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Biomedical subjects

Shaohua Chen

Publications and source records attributed to Shaohua Chen.

9 recordsLinked to original sources

General solution to two-dimensional nonslipping JKR model with a pulling force in an arbitrary direction.

In this paper, a generalized JKR model is investigated, in which an elastic cylinder adhesively contacts with an elastic half space and the contact region is assumed to be perfect bonding. An external pulling force is acted on the cylinder in an arbitrary direction. The contact area changes during the pull-off process, which can be predicted using the dynamic Griffith energy balance criterion as the contact edge shifts. Full coupled solution with an oscillatory singularity is obtained and analyzed by numerical calculations. The effect of Dundurs' parameter on the pull-off process is analyzed, which shows that a nonoscillatory solution can approximate the general one under some conditions, i.e., larger pulling angle (pi/2 is the maximum value), smaller a/R or larger nondimensional parameter value of Deltagamma/E*R. Relations among the contact half width, the external pulling force and the pulling angle are used to determine the pull-off force and pull-off contact half width explicitly. All the results in the present paper as basic solutions are helpful and applicable for experimenters and engineers.

Cell Adhesion↗

Hepatocyte growth factor is a lymphangiogenic factor with an indirect mechanism of action.

Hepatocyte growth factor (HGF) has previously been reported to act as a hemangiogenic factor, as well as a mitogenic factor for a variety of tumor cells. Here, we demonstrate that HGF is a lymphangiogenic factor, which may contribute to lymphatic metastasis when overexpressed in tumors. In a mouse corneal lymphangiogenesis model, implantation of HGF induces sprouting and growth of new lymphatic vessel expressing the lymphatic vessel endothelial specific marker hyaluronan receptor-1 (Lyve-1). Unlike blood vessels, the Lyve-1-positive structures consist of blunt-ended vessels of large diameters that generally lack expression of CD31. The growth of HGF-induced lymphatic vessels can be partially blocked by a soluble VEGFR-3, suggesting that HGF may stimulate lymphatic vessel growth through an indirect mechanism. Consistent with this finding, the HGF receptor (c-Met) is only localized on corneal blood vessels but is absent on lymphatic vessels in a mouse corneal assay. In a transgenic mouse model that expresses HGF under the control of the whey acidic protein (WAP) gene promoter, transgenic females develop tumors in the mammary glands after several pregnancies. Interestingly, dilated Lyve-1-positive lymphatic vessels accumulate in the peritumoral area and occasionally penetrate into the tumor tissue. Our findings indicate that HGF may play a critical role in lymphangiogenesis and potentially contribute to lymphatic metastasis.

Animals↗

IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the CNS initiated by autoreactive CD4(+) T cells. EAE classically presents with a progressive ascending paralysis and is a model of multiple sclerosis that recapitulates some aspects of the disease. In this report we describe a mouse strain that spontaneously develops a severe, nonclassical form of EAE with 100% incidence. The distinct clinical phenotype is marked initially by a slight head tilt, progressing to a severe head tilt, spinning, or a rotatory motion. Classical EAE spontaneously occurs in myelin basic protein (MBP)-specific TCR transgenic RAG-1(-/-) mice (referred to as T/R(-)), whereas nonclassical EAE spontaneously occurs in T/R(-) IFN-gamma(-/-) mice (T/R(-)gamma(-)). Thus, the TCR recognizes the same Ag (MBP) and uses identical TCR in both cases. The cellular infiltrate in nonclassical EAE is predominantly found in the brainstem and cerebellum, with very little inflammation in the spinal cord, which is primarily affected in classical disease. Importantly, depending on the genetic makeup and priming conditions of the MBP-specific T cells, nonclassical disease can occur in the presence of an inflammatory infiltrate with eosinophilic, neutrophilic, or monocytic characteristics. Finally, we believe that nonclassical spontaneous EAE could be a useful model for the study of some characteristics of multiple sclerosis not observed in classical EAE, such as the inflammatory responses in the brainstem and cerebellum that can cause vertigo.

Animals↗

Clonal expanded TCR Vbeta T cells in patients with APL.

T-cell receptor Vss gene repertoire and clonality have been studied in patients with leukemia and solid tumors, by assaying the CDR3 size of TCR genes, using RT-PCR and genescan analysis. Few studies have studied leukemia-associated oligoclonal expanded T-cells in leukemia, therefore, the aim of this study was to investigate the distribution and clonal expansion of T-cell receptor, Vss subfamily T-cells in patients with acute promyelocytic leukemia (APL) with t(15;17). The CDR3 of TCR Vbeta24 subfamily genes were analyzed in peripheral blood mononuclear cells from 17 cases with PML-RARalpha+ APL using RT-PCR and genescan technique. Ten normal individuals served as controls. The results showed that the number of expressed Vss subfamilies (from 2 to 21 subfamilies) varied in different patients with APL. The most frequently expressed Vss subfamilies were Vbeta2 (64.7%), Vbeta15 (58.8%), Vbeta3 and Vbeta5 (47.1%), with a lower expression rate found in Vbeta11 and Vbeta20 (11.7%). Clonally expanded T-cells in the Vss subfamilies could be identified in patients with APL in all but two of the cases studied, predominantly in Vbeta10, Vbeta23, Vbeta3 and Vbeta21. In conclusion, skewed distribution and clonal expansion of TCR Vss subfamily T-cells could be found in patients with APL. The clonal expansion of T-cells were considered to be a specific anti-leukemic immune response by host T-cells activated by the leukemia-associated-antigen.

