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Biomedical subjects

Yi Miao

Publications and source records attributed to Yi Miao.

18 recordsLinked to original sources

NRAGE suppresses metastasis of melanoma and pancreatic cancer in vitro and in vivo.

We previously reported that human NRAGE could significantly alter the cellular skeleton and inhibit cell-cell adhesion, suggesting that human NRGAE play a potential role in cellular motility. Here, we report overexpression of human NRAGE in PANC-1 and B16-Bl6 cells could significantly suppress the metastasis of these cells in vitro and in vivo. Consistently, PANC-1 with stable silencing of NRAGE by RNA interference, exhibits a more metastatic phenotype than the native cell. Expression of epithelial proteins, including E-cadherin and beta-catenin is down regulated in siRNA-NRAGE PANC-1 cells. Further studies find that overexpression of human NRAGE suppresses the mRNA expression and activity of MMP2 significantly. Summary, our studies indicate for the first time that NRAGE could suppress metastasis of melanoma and pancreatic cancer probably through downregulation of MMP-2.

Animals↗

Synthesis, DNA affinity, and antiprotozoal activity of linear dications: Terphenyl diamidines and analogues.

Diamidines 10a-g and 18a,b were obtained from dinitriles 9a-g and 15a,b by treatment with lithium trimethylsilylamide or upon hydrogenation of bis-O-acetoxyamidoximes. Dinitriles 9a-g were prepared via Suzuki reactions between arylboronic acids and arylnitriles. Potential prodrugs 12a-f and 17 were prepared via methylation of the diamidoximes 11a-f and 16a. Significant DNA affinities for rigid-rod molecules were observed. Compounds 10a, 10b, 10d, 18a, and 18b show IC50 values of 5 nM or less against Trypanosoma brucei rhodesiense (T. b. r.) and 10a, 10b, 10e, 18a, and 18b gave similar ones against Plasmodium falciparum (P.f.). The dications, 10a, 10d, 10f, and 10g are more active than furamidine in vivo. The prodrugs are only moderately effective on oral administration. Mouse liver microsome bioconversion of the methamidoxime prodrugs is significantly reduced from that of pafuramidine and suggests that the in vivo efficacy of these prodrugs is, in part, due to poor bioconversion.

Administration, Oral↗

Dicationic DNA-targeted antiprotozoal agents: naphthalene replacement of benzimidazole.

A series of naphthalene analogues of highly active benzimidazole diamidines were synthesized using sequential Stille and Suzuki coupling reactions for preparation of the bis-nitrile intermediates. All of the diamidines showed strong DNA affinities as judged by high DeltaTm values with poly(dA-dT). The dicationic compounds were quite active in vitro versus Trypanosoma brucei rhodesiense (T. b. r.) exhibiting IC50 values ranging from 4 to 98 nM. These compounds were also active versus Plasmodium falciparum (P. f.) giving IC50 values ranging from 4 to 33 nM. Two of the compounds showed good activity in vivo in the STIB900 model for acute African trypanosomiasis; one gave 3/4 cures and the other gave 4/4 cures on ip dosage of 20 mg/kg for 4 days. The amidoxime prodrugs of the naphthalene analogues were essentially ineffective.

Animals↗

Changes of inducible protein-10 and regulated upon activation, normal T cell expressed and secreted protein in acute rejection of pancreas transplantation in rats.

AIM: To investigate the role of IFN-gamma inducible protein -10 (IP-10) and regulated upon activation, normal T cell expressed and secreted (RANTES) protein in acute pancreatic allograft rejection in rats. METHODS: An experimental pancreas transplantation model was established using diabetic SD rats as the recipient, induced by applying streptozocin (STZ). Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group (group A, n = 24) and allograft group (group B, n = 24) in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry. RESULTS: In group B (allograft group), the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A (isograft group). CONCLUSION: Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.

Animals↗

CD44v6 in peripheral blood and bone marrow of patients with gastric cancer as micro-metastasis.

