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Biomedical subjects

Ming Zhao

Publications and source records attributed to Ming Zhao.

At least 145 records · Page 8Linked to original sources

[Malignant fibrous histiocytoma of head and neck: clinical analysis of 21 cases].

BACKGROUND & OBJECTIVE: Malignant fibrous histiocytoma (MFH) is a type of pleomorphic neoplastic diseases with complex pathological structure. Its histological origin is uncertain. It was often classified as other carcinoma. This study was designed to investigate the clinical and pathological features and improve the diagnosis and treatment. METHODS: To summarize and analyze the clinical experiences of 21 cases of MFH at head and neck proved histologically from June 1984 to June 1999 treated in Department of Head and Neck Surgery, Henan Tumor Hospital. RESULTS: Twenty cases were followed up more than 3 years; one case was lost. The 3-year survival rate was 42.9%(9/21). Nineteen cases were treated with surgery. Two cases in advanced stage were treated by non-surgery who died in 2 and 5 months. Among the patients treated with surgery, 6 cases survived without evidence of recurrence more than 3 years, 13 cases recurred within 2 years and 9 cases with metastasis. Seven cases received second surgery after recurrence. Among them,3 cases survived more than 3 years after second surgery. Of all 21 patients, 12 were proved with cervical lymph node metastasis. CONCLUSION: MFH at head and neck region is a kind of malignant disease with high recurrent rate and the cervical lymph node metastasis rate was 57.1%. Amplified radical surgery is the first choice of treatment. The second surgery has special value to the recurrent patients. Radiotherapy alone or chemotherapy alone is not effective to MFH of head and neck region.

Adolescent↗

[Rice allelopathy to barnyardgrass].

138 rice (Oryza sativa) germplasms were identified to study the allelopathy to barnyardgrass (Echinochloa crusgalli), using the relay seeding technique. The results showed that Qingkun 2 from Jiangxi Province, Xiayitiao from Jiangsu Province, Jizaoxian from Anhui Province, Ganzaoxian 37 from Jiangxi Province, Shangnuo 1, IR68465-2-3-2 from IRRI, and Shuiyuan 2 from Korea had a strongly excellent inhibition effect on barnyardgrass. Results from pot culture showed that Gumei 2 and Zhong 156 had a greater inhibitory effect than control, and allelopathic material TN1 had no significantly inhibition effect, compared to non-allelopathic material Xiushui 63. The effect of Zhong 156 was related to its plant height, and significant different from that of Xiushui 63. Gumei 2 had a stronger inhibition effect on barnyardgrass, due to its own allelopathic trait.

Echinochloa↗

[Molecular biological study on the action mechanism of rice allelochemicals against weeds].

Rice allelopathy is implemented through its release of allelochemicals to environment. Many researchers considered that rice allelochemicals were phenolics. The action mechanisms of rice against weeds allelochemicals included the inhibition of seed germination and emergence, the effect on the balance of hormones, the damage on the integrity of cell membrane systems, the effect on photosynthesis and respiration, the disturbance of nutrient and water uptake and the effect on the protein synthesis and gene expression. Rice allelopathy is controlled by polygenes, and inherited quantitatively. Several QTLs were identified by the methods of molecular biological techniques and allelopathic bioassay. It might be the important research work to locate the QTLs accurately and to clone the allelopathic genes with the method of marker-assisted selection and the near isogenic lines.

Cloning, Molecular↗

Exploring the origins of cementoblasts and their trigger factors.

Future directions for designing periodontal regenerative therapies hinge on characterization of cells associated with periodontal tissues and on signals instrumental in regulating their behavior. Studies here focused on determining the responsiveness of putative cementoblast progenitor cells (follicle cells), periodontal ligament cells, and cementoblasts to specific factors. Cementoblasts (OCCM), periodontal ligament (SVPDL) cells, and follicle cells (SVF4) were isolated from mouse tissues and immortalized, where SV indicates the use of SV-40 for immortalization. Cultured cells were examined for response to parathyroid hormone-related protein (PTHrP), bone morphogenetic protein-2 (BMP-2), and enamel matrix derivative (EMD) using RT-PCR, Northern analysis, and in vitro and in vivo mineralization assays. Results showed that the three cell lines varied in their expression of bone sialoprotein (BSP) and osteocalcin (OCN), and in their capacity to promote mineralization. RT-PCR indicated that all cell lines had PTH/PTHrP-R1 and BMP receptors; however, the response of individual cell lines to PTHrP, BMP-2, and EMD was quite different. Such dissimilarities in responsiveness associated with cell type may need to be considered when designing regenerative therapies.

Animals↗

[Cytokine gene polymorphism in sensitized kidney transplant recipients and its association with acute rejection episodes].

