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Liang Xu

Publications and source records attributed to Liang Xu.

83 records · Page 5Linked to original sources
PubMed2003

[The role of superantigen SEB-induced immunotolerance in the immune privileged site].

AIM: To investigate if the immunological tolerance induced by superantigen staphylococcus enterotoxin B (SEB) takes part in the reaction at the immune privileged site. METHODS: Corneal transplantations were carried out using LEW rats as recipient and F344 rats as the donor. The recipient rats were randomly divided into 5 groups, receiving peribulbar SEB injection of a dosage of 30, 60, 90 or 120 microg/kg 7 days before and after operations. The negative control group received saline injection while the positive control group received glucocorticoid(GC), FK506, CsA or interleukin-1 receptor antagon ist (IL-1ra), respectively. The survival time and rejection index of corneal grafts within 30 days postoperation were examined and recorded using anti-rejection index method. The inflammatory cell infiltration of the recipient cornea and changes of local NK cells were examined by PE-conjugated anti-NK1.1 monoclonal antibody. RESULTS: The grafts in the group receiving injection of 120 microg/kg SEB survived 22 days longer than the negative control group. Their survival time is also significantly longer than the groups treated with FK506, CsA, GC or IL-1ra. The graft rejection index was 3.42+/-2.18 in the rats receiving 120 microg SEB/kg,but 6.58+/-3.15 in the negative control group (P<0.01). The edema and new blood vessel indexes were also significantly reduced. The immunostaining showed that the number of NK cells increased following injection of SEB. CONCLUSION: Injection of SEB reduced the rejection to corneal transplants in rats, showing that the immune tolerance induced by superantigen SEB plays a role in the reaction at the immune privileged site.

Animals↗
PubMed2002

[Dexamethasone regulate the neuropeptide expression in rabbit's brain injury induced by endotoxin].

OBJECTIVE: To investigate whether dexamethasone (DXM) regulate the expression of Calcitonin gene-related peptide (CGRP), Endothelin (ET), Atrial natriuretic peptide (ANP), Angiotensin II (AII) in brain injury induced by endotoxin in rabbit. METHODS: Sixty-five New Zealand white rabbits were randomly divided into 3 subgroups: endotoxin group (A group), endotoxin + DXM group (B group) and normal saline group (C group). 100 microg/kg endotoxin was intracerebroventricularly injected in A group, endotoxin 100 microg/kg + DXM 1 mg/kg in B group and same volume of normal saline in C group as control. Neuropeptide level were detected by radioimmunoassay in variable periods (3 h, 6 h, 12 h, 24 h, 48 h, 72 h after injection) in the plasma, cerebrospinal fluid (CSF) and brain tissue (hippocampus area), and brain water content was measured by dry method. RESULTS: CGRP, ET, ANP, AII concentrations in plasma, CSF and brain tissue changed in variable periods after injection. The higher or the lower neuropeptide levels were emerged on 12 - 24 hours after injection (P < 0.05 or P < 0.01), and changed remarkably in A group (P < 0.05 or P < 0.01). Brain water content were significantly higher and reached to peak level on 24 hours after injection. But there was a significantly increasing in A group compared to that of B group (P < 0.05 or P < 0.01). CONCLUSIONS: The timely changes of CGRP, ET, ANP, AII were related to brain injury and brain edema induced by endotoxin, and DXM regulated the expression of neuropeptides and lighten brain edema.

Angiotensin II↗
PubMed2002

[Incidence of senile dementia and depression in elderly population in Xicheng District, Beijing, an epidemiologic study].

