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Biomedical subjects

X Nie

Publications and source records attributed to X Nie.

27 records · Page 2Linked to original sources
PubMed1999

Regulation of VH gene repertoire and somatic mutation in germinal centre B cells by passively administered antibody.

Immunization with T-dependent antigens induces a rapid differentiation of B cells to plasmacytes that produce the primary immunoglobulin M (IgM) and IgG antibodies with low affinities for the immunogen. It is proposed that the IgG antibody forms immune complexes with the residual antigen which provide an important stimulus for the formation of germinal centres (GC) and the activation of somatic mutation. This hypothesis was tested by passive administration of hapten-specific antibody into mice shortly after the immunization with nitrophenyl (NP) coupled to chicken gamma globulin (NP-CGG) in an environment of limited T-cell help. Athymic mice that received normal T helper cells at 72 hr after the administration of antigen produced low levels of anti-NP antibody and the splenic GC formation was delayed until day 12 after the antigen administration. The analysis of VDJ segments from NP-reactive GC B cells showed very few mutations in the VH genes. Passive injection of anti-NP IgG1 monoclonal antibody - but, not IgM - stimulated the GC formation up to normal levels and the somatic mutation activity in the GC B cells was fully restored. In addition, GC B cells in the recipients of IgG1 antibody demonstrated a change in the usage of germline-encoded VH genes which was not apparent among the primary antibody-forming cells. These results suggest the existence of a specific feedback mechanism whereby the IgG antibody regulates the GC formation, clonotypic repertoire and somatic mutation in GC B cells.

Animals↗
PubMed1999

[Experiment and clinical application of targeting treatment with adriamycin magnetic albumin microspheres in human gastric carcinoma].

OBJECTIVE: To study the pharmacokinetics in experimental animals and observe the concurrent anticancer effects in human advanced gastric cancer as an adjuvant chemotherapy, when adriamycin magnetic albumin microspheres (ADM-MAM) were combined with external static magnetic fields. METHODS: The drug concentration of targeting tissues in the animals and the stability of ADM-MAM in human gastric juices were determined. Clinical and histopathological changes were observed in 55 cases of advanced gastric carcinomas after targeting treatment. RESULTS: The peak concentrations of the targeting tissue were highest after ADM-MAMs were administered for 2 hours and remained at the high level for a long time. ADM-MAM maintained its stability in human gastric juices. Targeting treatment improved the patients' symptoms, raised the rated of tumor resection, prolonged patients' lifetime, and enhanced histopathological effects (P < 0.01). CONCLUSIONS: The administration of ADM-MAM combined with the external static magnetic fields is effective for targeting location and is of clinical value as a preoperative adjuvant chemotherapy for human advanced gastric carcinoma.

Adolescent↗
PubMed1999

[Effects of tantalum and its oxide on exposed workers].

OBJECTIVE: To explore effects of tantalum and its oxide on the exposed workers. METHODS: Health examination for 113 workers exposed to tantalum and its oxide and a field survey for occupational hygiene in the workplace were carried out. RESULTS: Workplace air concentration of tantalum and its oxide averaged 0.1 - 7.6 mg/m(3). There was no significant difference in prevalence of symptoms and signs and biochemical, pulmonary function, chest X-ray and electrocardiograph examinations between the exposed and control workers. CONCLUSION: No adverse effect of tantalum and its oxide on the exposed workers was found.

Adolescent↗
PubMed1998

Anti-autolysis of trypsin by modification of autolytic site Arg117.

In order to improve the stability of trypsin, an approach to knock out the autolytic site has been carried out in this investigation. Compared with trypsins from other species, the autolytic site Arg117-Val118 of rat trypsin is the most interesting candidate to work on. The Arg117 residue was designed to be deleted or replaced by other amino acid residues to destroy the autolytic site. With DNA site-directed mutagenesis method, one deletion mutant and several replacement mutants were selected. After expression and purification, the kinetic and anti-autolytic properties of mutant trypsins were studied. No net charge difference of the trypsin molecules was observed by native PAGE analysis. Kinetic studies show that the activities of mutants vary from one another. R117L gives 32 times the activity of wild type trypsin while R117C has no detective activity. Among 8 selected mutants with characteristic properties, 7 of them give prolonged half life during anti-autolytic assay with the exception of R117M which is more sensitive to autolysis.

Amino Acid Substitution↗
PubMed1998

RGD-containing trypsin with both platelet aggregation inhibitory activity and proteolytic activity.

Arg-Gly-Asp (RGD) motif mediates cell adhesion as a major determinant in interactions of disintegrins with cell surface receptors. In order to obtain a mutant trypsin with both high affinity to integrins and retained proteolytic activity, RGDS and RGD were inserted into a rigid turn region and a flexible loop of trypsin, respectively. Wild type trypsin and substituted mutant trypsins, 37RGDS and 77RGD, were expressed in E. coli and purified. Kinetic properties, autolytic stability as well as platelet aggregation inhibitory activity of both 37RGDS and 77RGD were determined. 37RGDS and 77RGD give retained proteolytic activities of 34% and 87%, respectively, and both become less stable to autolysis. 37RGDS shows an obvious inhibition rate of 29% for platelet aggregation and 77RGD gives a rather weak rate of 14% at the same protein concentration of 3.5 microM, while the wild type trypsin shows no inhibitory activity.