OBJECTIVE: To investigate the relationship between cytokine gene polymorphism in sensitized kidney transplant recipients and acute rejection episodes. METHODS: PCR using sequence-specific primer (PCR-SSP) was performed to determine the cytokine genotypes of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1), interleukin-6 (IL-6), interferon-gamma (IFN-gamma) in 97 sensitized kidney transplant recipients. The association of cytokine genotypes with early graft rejection was explored. RESULTS: Acute rejection occurred in 23 of the 97 patients during the first three months after operation. The incidence of acute rejection was higher in the recipients with high TNF-alpha or high IL-10 producer genotype (51.9% and 55.5% respectively) than in the recipients with low TNF-alpha or low to intermediate IL-10 producer genotype (12.9% and 13.3% respectively, P<0.01). The incidence of acute rejection was even higher in the recipients with high TNF-alpha in combination with intermediate to high IL-10 producer genotype than in the recipients with low TNF-alpha combined with low IL-10 producer genotype (62.5% vs 8.5%, P<a0.01). No relations were identified between TGF-beta1, IL-6, IFN-gamma gene polymorphisms and the incidence of acute rejection. CONCLUSION: TNF-alpha and IL-10 gene polymorphism may significantly influence the incidence of acute rejection episodes in sensitized kidney transplants, for whom determination of TNF-alpha and IL-10 genotype might help design feasible immunosuppressive protocols.

Acute Disease↗

[Application of multiplex polymerase chain reaction in rapid identification of Mycobacterium bovis BCG].

OBJECTIVE: To establish a method for the rapid identification of Mycobacterium bovis BCG. METHODS: A genomic region designated RD1 was found to be deleted from BCG strains, but present in other strains of Mycobacterium bovis and other members of the Mycobacterium tuberculosis complex (MTC) including Mycobacterium tuberculosis, Mycobacterium africanum, and Mycobacterium microti. With this information, a multiplex PCR method, developed to detect the deletion of RD1, was used to differentiate BCG strains from other strains of Mycobacterium bovis and other members of MTC. RESULTS: RD1 was shown to be absent in 5 BCG vaccine strains and 2 BCG strains isolated from an infant who died of systemic disseminated infection induced by BCG vaccination, but it was present in 3 Mycobacterium bovis standard strains, 6 Mycobacterium bovis strains isolated from diseased cows, deer or patients with pulmonary tuberculosis and other MTC strains including Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains, 48 Mycobacterium tuberculosis strains isolated from patients with pulmonary tuberculosis, and 3 Mycobacterium africanum standard strains. CONCLUSION: The multiplex PCR method is simple, rapid, and specific for the identification of BCG among strains of MTC, and is applicable in clinical laboratories.

Mycobacterium bovis↗

[Genes mapping on rice allelopathy against barnyardgrass].

By using the relay seeding technique with slight modification, a population of 134 recombinant inbred lines (RILs) derived from a cross between indica rice (Oryza sativa L.) cultivar Zhong 156 x Gumei 2 and contained 168 DNA markers covering all 12 chromosomes with 1447.9 cM spans was employed to evaluate the rice allelopathic effect on barnyardgrass [Echinochloa crus-galli (I.) Beauv.]. The phenotyping values of the biomass of barnyardgrass infested with rice materials were employed to map the genes of allelopathic activity on barnyardgrass. One main effect of QTL on 7 chromosomes was identified, which explained 32.30% of the phenotypic variation. Six pairs of digenic epistatic loci were also detected, which collectively explained 47.83% of the phenotypic variation. The main QTL and epistatic loci totally explained 80.13% of the phenotypic variation of allelopathic activity.

Biomass↗

Involvement of protein tyrosine kinase in Toll-like receptor 4-mediated NF-kappa B activation in human peripheral blood monocytes.

Bacterial lipopolysaccharide (LPS) is a powerful activator of the innate immune system. Exposure to LPS induces an inflammatory reaction in the lung mediated primarily by human blood monocytes and alveolar macrophages, which release an array of inflammatory chemokines and cytokines including IL-8, TNF-alpha, IL-1beta, and IL-6. The signaling mechanisms utilized by LPS to stimulate the release of cytokines and chemokines are still incompletely understood. Pretreatment with the protein tyrosine kinase-specific inhibitors genistein and herbimycin A effectively blocked LPS-induced NF-kappaB activation as well as IL-8 gene expression in human peripheral blood monocytes. However, when genistein was added 2 min after the addition of LPS, no inhibition was observed. Utilizing a coimmunoprecipitation assay, we further showed that LPS-stimulated tyrosine phosphorylation of Toll-like receptor 4 (TLR4) may be involved in downstream signaling events induced by LPS. These findings provide evidence that LPS-induced NF-kappaB activation and IL-8 gene expression use a signaling pathway requiring protein tyrosine kinase and that such regulation may occur through tyrosine phosphorylation of TLR4.