OBJECTIVE: To investigate the incidence of senile dementia and depression in the elderly and the factors correlative with these disorders. METHODS: All the non-case subjects investigated in a survey of prevalence of senile dementia and depression conducted among the elderly population in Xicheng District, Beijing in 1997 were followed up in 1999. The investigation procedure, instruments and diagnostic criteria were identical with those used in 1997 survey. RESULTS: The annual incidence rates of senile dementia was 0.89% in those aged 60 and over. The incidence rate of old males and that of the old females were not significantly different. The annual incidence rate of senile dementia in groups aged 60 approximately 64, 64 approximately 69, 70 approximately 74 75 approximately 79 80 approximately 84 85 approximately 89, and 90 and over were 0.15% 0.68 % 0.44% 1.32% 2.41% 5.72% and 5.13% respectively. The incidence rate in the elderly over 90 was lower than that in the group aged 85 approximately 89. The minimum annual incidence rate of depression in the elderly aged 60 and over was 1.28%. The incidence rate of depression was higher in the group with poorer health than in the group with better health. The incidence rates of moderate and severe dementia were not significantly different from those in 1989. CONCLUSION: The incidence rate of senile dementia in the elderly remains rather stable during this period of 10 years in Beijing city. The incidence rate of senile dementia is closely correlated with age. The incidence rate of depression in the elderly is remarkably correlated with health status. Senile dementia and depression may coexist in the same person.

Aged↗
PubMed2002

Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery.

Molecular therapy, including gene therapy, is a promising strategy for the treatment of human disease. However, delivery of molecular therapeutics efficiently and specifically to the target tissue remains a significant challenge. A human transferrin (Tf)-targeted cationic liposome-DNA complex, Tf-lipoplex, has shown high gene transfer efficiency and efficacy with human head and neck cancer in vitro and in vivo (Xu, L., Pirollo, K.F., Tang, W.H., Rait, A., and Chang, E.H. Hum. Gene Ther. 1999;10:2941-2952). Here we explore the structure, size, formation process, and structure-function relationships of Tf-lipoplex. We have observed Tf-lipoplex to have a highly compact structure, with a relatively uniform size of 50-90 nm. This nanostructure is novel in that it resembles a virus particle with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. More importantly, compared with unliganded lipoplex, Tf-lipoplex shows enhanced stability, improved in vivo gene transfer efficiency, and long-term efficacy for systemic p53 gene therapy of human prostate cancer when used in combination with conventional radiotherapy. On the basis of our observations, we propose a multistep self-assembly process and Tf-facilitated DNA cocondensation model that may provide an explanation for the resultant small size and effectiveness of our nanostructural Tf-lipoplex system.

Animals↗
PubMed2002

Upstream binding factor up-regulated in hepatocellular carcinoma is related to the survival and cisplatin-sensitivity of cancer cells.

Upstream binding factor (UBF) is an RNA polymerase I-specific transcription factor. By representational difference analysis, Northern blot, and cDNA array analysis, up-regulation of UBF was detected in 12 of 17 clinical hepatocellular carcinoma samples comparing to the paired normal liver tissues. Introduction of UBF in human lung fibroblast cells that do not express UBF resulted in an accelerated rate of cell growth; on the other hand, antisense oligodeoxynucleotides (ODNs) treatment of UBF-expressing hepatoma cell lines reduced the level of UBF protein, suppressed the colony formation capacity of these cells on soft agarose, and finally caused cell death. Annexin V binding analysis suggested that anti-UBF ODN-caused cell death might involve weak apoptosis, however, DNA laddering and cleavage of poly (ADP-ribose) polymerase were not observed in these ODN-treated cells. Expression profiling of the anti-UBF ODN-treated cells using a human cDNA array revealed that the expression of 30 genes was altered in response to the inhibition of UBF expression. Notably, UBF expression could increase the cell sensitivity to the chemotherapeutic reagent cis-diaminedichloroplatinum (II). We proposed that UBF is fundamental to the survival of cells expressing the gene, and is potential as a target for screening anti-cancer drugs and an indicator in selecting chemotherapeutic reagents.

Antineoplastic Agents↗
PubMed2002

Hepatic DR5 induces apoptosis and limits adenovirus gene therapy product expression in the liver.