Escherichia coli↗
PubMed1998

Antibody feedback and somatic mutation in B cells: regulation of mutation by immune complexes with IgG antibody.

In response to an appropriate antigenic stimulus, and with help from T lymphocytes, naive B cells differentiate into plasmacytes which produce the primary (germline-encoded) IgM and IgG antibody with low affinity for the antigen. The isotype switch from IgM to IgG coincides with the burst of germinal center reaction and the onset of somatic hypermutation. Here we propose that formation of immune complexes between the residual antigen and the primary IgG antibody, which activate complement and localize specifically in the network of follicular dendritic cells, provides an important signal for triggering the mutation mechanism in germinal center B cells. This hypothesis has been supported by studies on immunogenicity of immune complexes in vivo. The experiments have included an immunization with pre-formed antigen/IgG antibody complex and/or an administration of IgG antibody shortly after the antigen injection. Either of these strategies, which are known to augment the germinal center formation, resulted in earlier onset of somatic mutation and increased mutation frequency in VDJ rearrangements in antigen-reactive B cells, provided that help from T cells was also present. It is presumed that the antigen/antibody/complement complex is able to deliver this important signal by cross-linking of antigen receptor with the CD21/CD19/CD81 molecules on B cells. As a corollary, the signaling by immune complexes may lower the threshold of cell activation determined by receptor affinity for antigen and stimulate diverse V-gene repertoire of B-cell clones in germinal centers.

Animals↗
PubMed1997

Immunization with immune complex alters the repertoire of antigen-reactive B cells in the germinal centers.

The differentiation of memory B cells in germinal centers (GC) is selectively enhanced upon administration of antigen-antibody complexes. To characterize the repertoire of this response, we examined the rearranged immunoglobulin heavy chain variable (V(H)) genes from mouse splenic GC after a single immunization with either antigen, nitrophenyl (NP) hapten coupled to keyhole limpet hemocyanin, or with a preformed complex of antigen with a monoclonal anti-NP antibody of gamma1 isotype. Among antigen-immunized mice, NP-reactive GC B cell populations in the antigen-induced GC consisted mostly of cells expressing the canonical V186.2 gene which contained, on average, 0.8 point mutations/V(H) gene by day 8 after immunization. These results are indicative of the beginning of somatic hypermutation and consistent with previously published analyses of NP antigen-driven GC. In contrast, the NP-specific B cells in GC that were elicited by administration of immune complex represented a heterogeneous cell population expressing nine different germ-line segments of the V186.2/V3 (J558) gene family, i.e. V23, V24.8, C1H4, V3, CH10, V165.1, V102, V671.5 and V186.2. Moreover, the average frequency of mutations in these genes was 1.7, reaching up to 4 mutations/V(H) in some GC. Administration of the antigen NP in complex with specific antibody apparently alters the process of interclonal competition in the GC and results in loss of dominance by V186.2+ cells and nearly stochastic representation of diverse clonotypes. These results suggest an important feedback regulation of the B cell repertoire by antibody and indicate a role for immune complexes in the activation of somatic hypermutation.

Animals↗
PubMedDate not supplied

Multilineage differentiation of ectomesenchymal cells isolated from the first branchial arch.

Cranial neural crest-derived ectomesenchymal cells may be pluripotent stem cells that are capable of generating a range of phenotypes. The fate of these cells appears to be determined in part by intrinsic genetic programs and also by the influence of extracellular signals in the local environment. The extent of lineage determination once neural crest cells have migrated to the first branchial arch is not clear, although branchial arch pattern is not thought to be the result of crest predetermination. The aim of the present study was to test the hypothesis that ectomesenchymal cells of the first branchial arch show properties of pluripotent stem cells, the lineage of which may be directed by specific molecular signaling. Ectomesenchymal cells were enzymatically isolated from the mandibular processes of BALB/c mice and maintained in an undifferentiated state while cultured with leukemia inhibitory factor or induced to differentiate by lineage-specific induction factors or growth conditions, including transforming growth factor beta, forskolin, and a mineralization-promoting medium. Morphological observations and immunocytochemistry demonstrated that cells could be induced to differentiate into smooth muscle cells, glial cells, and osteoblasts, respectively. In the presence of the mineralization-promoting medium, alkaline phosphatase activity increased significantly and mineralization nodules formed. The data reported support the concept that many, although not all, first branchial arch-derived ectomesenchymal cells show properties of multipotent stem cells, the subsequent fate of which can be influenced by induction factors and growth conditions. Some cells, however, showed a degree of commitment with respect to their fate. The possible application of first branchial arch-derived stem cells to tissue engineering of the orofacial tissues should involve consideration of the developmental stage of cell harvesting and the desired cell fate.

Animals↗