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Biomedical subjects

Nan Zhang

Publications and source records attributed to Nan Zhang.

At least 73 records · Page 4Linked to original sources
PubMed2003

[Gamma knife radiosurgery for trigeminal schwannomas].

OBJECTIVE: To evaluate the role of gamma knife (GK) in the treatment of trigeminal schwannomas. METHODS: From June 1994 to June 2000, 38 patients with trigeminal schwannoma treated with GK radiosurgery were reviewed. GK was the primary treatment modality in 30 cases and followed microsurgery in 8 cases. Of the 38 tumors, 12 had small cysts within the tumors, the rest were solid. The mean diameter of the 38 tumors was 32 mm (range: 16 approximately 48 mm) and the tumors ranged in volume from 2 to 33 cm(3) (with a mean mean volume of 9 cm(3)). The maximum dose irradiated to tumor was 20 to 33 Gy (mean: 26 Gy), the tumor margin dose ranged from 11 to 15 Gy (mean: 13 Gy). RESULTS: 35 patients had been followed for 26 to 98 months (mean: 65 months). 20 had been followed more than 60 months. Mild numbness or diplopia relieved completely in 12 patients after GK treatment. Improvement of neurological deficits was seen in 11, unchanged dysfunction or slightly worsening of trigeminal nerve deficits in 9. Three patients had mild worsened symptoms at different time because of tumor progression. Tumor growth control: tumor disappeared after GK treatment was observed in 5 cases from 18 to 36 months after, a marked decrease in volume was observed in 24 cases, unchange in 2 cases and increase in 3 cases at 5, 26, and 60 months after respectively. One patient with resolved symptom refused to have MRI examination for more than 6 years. Of the three increased tumors, one recurrent malignant schwannoma elapsed 26 months after GK treatment. The second was a small tumor and started to progress 5 years after, but after second GK treatment, the tumor decreased again. The third was large tumor and was subtotally removed through surgery because of tumor swelling 5 months after. At last follow-up, the residual tumor remained stable. The control rate of the 35 tumors was 91% (32/35). CONCLUSION: Small and middle-size trigeminal schwannomas are the best candidates for GK radiosurgery. The control dose is 13 to 14 Gy.

Adolescent↗
PubMed2003

Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade.

4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-6,7-diethoxy-3-quinolinecarbonitrile (3) was identified as a MEK1 kinase inhibitor with exceptional activity against LoVo cells. The structure-activity relationships of the C-4 aniline substituents were explored, and water-solubilizing groups were added at the C-7 position to improve physical properties. Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade.

Animals↗
PubMed2003

Topological structure analysis of the protein-protein interaction network in budding yeast.

Interaction detection methods have led to the discovery of thousands of interactions between proteins, and discerning relevance within large-scale data sets is important to present-day biology. Here, a spectral method derived from graph theory was introduced to uncover hidden topological structures (i.e. quasi-cliques and quasi-bipartites) of complicated protein-protein interaction networks. Our analyses suggest that these hidden topological structures consist of biologically relevant functional groups. This result motivates a new method to predict the function of uncharacterized proteins based on the classification of known proteins within topological structures. Using this spectral analysis method, 48 quasi-cliques and six quasi-bipartites were isolated from a network involving 11,855 interactions among 2617 proteins in budding yeast, and 76 uncharacterized proteins were assigned functions.

Algorithms↗
PubMed2003

Feline immunodeficiency virus-mediated viral interleukin-10 gene transfer prolongs non-vascularized cardiac allograft survival.