Adolescent↗

The TCR Vbeta repertoire usage of T-cells from cord blood induced by chronic myelogenous leukemia associated antigen.

Understanding the clonality and restricted usage of the TCR Vbeta repertoire of expanded T-cells induced by the chronic myelogenous leukemia (CML) associated antigen may be useful in helping design new immunotherapeutic strategies specifically for CML. T-cells from cord blood that had been stimulated by different stimulators (IL-2, PHA, CML cells, K562 cells and bcr-abl peptide) were amplified in vitro by liquid T-cell culture and the mixed lymphocyte and tumor cell culture (MLTC) method. By using the RT-PCR, the CDR3 segments of 24 variable region genes of TCR beta was analyzed in T-cells from 22 cases of cord blood before and after T-cell culture, to observe the usage of TCR Vbeta repertoire. The PCR products were further labeled with fluorescence and analyzed by the Genescan technique for the CDR3 size, to evaluating clonality of the detectable TCR Vbeta T-cells. Only a part of 24 Vbeta subfamily T-cells (3-15 subfamilies) could be detected, however, all of the 24 TCR Vbeta subfamily of T-cells were detected after in vitro culture with PHA or IL-2+anti-CD3 antibody. The number of expressed TCR Vbeta subfamilies was gradually reduced by prolonging the time of culture with CML-associated antigens. The restricted expression of TCR Vbeta subfamilies and oligoclonal expansion of Vbeta21 T-cells were found in cultured T-cells induced by CML cells, K562 cells or bcr-abl peptide. In conclusion, T-cells from cord blood may have the potential capability of proliferation in different TCR Vbeta subfamily T-cells, and the ability for restricted expression and clonal expansion, when T-cells were induced by CML associated antigen.

Cell Proliferation↗

Clonal expansion T cells identified in acute monoblastic leukemia by CDR3 size analysis of TCR V beta repertoire using RT-PCR and genescan.

OBJECTIVE: To investigate the distribution and clonality of T cell receptor (TCR) V beta repertoire in patients with acute monoblastic leukemia (AML-M5). METHODS: Expression of the TCR V beta repertoire was analyzed using reverse transcription-polymerase chain reaction (RT-PCR), which amplified the complementarity determining region 3 of 24 TCR V beta genes in peripheral blood from 9 cases with acute myclogenous leukemia subtype 5 or acute monoblastic leukemia (AML-M5). PCR products were further studied by genescan analysis to identify T cell clonality. RESULTS: Expression of 1-10 V beta subfamilies was found in samples from 9 patients. Genescan analysis showed that some V beta subfamily products from 8 of 9 cases contained an oligoclonal peak. Oligoclonal T cells of the V beta 2 subfamily could be found in 6 patients with AML-M5. CONCLUSIONS: T cell clonality expansion was found in AML-M5 cases and were tendentious in the V beta 2 subfamily, suggesting a the specific immune response for leukemia cell (M5) associated antigen and may display antileukemia activity.

Complementarity Determining Regions↗

[The Insertional Mutation of Transcription Factor GATA-2 Gene in Acute Non-Lymphocytic Leukemia]

To investigate the expression and mutation of transcription factor GATA-2 gene in acute non-lymphocytic leukemia (ANLL), the GATA-2 gene were amplified in peripheral blood mononuclear cells from 85 cases with ANLL using RT-PCR, and the PCR products were further analyzed by single strand conformation polymorphism (SSCP) and sequencing. The results showed that GATA-2 gene was expressed in the most cases with ANLL (89.4%). One larger band was observed by RT-PCR in a case with M(1) subtype. Nucleotide sequence analysis revealed a insertion of 18 nucleotides at position 1 288 bp of the GATA-2 gene cDNA, thereby leading to 6 additional amino acids in second zinc finger complex of GATA-2, and it includes a cysteine which can bind to zinc ion. The insertional mutation may change the function of GATA-2 transcription factor. To our knowledge this is the first description of insertional mutation in the GATA-2 gene.

Journal Article↗

[Detection of Human Herpesvirus-6 DNA in Peripheral Blood Cells of Patients with Myelogenous Leukemia by Nested PCR]

Human herpesvirus-6 (HHV-6) is largly disseminated in human population, which may relate to many diseases. Due to different methods previously used, the results of HHV-6 DNA detections in patients with leukemia are not identical. With a control-study, HHV-6 DNA in the blood cells from 38 cases, including 30 cases with acute myeloid leukemia and 8 cases with chronic myelogenous leukemia was detected by nested PCR. The results showed that HHV-6 DNA positive rate (63%) in patients with AML was lower than that in controls, whereas no significant difference between patients with CML (75%) and controls (92%) was shown. The clinical importance of HHV-6 infections in myelogenous leukemia should continue to be investigated later.

Journal Article↗

[The Feature of Skewing Distribution of TCR Vbeta T Cells from Peripheral Blood and Bone Marrow in Patients with AML-M(5)]

The TCR Vbeta 24 subfamily genes were amplified in peripheral blood and bone marrow mononuclear cells from 5 cases with acute monocytic leukemia (AML-M(5)) using RT-PCR, to observe the distribution of TCR Vbeta subfamilies. The results indicated that 1 - 19 Vbeta subfamily T cells could be identified in different samples from AML-M(5) cases. The variation of distribution of TCR Vbeta subfamily T cells could be found in different individual samples. The results provided the feature of cell immune function change in skewed distribution of TCR Vbeta subfamily T cells from peripheral blood and bone marrow of patients with AML-M(5).

Journal Article↗