Drosophila Proteins↗

High efficiency genetic modification of hair follicles and growing hair shafts.

A technique for genetic modification of hair follicles was developed which results in efficient alteration of the hair shaft phenotype. High-level in vivo transgene expression was maintained in hair follicles such that growing hair shafts were phenotypically altered. Mouse anagen skin fragments, maintained in histoculture, were genetically modified at high efficiency with adenoviral-GFP. The histocultured skin fragments were treated with collagenase which made hair follicles accessible to the adenoviral GFP gene, allowing high-efficiency transduction. These skin fragments were subsequently grafted on to nude mice where GFP was readily visualized in as many as 75% of hair follicles. Most follicles produced GFP-fluorescent growing hair shafts. This technique has produced efficient genetic modification of the hair shaft.

Adenoviridae↗

Synthesis and thrombolytic activity of pseudopeptides related to fibrinogen fragment.

Two kinds of linkers consisting of 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, ARPAK, GRPAK and QRPAK were synthesized. The thrombolytic activities in vivo indicated that the coupling position of 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in the peptides effected on the potencies significantly. When the C-terminal of the peptides was amidated by 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, the thrombolytic potency of the peptides was enhanced or kept. When the N-terminal of the peptides was acylated by 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, however, the thrombolytic effect of the peptides was banished. The expected specific beta II'-turn conformation and the stability to trypsin in the pseudopeptides with 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in its C-terminal may be responsible for the enhanced thrombolytic potency.

Animals↗

The relationship between (99m)Tc-MIBI uptakes and tumor cell death/proliferation state under irradiation.

To evaluate the potential of 99mTc-MIBI imaging to monitor cellular viability of tumor post-irradiation, Ehrlich carcinoma tissues were exposed to 60Co at different single dose (0, 5, 10, 15 and 20 Gy, respectively) and the following protocol were performed at 6 h pre-irradiation and 24, 72 and 144 h post-irradiation, respectively: (1) 99mTc-MIBI planar scintigraphy was performed. Uptake of 99mTc-MIBI was expressed as differential uptake ratio (DUR) and tumor-to-non-target ratio (T/NT). (2) Apoptosis index (AI), percent of necrosis area (PNA) and Proliferating cell nuclear antigen integral absorbance (PCNA-IA)were measured. DUR and T/NT decreased with radiation dose escalating and post-irradiation time prolonging. At 24 h post-irradiation, DUR or T/NT was inversely correlated with AI or PNA (r=-0.849, -0.829, -0.883, -0.855, respectively, n=33, P<0.01) and positively correlated with PCNA-IA (r=0.789, 0.742, respectively, n=33, P<0.01). At 72 and 144 h post-irradiation, DUR or T/NT was only inversely correlated with PNA (r=-0.967, -0.956, -0.915, -0.886, respectively, n=33, P<0.01). It is suggested that 99mTc-MIBI uptake of tumor cell correlated with the changes of cell viability after irradiation. 99mTc-MIBI imaging may be a potential method to monitor tumor cell viability or therapeutic response after irradiation.

Animals↗

Determination of the docetaxel vehicle, polysorbate 80, in patient samples by liquid chromatography-tandem mass spectrometry.

A new simple method was developed for the quantitative determination of the docetaxel (Taxotere) vehicle, polysorbate 80 (Tween 80), in human plasma. Calibration curves were constructed in the range of 1-100 microg/ml, using paclitaxel (0.01 mM) as internal standard, and were analyzed using a power fit with equal weighting. Sample pretreatment involved a one-step extraction with acetonitrile-n-butyl chloride (1:4, v/v). The analytes were separated on a Waters X-Terra MS column (50x2.1 mm I.D.) packed with 3.5-microm ODS material, and eluted with methanol-water (9:1, v/v) containing 0.1% formic acid. The column effluent was monitored by tandem mass spectrometry with electrospray ionization. The overall extraction efficiency was 50-60%, with values for precision and accuracy of < or =16% and <15% relative error, respectively. Our current method is approximately 60-100-fold more sensitive than previous assays, and will be used to define Tween 80 disposition in patients receiving Taxotere.

Antineoplastic Agents, Phytogenic↗

Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation.

Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.

Animals↗

Vascular smooth muscle cell proliferation requires both p38 and BMK1 MAP kinases.