AIM: To detect the expression of CD44 correlated with the ability of micro-metastasis in peripheral blood and bone marrow of patients with gastric cancer and to deduce its clinical significance. METHODS: Preoperative peripheral blood and bone marrow specimens from 46 patients with gastric cancer and 6 controls were studied by semi-quantitative RT-PCR amplification of CD44v6mRNA. Preoperative and postoperative peripheral blood specimens from 40 patients with gastric cancer and 14 controls were studied by quantitative RT-PCR amplification of CD44v6mRNA in the corresponding period. RESULTS: Semi-quantitative RT-PCR amplification showed that CD44v6mRNA expression of peripheral blood and bone marrow was positive in 39 (84.8%) and 40 (86.9%) of 46 patients with gastric cancer, respectively. In peripheral blood, CD44v6mRNA expression was positive for diffuse type in 30 (93.8%) of 32 patients and for intestinal type in 9 (64.3%) of 14 patients. On the other hand, in bone marrow, CD44v6mRNA expression was positive for diffuse type in 31 (96.9%) of 32 patients and for intestinal type in 10 (71.4%) of 14 patients. There was a significant difference between the diffuse type and intestinal type. Quantitative RT-PCR amplification demonstrated that CD44v6mRNA was not expressed in the peripheral blood of controls and CD44v6mRNA expression was positive for preoperative peripheral blood in 40 patients with gastric cancer, the expression levels being from 4.9 x 10(8) - 3.2 x 10(11) copies/g RNA. The average expression level of CD44v6mRNA in peripheral blood was 3.9 x 10(10) copies/g RNA. The expression levels of CD44v6mRNA in peripheral blood in gastric cancer patients after curative operation increased from 5.5 x 10(6) to 7.6 x 10(9) copies/g RNA and the average level was 2.4 x 10(8) copies/g RNA (Figure 3B) (P = 0.00496). After curative operation, the expression level decreased markedly. CONCLUSION: Semi-quantitative and quantitative RT-PCR amplification for CD44v6mRNA is a sensitive and specific method for the detection of micro-metastasis in peripheral blood and bone marrow, which might be used as an indicator of tumor burden and therapeutic effect.

Adult↗

Electrodes and multiple electrode systems for radio frequency ablation: a proposal for updated terminology.

OBJECTIVE: Research on technology for soft tissue radio frequency (RF) ablation is ever advancing. A recent proposal to standardize terminology of RF electrodes only deals with the most frequently used commercial electrodes. The aim of this study was to develop a logical, versatile, and unequivocal terminology to describe present and future RF electrodes and multiple electrode systems. MATERIALS AND METHODS: We have carried out a PubMed search for the period from January 1st 1990 to July 1st 2004 in seven languages and contacted the six major companies that produce commercial RF electrodes for use in the liver. In a first step, names have been defined for the five existing basic designs of single-shaft electrode. These names had to be unequivocal, descriptive of the electrode's main working principle and as short as possible. In a second step, these basic names have been used as building blocks to describe the single-shaft electrodes in combination designs. In a third step, using the same principles, a logical terminology has been developed for multiple electrode systems, defined as the combined use of more than one single-shaft RF electrode. RESULTS: Five basic electrode designs were identified and defined: plain, cooled, expandable, wet, and bipolar electrodes. Combination designs included cooled-wet, expandable-wet, bipolar-wet, bipolar-cooled, bipolar-expandable, and bipolar-cooled-wet electrodes. Multiple electrode systems could be characterized by describing several features: the number of electrodes that were used (dual, triple, etc.), the electric mode (monopolar or bipolar), the activation mode (consecutive, simultaneous or switching), the site of the inserted electrodes (monofocal or multifocal), and the type of single-shaft electrodes that were used. CONCLUSION: In this terminology, the naming ofthe basic electrode designs has been based on objective criteria. The short and unequivocal names of the basic designs can easily be combined to describe current and future combination electrodes. This terminology provides an exact and complete description of the versatile novel multiple electrode systems.

Catheter Ablation↗

Engineering mouse apolipoprotein A-I into a monomeric, active protein useful for structural determination.