Previous experiments demonstrated plasmid-, retroviral-, or adenoviral-mediated vIL-10 gene transfer could prolong allograft survival, but transgene expression was rapidly extinguished. Feline immunodeficiency virus (FIV) can integrate into genomic DNA of nondividing cells, resulting in indefinite transgene expression. We hypothesized FIV-mediated gene transfer could provide long-term gene expression, and improved allograft survival. FIV-vIL-10 and FIV-beta-gal were produced using the FELIX vector system. With vector transfer to syngeneic cardiac grafts, beta-galactosidase reporter gene expression was noted as early as day 5, was strongly expressed at days 10 and 20, and persisted for 50 days after transplantation. For allografts, FIV-vIL-10 gene transfer more than doubled mean survival from 10 +/- 1.6 to 22.3 +/- 3 days. When combined with other immunosuppressants, such as anti-CD40L mAb, FTY720, or anti-CD3 mAb, the mean survival times were prolonged to 27 +/- 4.6 days, 27.8 +/- 4.6 days, and 45.5 +/- 4.9 days, respectively. Multiple chemokine and chemokine receptor genes were induced by ischemia-reperfusion injury in syngeneic grafts, and in allogeneic grafts more genes were induced and to a greater degree. In allogeneic grafts transduced with FIV-IL-10, a number of the chemokine genes were suppressed. Therefore, FIV virus-mediated vIL-10 gene transfer prolongs allograft survival and, in combination with other agents, produces an additive effect.

Adenoviridae↗
PubMed2003

Viral IL-10 gene transfer inhibits the expression of multiple chemokine and chemokine receptor genes induced by inflammatory or adaptive immune stimuli.

Previously we have shown that adenovirus-mediated gene transfer and expression of vIL-10 are able to prolong cardiac allograft survival, through the inhibition of the immune response to both alloantigen and adenoviral antigens. In the current study, we have defined further mechanisms of Ad.vIL-10-mediated prolongation of cardiac allograft survival. E1- and E3-deleted adenoviral vectors encoding beta-galactosidase or vIL-10 were transferred into grafts at the time of transplantation, chemokine and chemokine receptor expression were evaluated by a pathway-specific cDNA array, and the results were confirmed with real time RT-PCR on selected genes. Ischemic injury, alloantigen and adenovirus vector induced the expression of multiple pro-inflammatory chemokines in the grafts, which likely amplify allograft rejection. Most of these Th1-related chemokine genes were inhibited or down-regulated by Ad.vIL-10 administration, which may help to decrease leukocytic infiltration and improve graft survival. Among the potent Th1 type chemokines inhibited were the CXCR3 ligands CXCL9 and CXCL10, which could directly inhibit vector-mediated gene expression in myoblasts, although targeting CXCR3 or its ligands did not prolong allograft survival with vIL-10 gene transfer. Ad.vIL-10 administration also induced the expression of the Th2-associated chemokines eotaxin-2 and MIP-1 gamma, suggesting Th1 to Th2 immune deviation. These results demonstrated that the vIL-10 gene transfer inhibits chemokine expression, preventing stimulation of innate and adaptive immunity.

Animals↗
PubMed2003

Differential chemokine and chemokine receptor gene induction by ischemia, alloantigen, and gene transfer in cardiac grafts.

Transplantation of allogeneic grafts presents several challenges to the innate and adaptive immune systems including chemokine leukocyte recruitment, activation, and effector function. We defined the chemokines and receptors induced by the transplant procedure/ischemia injury, alloantigen and gene transfer vector administration in murine cardiac grafts. E1, E3 deleted AdRSVbetagal was transferred into grafts at the time of transplantation, grafts were harvested after 1-14 days, and a pathway-specific cDNA array was used to evaluate the levels of 67 chemokine and chemokine receptor genes. Transplantation resulted in ischemic injury and induction of a number of similar genes in both the syngeneic and allogeneic grafts, such as CXCL1 and CXCL5, which increased dramatically on day 1 and returned rapidly to baseline in the syngeneic grafts. Alloantigen stimulated the adaptive immune response and induced the presence of more inflammatory genes within the grafts, particularly at later time points. The adenovirus vector induced a broader panel of genes, among them potent inflammatory chemokines CXCL9 and CXCL10, that are induced earlier or more strongly compared with alloantigen stimulation alone. As alloantigen and adenovirus vectors both induce similar sets of genes, targeting these molecules may not only inhibit alloimmunity, but also enhance the utility of the gene transfer vector.

Adenoviridae↗
PubMed2003

Adenovirus transduction induces expression of multiple chemokines and chemokine receptors in murine beta cells and pancreatic islets.