Vascular smooth muscle cell (VSMC) proliferation is a key event in the progression of atherosclerosis. Induction of both c-fos (through the transcription factor Elk-1) and c-jun, both immediate early genes, is important for the stimulation of VSMC proliferation and migration. It was earlier found that p38 mitogen-activated protein (MAP) kinase upregulates c-jun gene transcription through phosphorylation of two myocyte enhancer factor 2 (MEF2) family transcription factors, MEF2A and MEF2C, while big MAP kinase 1 (BMK1) may upregulate c-jun gene transcription through MEF2A, MEF2C, and also MEF2D. Here, we report that inhibition of BMK1 by a dominant negative form of MEK5 or pharmacologic inhibition of p38 by SB 203580 additively suppress serum-induced VSMC proliferation. This additive effect of p38 and BMK1 inhibition implies that these two kinases coordinately regulate MEF2 transcription factors. The exclusive activation of MEF2D by BMK1 appears required for this cooperative upregulation of c-jun in VSMC, and coactivation of p38 and BMK1 also has additive effects on the activation of a reporter gene linked to the c-jun promoter in our experimental system. Thus, coordinate activity of both the p38 and BMK1 pathways appears necessary for optimal transcription of c-jun and, pari pasu, VSMC proliferation. These results may have implications for the future design of pharmacologic agents for inhibition of VSMC growth.

Animals↗

Alpha-tocopheryl succinate, an agent with in vivo anti-tumour activity, induces apoptosis by causing lysosomal instability.

Certain vitamin E analogues, such as alpha-tocopheryl succinate (alpha-TOS), exhibit in vivo anti-tumour activity and, in vitro, induce apoptosis of cultured tumour cells. In the present study we report that these effects may be explained, at least in part, by destabilization of lysosomal membranes. alpha-TOS, but not alpha-tocopheryl acetate or alpha-tocopherol (alpha-TOH), induced early lysosomal destabilization followed by apoptosis. Similar effects were observed with beta-TOS, whereas beta-TOH was inactive. Cathepsin D-deficient cells were more resistant to alpha-TOS than their normal counterparts, and featured delayed caspase activation. Possible detergent and lysosomotropic effects of alpha- and beta-TOS were suggested by their haemolytic activity in an in vitro test and their release of beta-galactosidase from isolated lysosomes, whereas the non-succinylated analogues were inactive. The pro-apoptotic activity of alpha-TOS was pH-dependent, being greater at lower pH, typical of the interstitium of solid tumours. These findings indicate that lysosomal destabilization may partially or fully explain the induction of apoptosis in cultured cells by alpha-TOS and the mechanism whereby this agent exerts in vivo anti-tumour effects.

Antineoplastic Agents↗

Synthesis and antithrombotic activity of carbolinecarboxyl RGD sequence.

3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, RGDS, RGDV, RGDF and their linkers were synthesized. The anti-aggregation and adhesion of platelet indicated that the in vitro activities of the linkers remained at the same level as RGDS, RGDV, and RGDF (p>0.05). The antithrombotic activities in vivo suggested, however, that the potencies of RGDS, RGDV and RGDF were enhanced by the introduction of 3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxyl group into their alpha amino group (p<0.05, 0.01 or 0.001).

Animals↗

Non-standard insulin design: structure-activity relationships at the periphery of the insulin receptor.

The design of insulin analogues has emphasized stabilization or destabilization of structural elements according to established principles of protein folding. To this end, solvent-exposed side-chains extrinsic to the receptor-binding surface provide convenient sites of modification. An example is provided by an unfavorable helical C-cap (Thr(A8)) whose substitution by favorable amino acids (His(A8) or Arg(A8)) has yielded analogues of improved stability. Remarkably, these analogues also exhibit enhanced activity, suggesting that activity may correlate with stability. Here, we test this hypothesis by substitution of diaminobutyric acid (Dab(A8)), like threonine an amino acid of low helical propensity. The crystal structure of Dab(A8)-insulin is similar to those of native insulin and the related analogue Lys(A8)-insulin. Although no more stable than native insulin, the non-standard analogue is twice as active. Stability and affinity can therefore be uncoupled. To investigate alternative mechanisms by which A8 substitutions enhance activity, multiple substitutions were introduced. Surprisingly, diverse aliphatic, aromatic and polar side-chains enhance receptor binding and biological activity. Because no relationship is observed between activity and helical propensity, we propose that local interactions between the A8 side-chain and an edge of the hormone-receptor interface modulate affinity. Dab(A8)-insulin illustrates the utility of non-standard amino acids in hypothesis-driven protein design.

Amino Acid Sequence↗

Diasteroselective cyclizations with enantiopure malonaldehyde monocycloacetals.

The synthesis of a series of enantiopure malonaldehyde monocycloacetals is described. Treatment of 8b with L-tryptophan methyl ester, 5-methoxytryptamine, and tryptamine, respectively, in the Pictet-Spengler condensation gave the corresponding enantiomerically pure key precursors 1-3 and 17-21 in only two steps. Using a chiral amino-diol successfully realized the kinetic resolution of racemic carbolines 23 and 24.

Journal Article↗