Apolipoprotein AI (apoAI), the major protein component of HDL, is one of the best predictors of coronary artery disease (CAD), with high apoAI and HDL levels being correlated with low occurrences of CAD. The primary function of apoAI is to recruit phospholipid and cholesterol for assembly of HDL particles. Like other exchangeable apolipoproteins, lipid-free apoAI forms a mixture of different oligomers even at 1.0 mg/mL. This self-association property of the exchangeable apolipoproteins is closely associated with the lipoprotein-binding activity of this protein family. It is unclear if the self-association property of apolipoprotein is required for its lipoprotein-binding activity. We developed a novel method for engineering an oligomeric protein to a monomeric, biologically active protein. Using this method, we generated a monomeric mouse apoAI mutant that is active. This mutant contains the first 216 residues of mouse apoAI and replaces six hydrophobic residues with either polar or smaller hydrophobic residues at the defined positions (V118A/A119S/L121Q/T191S/T195S/T199S). Cross-linking results show that this mutant is greater than 90% monomeric at 8 mg/mL. CD, DSC, and NMR results indicate that the mutant maintains an identical secondary, tertiary structure and stability as those of the wild-type mouse apoAI. Lipid-binding assays suggest that the mutant shares an equal lipoprotein-binding activity as that of the wild-type apoAI. In addition, both the monomeric mutant and the wild-type protein make nearly identical rHDL particles. With this monomeric mouse apoAI, high-quality NMR data has been collected, allowing for the NMR structural determination of lipid-free apoAI. On the basis of these results, we conclude that this apoAI mutant is a monomeric, active apoAI useful for structural determination.

Animals↗

Out-of-shape DNA minor groove binders: induced fit interactions of heterocyclic dications with the DNA minor groove.

DB921 and DB911 are benzimidazole-biphenyl isomers with terminal charged amidines. DB911 has a central meta-substituted phenyl that gives it a shape similar to those of known minor groove binding compounds. DB921 has a central para-substituted phenyl with a linear conformation that lacks the appropriate radius of curvature to match the groove shape. It is thus expected that DB911, but not DB921, should be an effective minor groove binder, but we find that DB921 not only binds in the groove but also has an unusually high binding constant in SPR experiments (2.9 x 10(8) M(-)(1), vs 2.1 x 10(7) M(-)(1) for DB911). ITC thermodynamic analysis with an AATT sequence shows that the stronger binding of DB921 is due to a more favorable binding enthalpy relative to that of DB911. CD results support minor groove binding for both compounds but do not provide an explanation for the binding of DB921. X-ray crystallographic analysis of DB921 bound to AATT shows that an induced fit structural change in DB921 reduces the twist of the biphenyl to complement the groove, and places the functional groups in position to interact with bases at the floor of the groove. The phenylamidine of DB921 forms indirect contacts with the bases through a bound water. The DB921-water pair forms a curved binding module that matches the shape of the minor groove and provides a number of strong interactions that are not possible with DB911. This result suggests that traditional views of compound curvature required for minor groove complex formation should be reevaluated.

Amidines↗

Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted antiprotozoal agents.

A series of near-linear biphenyl benzimidazole diamidines 5a-h were synthesized from their respective diamidoximes (4a-h), through the bis-O-acetoxyamidoxime, followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd-C. Compounds 4a-h were obtained in three steps, starting with the Suzuki coupling reaction of the appropriate haloarylcarbonitriles 1a-g or 4-bromo-2-fluorobenzaldehyde with 4-formylphenylboronic acid or 4-cyanophenylboronic acid to form the anticipated 4-formylbiphenyl carbonitrile analogues 2a-h. Subsequent condensation of the formyl derivatives 2a-h with 3,4-diaminobenzonitrile in the presence of sodium bisulfite or 1,4-benzoquinone gave the desired dinitriles 3a-h, the precursors for 4a-h. All the diamidines showed strong DNA affinities, as judged by high Delta Tm values with poly(dA.dT)2) The compounds were quite active in vitro versus Trypanosoma brucei rhodesiense, giving IC50 values ranging from 3 to 37 nM. These compounds were even more active versus Plasmodium falciparum, exhibiting IC50 values ranging from 0.5 to 23 nM. The compounds showed moderate to good activity in vivo in the STIB900 model for acute African trypanosomiasis. The most active compounds 5b and e gave 3/4 cures on an IP dosage of 20 mg/kg.

Animals↗

Electrodes and multiple electrode systems for radiofrequency ablation: a proposal for updated terminology.

