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Biomedical subjects

Le Xiao

Publications and source records attributed to Le Xiao.

8 recordsLinked to original sources

Survival of adult neurons lacking cholesterol synthesis in vivo.

BACKGROUND: Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. RESULTS: Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. CONCLUSION: We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

Animals↗

Development of quartz-crystal-microbalance-based immunosensor array for clinical immunophenotyping of acute leukemias.

An integrated piezoelectric immunosensor array has been developed to immunophenotype acute leukemias in clinic. Each quartz crystal microbalance (QCM) was fabricated with plasma-polymerized film of n-butylamine, nanogold particles, and protein A (PA) to be used to immobilize antibodies in orientation. Leukemic lineage-associated monoclonal antibodies were separately immobilized onto the nanogold-PA-modified surface of the crystals, which were constructed by a 2 x 2 type of probes forming a QCM-based immunosensor array. The main detection conditions were investigated, including the immobilization amount of antibodies, pH, immunoreaction time, sample dilution ratio, etc. The immunophenotyping feasibility of the new technique was investigated through simultaneously analyzing Jurkat cells by the immunosensor array method, immunohistochemistry, and flow cytometry. It was found that the developed technique could readily identify leukemia samples in 5 min and might monitor dynamically the immunoreaction processes. Moreover, comparison studies were carried out for CD antigens expressed on the nucleated cells isolated from 96 acute leukemic patients and 24 normal subjects using the QCM-based immunosensor method and the fluoroimmunoassay. Results obtained by immunophenotyping patients' samples with the immunosensor-based method achieved the rate of 88.93% in 768 groups of numerical data, where no significant statistical difference was observed between the two methods when checked by chi2 analysis (chi2 = 3.4, p > 0.05). This new immunosensor array showed the merits of high sensitivity, high specificity, good reproducibility, easy operation, and low cost. The results of specimen evaluation indicated that it might be clinically suitable for quantifying human differentiated leukocytes and immunophenotyping of acute leukemias.

Acute Disease↗

[Specific cell immune response mediated by dendritic cells in multiple myeloma patients in vitro].

OBJECTIVE: To explore KM3 multiple myeloma (MM) cell line specific cytotoxic T lymphocyte (CTL) response in vitro mediated by autologous dendritic cells (DCs) aroused by KM3 cells' lysates and acid-eluted peptides. METHODS: Monocytes were isolated from the peripheral blood of healthy individuals and MM patients, and were cultured in serum medium with IL-4, GM-CSF, and TNF-alpha to generate DCs. These DCs were pulsed by KM3 cells' lysates or the acid-eluted peptides, then incubated with autologous T lymphocytes for 3 days to induce KM3 cell antigen specific CTL. MTT assay was performed to examine the specific KM3 cells' lysing ability of CTL. RESULTS: DCs were generated in peripheral blood monocytes cultured in the serum medium containing GM-CSF, IL-4, and TNF-alpha. Autologous T lymphocytes induced by IL-2 and DCs pulsed with KM3 cells' lysates or the acid-eluted peptides showed strong killing effect on KM3 cells. CONCLUSION: The DCs pulsed by KM3 cells' lysates or the acid-eluted peptides incubated with autologous T lymphocytes can induce KM3 cell antigen specific CTL.

Cells, Cultured↗

[Acute monocytic leukemia after orthotopic liver transplantation: clinical features, molecular genetics, and significance thereof].

OBJECTIVE: To study the clinical features and molecular genetics of acute monocytic leukemia (AML) after orthotopic liver transplantation and significance thereof. METHODS: The clinical manifestations, laboratory findings, development, diagnosis, treatment, and prognosis of the first case of AML after orthotopic liver transplantation in the world, a Chinese, male, aged 46, were observed. RT-PCR was used to analyze the mRNA expression of FLT3, Pim-1, and Hsp-70 in the bone marrow mononuclear cells (BMMCs) of the patient. Nucleotide sequence analysis was used to detect the mutation of FLT3-ITD. Flow cytometry was used to examine the protein expression of C-kit, a stem cell factor receptor, and platelet derived growth factor receptor-alpha (PDGFRalpha). RESULTS: (1) Three months after the orthotopic liver transplantation the patient manifested symptoms and signs of anemia and thrombocytopenia. Laboratory tests found increase of white blood cells and myeloblasts with Auer's rods. Cytogenetic analysis showed a genotype of 46XY/47XY with an extra chromosome 8. Bone marrow examination revealed increased promonocytes. The diagnosis of chronic myelomonocytic leukemia was made. Five months after the liver transplantation the disease developed to AML. The patient underwent combined chemotherapy (HA or DA regimens) for 5 courses and showed a partial remission both hematologically and in bone marrow examination at first, however, became resistant to all chemotherapeutic agents. RT-PCR showed absence of wild type FLT3 allele. At last the patient died of infection. (2) A FLT3-ITD mutation of "insertion" type was identified in the BMMCs. The Pim-1 mRNA was weakly expressed and the expression of Hsp-70 mRNA was upregulated in the BMMCs. (3) The protein expression of C-kit and that of PDGFRalpha were both upregulated in the BMMCs as showed by flow cytometry. CONCLUSION: Orthotopic liver transplantation may be complicated with acute leukemia heterogeneous in clinical features and hematology. Certain defects in cytogenetics/molecular genetics may attribute to unfavorable prognosis.

