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Biomedical subjects

Ming Zhao

Publications and source records attributed to Ming Zhao.

At least 109 records · Page 6Linked to original sources
PubMed2004

Synthesis and thrombolytic activity of carboline-3-carboxylic acid modified metabolites of Ala-Arg-Pro-Ala-Lys.

From the metabolism of H-Ala-Arg-Pro-Ala-Lys-OH, four metabolites, H-Pro-Ala-Lys-OH, H-Arg-Pro-Ala-Lys-OH, H-Ala-Arg-Pro-OH, and H-Ala-Arg-Pro-Ala-OH were identified. In order to find a new lead compound of thrombolytic peptide, 3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid was introduced to the N- and C-terminal of the metabolites by use of the common coupling strategy. Under this condition, the pseudopeptides (5a-d and 7a-d) were obtained with a good yield. The thrombolytic activities of 3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid containing oligopeptides were evaluated in vitro and in vivo. The result indicated that the thrombolytic activity of the pseudopeptide depended on the sequence and the modification pattern of the metabolites, and only when 3S-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid was introduced into the C-terminal of H-Pro-Ala-Lys-OH or H-Arg-Pro-Ala-Lys-OH, the desirable thrombolytic activity was retained and enhanced significantly.

Animals↗
PubMed2004

Suppression of bcl-2 gene by RNA interference increases chemosensitivity to cisplatin in nasopharyngeal carcinoma cell line CNE1.

To explore the effect of suppressing BCL-2 expression using RNA interference (RNAi) technique in nasopharyngeal carcinoma cell line CNE1. CNE1 cell lines stably expressing shRNAs targeted bcl-2 and GL3 gene were established and gene expression inhibition was assessed by Western blotting analysis. The effect of suppressing bcl-2 by RNAi on cell growth was studied, the apoptosis induction and the sensitization of CNE1 cells to cisplatin were quantified by MTT assays and flow cytometry. The results showed that: stable transfection of CNE1 cells with vectors expressing shRNAs against bcl-2 decreased the expression of BCL-2 protein; suppression of BCL-2 expression did not affect cell proliferation but could increase the chemosensitivity to cisplatin in CNE1 cells. This will help physicians to make some clinical trials of gene therapy on nasopharyngeal carcinoma by RNAi.

Antineoplastic Agents↗
PubMed2004

Limited cerebrospinal fluid penetration of docetaxel.

Our purpose was to investigate the cerebrospinal fluid (CSF) penetration of docetaxel in cancer patients. Docetaxel was administered as a 1-h infusion at a dose of 75 mg/m2 to two patients with metastatic breast cancer and leptomeningeal carcinomatosis. CSF samples were obtained using a lumbar puncture up to a 72-h time period. Total and unbound docetaxel concentrations in plasma and CSF were determined by liquid chromatography (lower limit of quantitation: 0.5 nM for plasma and 0.050 nM for CSF) and equilibrium dialysis, respectively. The pharmacokinetics of docetaxel in plasma are in line with data of previous studies. The concentrations of docetaxel in CSF did not follow the general pattern in plasma, with relatively stable concentrations over the 72-h time period. The fraction of unbound docetaxel in plasma ranged from 6 to 13%, while that in CSF ranged from 67 to 103%. For total and unbound docetaxel, the CSF to plasma concentration ratio progressively increased in 72 h from 0.01 to 0.6% and from 0.1 to 9%, respectively. These data suggest that measurement of unbound docetaxel is required to accurately assess the extent of drug penetration into CSF and that the drug can produce distribution to CSF at levels associated with significant antitumor activity in experimental models.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Operative revision of non-functioning filtering blebs with 5-fluorouracil to regain intraocular pressure control.

PURPOSE: To determine the efficacy of extensive microsurgical needling revision of failed filtering blebs followed by serial 5-fluorouracil subconjunctival injections. METHODS: Thirty-six eyes of 34 consecutive patients with progressive open-angle glaucoma refractory to topical therapy submitted to needling revision as a major procedure. All patients required multiple antiglaucoma medications preoperatively, and had completely flat or densely encapsulated filtering blebs. All patients underwent elaborate needling revision (limbus to superior rectus >8 mm diameter, >3 mm elevation, entry-site sutured with 8-0 vicryl and bleb reformed via paracentesis with viscoelastic) in the operating room, followed by serial 5-fluorouracil. The patients were followed for up to 6 months postoperatively. The main outcome measures were intraocular pressure (IOP) and the number of antiglaucoma medications used. RESULTS: Thirty-one eyes (86%) maintained mean IOP below 15 mmHg postneedling without medication. Overall the mean IOP postneedling was >9 mmHg lower than medicated preoperative levels (P < 0.0001). IOP reduction in encapsulated blebs was marginally superior to that in flat blebs. CONCLUSIONS: Extensive needling revision in the operating room is safe, straightforward, and produces reproducible restoration of filtering function.