A major limitation of adenovirus (Ad) gene therapy product expression in the liver is subsequent elimination of the hepatocytes expressing the gene therapy product. This elimination is caused by both necrosis and apoptosis related to the innate and cell-mediated immune response to the Ad. Apoptosis of hepatocytes can be induced by the innate immune response by signaling through death domain receptors on hepatocytes including the tumor necrosis factor alpha (TNF-alpha) receptor (TNFR), Fas, and death domain receptors DR4 and DR5. We have previously shown that blocking signaling through TNFR enhances and prolongs gene therapy product expression in the liver. In the present study, we constructed an Ad that produces a soluble DR5-Fc (AdsDR5), which is capable of neutralizing TNF-related apoptosis-inducing ligand (TRAIL). AdsDR5 prevents TRAIL-mediated apoptosis of CD3-activated T cells and decreases hepatocyte apoptosis after AdCMVLacZ administration and enhances the level and duration of lacZ transgene expression in the liver. In addition to blocking TRAIL and directly inhibiting apoptosis, AdsDR5 decreases production of gamma interferon (IFN-gamma) and TNF-alpha and decreases NK cell activation, all of which limit Ad-mediated transgene expression in the liver. These results indicate that (i) AdsDR5 produces a DR5-Fc capable of neutralizing TRAIL, (ii) AdsDR5 can reduce activation of NK cells and reduce induction of IFN-gamma and TNF-alpha after Ad administration, and (iii) administration of AdsDR5 can enhance Ad gene therapy in the liver.

Adenoviruses, Human↗
PubMed2002

[A morphological study of neuroretinal rim for different types of optic disc in normal eyes and early glaucoma].

OBJECTIVE: To investigate the morphological characteristics of neuroretinal rim in different types of the normal optic disc and early glaucoma. METHODS: The subjects were divided into four groups: (1) 41 eyes with physiologic small disc. (2) 40 eyes with physiologic large disc. (3) 42 eyes with normal size disc. (4) 45 eyes with early glaucoma. The optic disc area, neuroretinal rim area, cup area and a circuit (each 10( degrees ) neuroretinal rim widths were measured by using computerized imaging system. The curve of sequential neuroretinal rim widths was made from temporal to superior, nasal, and inferior. RESULTS: (1) The morphological characteristic of the curve of sequential rim widths in normal eyes was that there were double humps in inferior and superior section, double valley in nasal and temporal section. (2) The loss of double humps of inferior and superior section was at the curve of sequential rim widths in early glaucoma. It was lower than nasal and higher than temporal section. (3) The inferior rim width of the physiologic large disc was the widest, while the superior rim width was the widest in the physiologic small disc, followed by the nasal and temporal section. (4) The correct discrimination ratio was 85.7% and 90.6% with rim area plus C/D and sequential neuroretinal rim widths (inferior 6:20 and superior 1:00 neuroretinal rim widths were the most effective) respectively in the multivariate discrimination. CONCLUSION: The nasal neuroretinal rim width itself is regarded as the standard, and compare the superior and inferior with nasal neuroretinal rim width in estimating the morphological characteristics of neuroretinal rim. This way is very effective in discriminating physiologic large optic cup from the cup of early glaucoma.

Glaucoma↗
PubMed2002

Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes.

An ideal therapeutic for cancer would be one that selectively targets to tumor cells, is nontoxic to normal cells, and that could be systemically delivered, thereby reaching metastases as well as primary tumor. Immunoliposomes directed by monoclonal antibody or its fragments are promising vehicles for tumor-targeted drug delivery. However, there is currently very limited data on gene delivery using these vehicles. We have recently described a cationic immunoliposome system directed by a lipid-tagged, single-chain antibody Fv fragment (scFv) against the human transferrin receptor (TfR) that shows promising efficacy for systemic p53 tumor suppressor gene therapy in a human breast cancer metastasis model. However, the extremely low yield of this lipid-tagged scFv limited further downstream development and studies. Here we report a different expression strategy for the anti-TfR scFv, which produces high levels of protein without any tags, and a different approach for complexing the targeting scFv to the liposomes. This approach entails covalently conjugating the scFv to the liposome via a cysteine at the 3'-end of the protein and a maleimide group on the liposome. Our results show that this conjugation does not impair the immunological activity or targeting ability of the scFv. The scFv-cys targets the cationic liposome-DNA complex (lipoplex) to tumor cells and enhances the transfection efficiencies both in vitro and in vivo in a variety of human tumor models. This scFv-immunoliposome can deliver the complexed gene systemically to tumors in vivo, where it is efficiently expressed. In comparison with the whole antibody or transferrin molecule itself, the scFv has a much smaller size for better penetration into solid tumors. It is also a recombinant protein rather than a blood product; thus, large scale production and strict quality control are feasible. This new approach provides a promising system for tumor-targeted gene delivery that may have potential for systemic gene therapy of various human cancers.

DNA↗