Research on technology for soft tissue radiofrequency (RF) ablation is ever advancing. A recent proposal to standardise terminology of RF electrodes only deals with the most frequently used commercial electrodes. The aim of this study was to develop a logical, versatile and unequivocal terminology to describe present and future RF electrodes and multiple electrode systems. We have carried out a PubMed search for the period from January 1 1990 to July 1 2004 in seven languages and contacted the six major companies that produce commercial RF electrodes for use in clinic. In a first step, names have been defined for the five existing basic designs of single-shaft electrode. These names had to be unequivocal, descriptive of the electrode's main working principle and as short as possible. In a second step, these basic names have been used as building blocks to describe the single-shaft electrodes in combination designs. In a third step, using the same principles, a logical terminology has been developed for multiple electrode systems, defined as the combined use of more than one single-shaft RF electrode. Five basic electrode designs were identified and defined: plain, cooled, expandable, wet and bipolar electrodes. Combination designs included cooled-wet, expandable-wet, bipolar-wet, bipolar-cooled, bipolar-expandable and bipolar-cooled-wet electrodes. Multiple electrode systems could be characterised by describing several features: the number of electrodes that were used (dual, triple, ...), the electric mode (monopolar or bipolar), the activation mode (consecutive, simultaneous or switching), the site of the inserted electrodes (monofocal or multifocal), and the type of single shaft electrodes that were used. In this terminology, the naming of the basic electrode designs has been based on objective criteria. The short and unequivocal names of the basic designs can easily be combined to describe current and future combination electrodes. This terminology provides an exact and complete description of the versatile novel multiple electrode systems.

Catheter Ablation↗

Binding sites of [Ru(bpy)2(H2O)2](BF4)2 with sulfur- and histidine-containing peptides studied by electrospray ionization mass spectrometry and tandem mass spectrometry.

The composition and binding sites of cis-[Ru(II)(bpy)2]2+-bound sulfur-containing peptides of Met-Arg-Phe-Ala, glutathione and oxidized glutathione, and also histidine-containing peptide of oxidized insulin B chain, were investigated by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). The composition of Ru(II)-containing peptides was precisely determined by ESI-MS, zoom scan and simulation of isotope distribution patterns. MS/MS analysis shows that, in sulfur-containing peptides, the Ru(II) complex prefers to anchor to a carboxyl group, although some other potential binding sites of thiol, thioether and N-terminal amino groups present in these peptides, and in oxidized insulin B chain, Ru(II) first anchors to His10, then either to the hydroxyl group of Thr27 or to the carboxyl group of Ala30. Its secondary structure and microenvironment surrounding the potential binding sites may affect the binding ability of cis-[Ru(II)(bpy)2]2+ to oxidized insulin B chain.

2,2'-Dipyridyl↗

Interactions of platinum(II) complexes with sulfur-containing peptides studied by electrospray ionization mass spectrometry and tandem mass spectrometry.

Reactions of two platinum(II) complexes, cis-[Pt(NH3)2(H2O)2]2+ (Pt1) and cis-[Pt(en)(H2O)2]2+ (Pt2), with several sulfur-containing peptides, have been investigated by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). The species produced in the reactions were detected with ESI-MS, and MS/MS analysis was performed to probe structural information. Collision-induced dissociation revealed different dissociation pathways for the main reaction products of the two platinum(II) complexes with the same peptides. The major difference is the prominent loss of ammonia ligand for complexes of Pt1 due to the strong trans effect of sulfur, whereas the loss of ethylenediamine (en) ligand from Pt2 complexes is less favored, reflecting the chelating effect of the bidentate ligand. Despite the differences in dissociation patterns, Pt1 and Pt2, in general, form structurally similar complexes with the same peptides. In the reactions with Met-Arg-Phe-Ala they both produce a N,S-chelate ring through the N-terminal NH2 and sulfur of the Met residue, and in the reactions with Ac-Met-Ala-Ser they bind to the sulfur of Met and deprotonate an amide nitrogen upstream from the anchor site. Both of them are able to promote hydrolysis of the peptides. In reactions with glutathione they both form four-membered Pt2S2 rings and Pt-S-Pt bonding through the bridging thiolate ligand, although the reaction rate is much slower for Pt2 due to steric hindrance of the en ligand.

Organoplatinum Compounds↗

[Combined multiple organ resection in 16 patients with adenocarcinoma of the body or tail of the pancreas].

