methoxycinnamate (EHMC), octyl p-dimethylaminobenzoate (PABA) and oxybenzone (OB) inhibited cell growth and DNA synthesis and retarded cycle progression from G1 in the dose range 25-100 micrograms/mL. An extended period of exposure (up to 24 h) was required for maximum uptake of sunscreens and for inhibition of cell growth. Melano-cytes and fibroblasts tended to be more resistant than tumor cell lines (melanoma, cervical carcinoma). Sunscreens had no major effects on the transcription of certain genes, as judged by the activity of reporter constructs driven by the p53, c-fos and metal response (sheep metallothionein Ia promoter) elements and transfected into a human melanoma cell line (MM96L). The activity of the cytomegalovirus promoter was also not affected. A cell line (CI80-13S) with mitochondrial dysfunction was significantly more sensitive to growth inhibition by EHMC and PABA than the other cell lines tested. Treatment of MM96L with the mitochondrial inhibitor ethidium bromide sensitized the cells to killing by cotreatment with sunscreens, in association with increased cellular uptake of ethidium bromide. These results established conditions for studying the action of sunscreens on cultured human cells. Further studies are required to determine whether the mitochondrial stress and changes in drug uptake associated with sunscreens in the above cell lines are relevant to their action in vivo.

Cations↗

PubMed1999

[Effect of the herpes simplex virus I-thymidine kinase gene-ganciclovir system on the transplant of human ovarian cancer on the omentum of nude mice].

OBJECTIVE: To investigate the therapeutic effect of the herpes simplex virus I-thymidine kinase gene (HSV1-tk)/ganciclovir (GCV) system on human ovarian cancer. METHODS: The nude mice tumors were formed by injection of human ovarian cancer cell line AO and AO/HSV1-tkc (AO cells carried with HSV1-tk gene which was constructed in China) subcutaneously, and then were transplanted to the omentum of nude mice. The filter-passing culture fluid of VPC/HSV1-tkc was injected daily into the peritoneum of the nude mice in the group of in vivo. Finally, all of the three groups of nude mice (control, in vivo, ex vivo) accepted the treatment of GCV. RESULTS: The inhibitory rate of the RV/HSV1-tkc/GCV to AO tumors were 46.8%, and, only could the residual microscopic tumors be seen in most of the nude mice omentum transplanted with AO/HSV1-tkc tumor after GCV treatment. CONCLUSIONS: GCV could more effectively inhibit the growth of the human ovarian tumors carried with HSV1-tk gene which was transplanted onto the nude mice omentum than which transplanted subcutaneously; The application of the HSV1-tk/GCV system would be very promising in the gene therapy of ovarian cancer.

Animals↗