Adenoviral vectors are highly efficient for transferring genes to islets. However, the inflammatory and immune responses stimulated by adenovirus may be detrimental to islet survival. Given the role of chemokines and their receptors in inflammation, we analyzed their expression in isolated murine islets, in a murine beta cell line and in syngeneic islet grafts after adenovirus transduction (AdRSVLacZ). AdRSVLacZ transduction enhanced and induced the expression of a variety of chemokines. Transduced syngeneic transplanted islets showed significantly enhanced expression of multiple chemokines and receptors, including monocyte chemoattractant protein-1 (MCP-1), CC chemokine receptor 2 (CCR2) and regulated upon activation, normal T cell expressed and secreted (RANTES), compared with untransduced islet grafts. AdRSVLacZ-transduced islet grafts had significant mononuclear infiltrates, and in situ hybridization demonstrated intragraft expression of MCP-1, CCR2 and RANTES. Although adenovirus transduction did not impair in vitro insulin secretion, diabetes was reversed in only one of six recipients of a marginal mass of AdRSVLacZ-transduced islets, compared with six of six control recipients. In conclusion, multiple chemokines and chemokine receptors are expressed by murine islets constitutively and in response to adenovirus transduction. Adenovirus transduction impairs engraftment of marginal mass of transplanted islets. This is not because of direct vector toxicity of islet secretory capacity, but may be related to host innate immunity in response to adenovirus vector.

Adenoviridae↗
PubMed2003

[Gamma knife radiosurgery for hemangioblastomas: clinical results and pathological findings].

OBJECTIVE: To retrospectively evaluate the effects of Gamma knife in the treatment of cerebral hemangioblastomas. METHODS: From 1993 to 1996, seventeen patients with 29 hemangioblastomas were treated with Gamma knife. The patients mean age was 35 years (range: 16 - 61 years). The mean tumor diameter was 16 mm (range: 6 - 55 mm). Thirteen patients had recurrent or residual hemangioblastomas. Four with primary hemangioblastomas were diagnosed using CT, MRI and DSA. The maximum dose to the tumors was 21.0 - 50.0 Gy, with mean dose of 33.7 Gy. The radiation dose to the periphery of tumors was 12.0 - 24.0 Gy, with mean dose of 17.6 Gy. RESULTS: All the patients had been followed up for 18 to 62 months, with mean 46 months. Five patients experienced clinical improvement and reduction in tumor volume, and 5 remained stable and tumor unchanged in volume during the follow-up period. Three patients died of tumor progression, surgery and cancer after treatment 18, 22, 25 months respectively. Four patients underwent surgery respectively at 3, 4, 29 and 48 months after gamma knife operation. The local control rate of the tumors at 1 year was 92%, 2 years 88%, 3 years 80% and 4 years 75%. Pathological findings in these patients showed varying degrees of small vessel thickening and occlusion together with degeneration, necrosis in the center of tumor and loss of tumor cells at periphery. CONCLUSIONS: Gamma knife is not adequately reliable for the control of hemangioblastoma cysts, it is an effective treatment of small or medium-size solid tumors, but long-term follow-up is needed. The recommended dose is 16 to 20 Gy.

Adolescent↗
PubMed2003

Stereotactic radiosurgery in the treatment of primary central nervous system lymphoma.

OBJECTIVE: To explore the therapeutic alternatives and evaluate the related clinical results of patients with primary central nervous system lymphoma (PCNSL) treated with gamma knife radiosurgery (GKS). METHODS: From January 1995 to December 2001, 44 patients suffering from PCNSL, who had undergone stereotactic biopsy or craniotomy, and who had received a confirmed diagnosis through pathological examination, were treated with GKS. All cases were followed up for 1 - 46 months with an average postoperative period of 27 months. The clinical materials, image features, treatment methods and results of follow-up, were retrospectively reviewed. RESULTS: The symptoms and signs of the patients were markedly improved within 1 - 3 weeks after GKS. The Kanofsky performance status was also improved from a preoperative average of 40% to a postoperative one of 90%. Thirty-eight patients (86.36%) were in complete remission (CR), the other six (13.63%) were in partial remission (PR). The local control rate reached 100%, and the median survival time was 26.5 months. The main side effect was brain edema, which can be treated with dexamethasone and mannitol. CONCLUSION: GKS is a safe and effective method in multimodality treatment of PCNSL. A stereotactic biopsy coupled with GKS is the first choice for diagnosis and treatment. Adjuvant chemotherapy or radiotherapy should then be given according to the patient's condition.