OBJECTIVE: To investigate the feasibility and therapeutic results of multiple organ resection in patients with tumor of the body and tail of pancreas. METHODS: The clinical and pathological data were analysed in 16 consecutive patients with neoplasm of the body and tail of pancreas from 1999 to 2004 retrospectively. RESULTS: Multiple organ resection was performed in 6 cases of primary pancreatic adenocarcinoma of the body and tail (3 cases of pancreatic cancer, 2 cases of malignant glucagonoma, and 1 case of well-differentiated pancreatic stromal sarcoma) and 10 cases of extrapancreatic malignancy (4 cases of gastric cancer, 2 cases of gastric leiomyosarcoma, 1 case of duodenal cancer, and 3 cases of colon cancer of hepatic flexure). Distal pancreatectomy with splenectomy was performed in all cases. In addition, 10 patients received splenic flexure colectomy, 6 patients received distal gastrectomy, 3 patients received left nephrectomy, left colectomy, total gastrectomy, liver lobe resection, left adrenalectomy, and local diaphragma resection, and 2 patients received transverse colectomy, subtotal colectomy, proximal proctectomy, proximal gastrectomy, and duodenectomy. No perioperative death and severe complications were observed. Patients with primary pancreatic cancer or pancreatic stromal sarcoma died within 1 year. Two patients with malignant glucagonoma died 51 and 39 months later. The 3-year survival rate was 70% in 10 patients with extrapancreatic malignancy, among which 2 patients with enteric cancer have survived 37 and 48 months. CONCLUSION: Radical combined multiple organ resection may be performed actively in appropriately selected patients.

Adenocarcinoma↗

Value of t2-weighted magnetic resonance imaging early after myocardial infarction in dogs: comparison with bis-gadolinium-mesoporphyrin enhanced T1-weighted magnetic resonance imaging and functional data from cine magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Magnetic Resonance Imaging (MRI) has proved to provide noninvasive methods to investigate the functional repercussion of myocardial infarction and to measure infarct size with specific contrast agents. In this study, we evaluate whether the combination of T2-weighted and contrast-enhanced T1-weighted MRI could detect and discern necrotic and ischemic, but salvageable, myocardium. METHODS: Reperfused myocardial infarction was surgically induced in 14 dogs. T1- and T2-weighted MRI was performed 6 hours after administration of the necrosis avid contrast agent Gadophrin-2 at 0.05 mmol/kg. Gradient-echo cine MRI series were performed at baseline and at 6 hours. Quantification of myocardial infarction was performed with triphenyltetrazolium chloride staining. RESULTS: There was a strong correlation between of postcontrast T1-weighted MRI and histomorphometry (r2 = 0.98, P < 0.01). T2-weighted MRI overestimated the infarct size by 10.5% +/- 4.3% of left ventricular area. A good correlation was found between hyperintense areas on T2-weighted images and the percentage of dysfunctional areas on cine MRI (r2 = 0.84, P < 0.01). In regions with increased signal intensity on T2-weighted MRI, a decreased maximal systolic thickening (11.8% +/- 4.9%, P = 0.043) was found. CONCLUSION: In this study, the difference between the hyperintense areas on T2-weighted and enhanced T1-weighted images after myocardial infarction likely represents viable myocardium.

Animals↗

Early rejection and pathological changes in combined pancreaticoduodenal and kidney allotransplantation in pigs.

OBJECTIVE: To study the markers of early rejection and pathological changes in simultaneous pancreaticoduodenal and kidney transplantation (SPKT). METHODS: Thirty hybrid pigs were used as donors and recipients. A renoportal end-to-end anastomosis between the left renal vein and the distal end of the portal vein was performed. Two vascular end-to-side anastomoses between the donor portal vein and recipient inferior vena cava, and between the donor aortic segment including the celiac and superior mesenteric, and left renal arteries and recipient abdominal aorta were carried out. Pancreas exocrine secretion drainage was established with duodenocystostomy. Ureterostomosis of the graft was performed. Urine amylase level, fasting blood glucose and urine volumes of kidney allograft were monitored, and pathological changes of graft were observed. RESULTS: Of 15 recipients, 2 died of disturbance of internal environment and anastomotic bleeding, respectively. Satisfactory results were obtained in the remaining 13 recipients. The changes of urine amylase concentration were prior to those of fasting blood glucose and urine volumes of kidney allograft. The degree of rejection of the kidney allograft was more severe than that of the pancreas and duodenum allograft. CONCLUSIONS: Urine amylase is the early marker of acute rejection in SPKT with bladder drainage of pancreatic exocrine secretion. The pathological change of kidney allograft is most significant in SPKT.

Amylases↗