HSP70 Heat-Shock Proteins↗

[Role of pre-coating in artificial vessel endothelialization].

OBJECTIVE: To understand the value of pre-coating in artificial vessel endothelialization. METHODS: Literature concerning pre-coating in artificial vessel endothelialization was extensively reviewed. RESULTS: Pre-coating included chemical coatings (collagen, fibronectin, laminin, poly-l-lysin, gelatin and extracellular matrix), pre-clotting (plasma, blood, serum and fibrin glue), chemical bonding (heparin, RGD and lectins) and surface modification. Most of them could enhance the adhesion of the endothelial cells. CONCLUSION: Pre-coating could improve endothelialization, but further research is needed to search for the appropriate concentration and incubation time.

Animals↗

Role of precoating in artificial vessel endothelialization.

As the progress of vascular surgery, artificial vessels have become the substitute for large and middle diameter vessels but have not for small diameter ones owing to thrombogenesis and occlusion within a short period of time after being applied. Artificial vessel endothelialization is one of the ideal methods to resolve such issue and has been improved continuously since Herring in 1978 put forward this term in the first time and utilized vascular endothelial cells (ECs) harvested from living animals to perform the test of artificial vessel endothelialization. However, human endothelial cells show little adhesion to the currently available vascular graft materials and some expanded polytetrafluoroethylene (ePTFE) grafts have shown only 10%+/-7% endothelial cell attachment rate (ECA, ie, attachment of ECs when incubated in vitro). Moreover, when the graft is exposed to pulsatile blood flow, a high proportion of cells are washed off from the lumen. Maximum cell loss occurs in the first 30-45 min after exposure to pulsatile flow, with up to 70% of cells lost. After that, a slower exponential loss occurs over the next 24 h. The lack of retention of cells could be partly overcome by sodding, but other techniques, involving engineering the lumen to improve ECA and endothelial cell retention rate (ECR, ie, retention of ECs when the grafts are exposed to pulsatile flow) have been developed. These include shear stress preconditioning, electrostatic charging and, above all, most successfully to date, precoating with EC specific adhesive glues that are mostly found in the extracellular basement membrane of blood vessels. The commonest are chemical coatings, preclotting, chemical bonding, and surface modifications.

Blood Vessel Prosthesis↗

[Characteristics and clinical significance of immunophenotype in chronic lymphocytic leukemia].

OBJECTIVE: To investigate the characteristics of immunophenotype of chronic lymphocytic leukemia (CLL) and to evaluate the prognosis of CLL by using the indexs of the characteristics of immunophenotype combined with serum LDH and beta2-MG levels. METHODS: The immunophenotype of 15 CLL, 12 AML, 11 ALL, and 1 FCL (follicular cell lymphoma) patients were analyzed by the indirect immunofluorescent assay. The serum LDH and beta2-MG were detected in 13 CLL patients by the rate nephelometry. RESULTS: The mean age of episode for CLL was 62.9 years and the ratio of male to female was 4:1 in the CLL group. The immune markers (CD5, CD19, and CD20) were positive in the 15 CLL, and negative in the 11 ALL and the 12 AML. The expression of CD23 was positive in 12 of the 15 CLL and negative in the 11 ALL and 12 AML. The expression of CD38 was positive in the 15 CLL. The immunophenotype of 1 FCL was CD10+, CD19+, CD20+, CD5- and CD23-. The serum beta2-MG and LDH levels in 9 CLL patients at Stage Binet C were significantly higher than those in 3 CLL patients at Stage Binet A (P < 0.05). CONCLUSION: CD19+, CD20+ and CD5+ are specific assembly of immunophenotype in B-CLL and contribute to the diagnosis of CLL. The clinical stage of CLL patients of CD23- belongs to Stage Binet C, indicating the poor prognosis. CD23 contributes to differentiate CLL from FCL. CD38+ as a prognostic marker of CLL is not specific. The levels of LDH and beta2-MG are useful indexes for evaluating the prognosis of CLL.

Aged↗