Adult↗
PubMed2003

Treatment of six cases of left renal nutcracker phenomenon: surgery and endografting.

OBJECTIVE: A retrospective study was undertaken to examine therapeutic strategies used in 6 patients with left renal venal nutcracker phenomenon. METHODS: Three patients underwent surgical transposition of the superior mesenteric artery. Three patients underwent endograft stent implantations with intervention. RESULTS: All 6 cases were completely relieved of left renal vein compression after the operations, leading to improved clinical symptoms and normal urine tests. CONCLUSIONS: Transposition of the superior mesenteric artery is a feasible method, but leads to complications and great trauma. Treating left renal venal nutcracker phenomenon with endografting techniques is minimally invasive in certain cases, and seems to have a prospective future.

Adolescent↗
PubMed2002

Regulation of structural plasticity by different channel types in rod and cone photoreceptors.

In response to retinal disease and injury, the axon terminals of rod photoreceptors demonstrate dramatic structural plasticity, including axonal retraction, neurite extension, and the development of presynaptic varicosities. Cone cell terminals, however, are relatively inactive. Similar events are observed in primary cultures of salamander photoreceptors. To investigate the mechanisms underlying these disparate presynaptic responses, antagonists to voltage-gated L-type and cGMP-gated channels, known to be present on rod and cone cell terminals, respectively, were used to block calcium influx during critical periods of plasticity in vitro. In rod cells, L-type channel antagonists nicardipine and verapamil inhibited not only the outgrowth of processes and the formation of varicosities, but also the synthesis of vesicle proteins, SV2 and synaptophysin. In contrast, the synthesis of opsin in rod cells was unaffected. In cone cells, L-type channel antagonists caused only modest changes. However, cobalt bromide, which blocks all calcium channels, and l-cis-diltiazem, a potent antagonist of cGMP-gated channels, significantly inhibited varicosity formation and synthesis of SV2 in cone cells. Moreover, the cGMP-gated channel agonist 8-bromo-cGMP caused a significant increase in varicosity formation by cone but not rod cells. Thus voltage-gated L-type channels in rod cells and cGMP-gated channels in cone cells are the primary calcium channels required for structural plasticity and the accompanying upregulation of synaptic vesicle synthesis. The differing responses of rod and cone terminals to injury and disease may be determined by these differences in the regulation of Ca2+ influx.

Ambystoma↗
PubMed2002

Inhibition of Src kinase activity by 4-anilino-7-thienyl-3-quinolinecarbonitriles.

Based on a screening lead from a yeast-based assay to identify Src family kinase inhibitors, a series of 4-anilino-7-thienyl-3-quinolinecarbonitriles was prepared. When the thiophene ring was substituted with a water-solubilizing group in a 2,5-, 3,5- or 2,4-pattern, potent inhibition of Src kinase activity was observed.

Aniline Compounds↗
PubMed2002

mdmx is a negative regulator of p53 activity in vivo.

Regulation of p53 protein activity is required for normal embryogenesis, tumor suppression, and cellular response to DNA damage. Here we report that loss of mdmx, a p53-binding protein, results in midgestational embryo lethality, a phenotype that is completely rescued by the absence of p53. Mice homozygous for both mdmx and p53 null mutations are viable and appear developmentally normal. Fibroblasts derived from embryos with reduced mdmx expression demonstrate a decreased growth rate and increased UV-induced apoptosis compared with wild-type cells and contain elevated levels of p53 and several p53 target proteins including the proapoptotic bax protein. These observations demonstrate that mdmx functions as a critical negative regulator of p53 in vivo.

Animals↗
PubMed2002

Ammonium dodecyl sulfate as an alternative to sodium dodecyl sulfate for protein sample preparation with improved performance in MALDI mass spectrometry.

Sodium dodecyl sulfate (SDS) is a strong surfactant that is widely used in protein sample preparation. While protein and peptide samples containing up to approximately 1% SDS can be analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) using a two-layer matrix/sample deposition method, the presence of SDS in a protein sample generally degrades mass resolution and mass measurement accuracy. This degradation in performance is found to be related to the formation of sodium-protein adducts in the MALDI process. If the instrument resolving power is insufficient to separate these adduct peaks from the protonated molecular ion peak, peak broadening is observed in the protein molecular ion region, and as a result, the peak centroid shifts to a higher mass. In this work, we present a method using ammonium dodecyl sulfate as a viable alternative to SDS for protein sample preparation with much improved MALDI MS performance. Three non-sodium-based dodecyl sulfate surfactants, ammonium dodecyl sulfate (ADS), hydrogen dodecyl sulfate, and tris(hydroxymethyl)aminomethane dodecyl sulfate were investigated. Of the three surfactants tested, it is found that ADS gives the best performance in MALDI. For proteins with moderate molecular masses (i.e., up to approximately 25 kDa), the presence of ADS in a protein sample does not result in significant degradation in mass resolution and accuracy, and the protonated molecular ion peak is the dominant peak in the MALDI spectrum. The ammonium adduct ions dominate the MALDI spectra when the protein mass exceeds approximately 25 kDa; however, ADS still gives better results than SDS. The behavior of ADS in gel electrophoresis was also investigated. It is shown that cell extracts dissolved in ADS can be separated by normal SDS-polyacrylamide gel electrophoresis by simply mixing them with the SDS sample buffer. The application of ADS as the surfactant for protein solubilization with improved performance in MALDI analysis is demonstrated in the study of a detergent insoluble fraction from a Raji/CD9 B-cell lymphocyte lysate.

B-Lymphocytes↗
PubMed2002

Novel C-C bond cleavage under mild, neutral conditions: conversion of electron-deficient aryl alkyl ketones to aryl carboxylic esters.

A novel, unique way to cleave the carbon-carbon bond in aryl alkyl ketones under mild, neutral conditions is described. Treatment of aryl alkyl ketones in a refluxing mixture of N,N-dimethylformamide dimethyl acetal and methanol for 16 h provided aryl carboxylic esters. The scope and limitations of the reaction are discussed. Useful yields of the reaction can be obtained with electron-deficient aryl groups, and the yields are higher when the alkyl group is larger than a methyl group. Studies toward elucidation of the reaction mechanism led to a proposed mechanism that is consistent with all the observations.

Journal Article↗
PubMed2002

4-Anilino-3-cyanobenzo[g]quinolines as kinase inhibitors.

A series of 4-anilino-3-cyanobenzo[g]quinolines was prepared as potent kinase inhibitors. Compared with their bicyclic 4-anilino-3-cyanoquinoline analogues, the tricyclic 4-anilino-3-cyanobenzo[g]quinolines are less active against EGF-R kinase, equally active against MAPK kinase (MEK), and more active against Src kinase. For Src kinase inhibition, the best activity is obtained when both the 7- and 8-positions are substituted with alkoxy groups. Several of these kinase inhibitors show potent growth inhibitory activity in tumor cells.

Cell Division↗
PubMed2002

Pleiotrophin: a cytokine with diverse functions and a novel signaling pathway.

Pleiotrophin (PTN the protein, Ptn the gene) is a 136 amino acid secreted heparin-binding cytokine that signals diverse functions, including lineage-specific differentiation of glial progenitor cells, neurite outgrowth, and angiogenesis. Pleiotrophin gene expression is found in cells in early differentiation during different development periods and upregulated in cells with an early differentiation phenotype in wound repair. The Ptn gene is a protooncogene. It is strongly expressed in different human tumor cells and expression of the Ptn gene in tumor cells in vivo accelerates growth and stimulates tumor angiogenesis. Separate independent domains have been identified in PTN to signal transformation and tumor angiogenesis. Pleiotrophin is the first ligand of any of the known transmembrane tyrosine phosphatases. Pleiotrophin inactivates the receptor protein tyrosine phosphatase (RPTP) beta/zeta. The interaction of PTN and RPTP beta/zeta increases steady-state tyrosine phosphorylation of beta-catenin. Pleiotrophin thus regulates both normal cell functions and different pathological conditions at many levels. It signals these functions through a transmembrane tyrosine phosphatase.

Amino Acid Sequence↗