Adult↗
PubMed2004

Gene therapy approaches for bone regeneration.

Gene therapy represents a promising approach for delivering regenerative molecules to specific tissues including bone. Several laboratories have shown that virus-based BMP expression vectors can stimulate osteoblast differentiation and bone formation in vivo. Both in vivo and ex vivo transduction of cells can induce bone formation at ectopic and orthotopic sites. Adenovirus and direct DNA delivery of genes encoding regenerative molecules can heal critical-sized defects of cranial and long bones. Although osteogenic activity can be demonstrated for individual BMP vectors, substantial synergies may be achieved using combinatorial gene therapy to express complimentary osteogenic signals including specific combinations of BMPs or BMPs and transcription factors. Further control of the bone regeneration process may also be achieved through the use of inducible promoters that can be used to control the timing and magnitude of expression for a particular gene. Using these types of approaches, it should be possible to mimic natural processes of bone development and fracture repair and, in so doing, be able to precisely control both the amount and type of bone regenerated.

Adenoviridae↗
PubMed2004

Cementoblast delivery for periodontal tissue engineering.

BACKGROUND: Predictable periodontal regeneration following periodontal disease is a major goal of therapy. The objective of this proof of concept investigation was to evaluate the ability of cementoblasts and dental follicle cells to promote periodontal regeneration in a rodent periodontal fenestration model. METHODS: The buccal aspect of the distal root of the first mandibular molar was denuded of its periodontal ligament (PDL), cementum, and superficial dentin through a bony window created bilaterally in 12 athymic rats. Treated defects were divided into three groups: 1) carrier alone (PLGA polymer sponges), 2) carrier + follicle cells, and 3) carrier + cementoblasts. Cultured murine primary follicle cells and immortalized cementoblasts were delivered to the defects via biodegradable PLGA polymer sponges, and mandibulae were retrieved 3 weeks and 6 weeks post-surgery for histological evaluation. In situ hybridization, for gene expression of bone sialoprotein (BSP) and osteocalcin (OCN), and histomorphometric analysis were further done on 3-week specimens. RESULTS: Three weeks after surgery, histology of defects treated with carrier alone indicated PLGA particles, fibrous tissue, and newly formed bone scattered within the defect area. Defects treated with carrier + follicle cells had a similar appearance, but with less formation of bone. In contrast, in defects treated with carrier + cementoblasts, mineralized tissues were noted at the healing site with extension toward the root surface, PDL region, and laterally beyond the buccal plate envelope of bone. No PDL-bone fibrous attachment was observed in any of the groups at this point. In situ hybridization showed that the mineralized tissue formed by cementoblasts gave strong signals for both BSP and OCN genes, confirming its nature as cementum or bone. The changes noted at 3 weeks were also observed at 6 weeks. Cementoblast-treated and carrier alone-treated defects exhibited complete bone bridging and PDL formation, whereas follicle cell-treated defects showed minimal evidence of osteogenesis. No new cementum was formed along the root surface in the above two groups. Cementoblast-treated defects were filled with trabeculated mineralized tissue similar to, but more mature, than that seen at 3 weeks. Furthermore, the PDL region was maintained with well-organized collagen fibers connecting the adjacent bone to a thin layer of cementum-like tissue observed on the root surface. Neoplastic changes were observed at the superficial portions of the implants in two of the 6-week cementoblast-treated specimens, possibly due in part to the SV40-transformed nature of the implanted cell line. CONCLUSIONS: This pilot study demonstrates that cementoblasts have a marked ability to induce mineralization in periodontal wounds when delivered via polymer sponges, while implanted dental follicle cells seem to inhibit periodontal healing. These results confirm the selective behaviors of different cell types in vivo and support the role of cementoblasts as a tool to better understand periodontal regeneration and cementogen-

Absorbable Implants↗
PubMed2004

Effect of sustained gene delivery of platelet-derived growth factor or its antagonist (PDGF-1308) on tissue-engineered cementum.

BACKGROUND: Cementum, a mineralized tissue lining the tooth root surface, is destroyed during the inflammatory process of periodontitis. Restoration of functional cementum is considered a criterion for successful regeneration of periodontal tissues, including formation of periodontal ligament, cementum, and alveolar bone. Short-term administration of platelet-derived growth factor (PDGF) has been shown to partially regenerate periodontal structures. Nonetheless, the role of PDGF in cementogenesis is not well understood. The aim of the present study was to determine the effect of sustained PDGF gene transfer on cementum formation in an ex vivo ectopic biomineralization model. METHODS: Osteocalcin (OC) promoter-driven SV40 transgenic mice were used to obtain immortalized cementoblasts (OCCM). The OCCM cells were transduced with adenoviruses (Ad) encoding either PDGF-A, an antagonist of PDGF signaling (PDGF-1308), a control virus (green fluorescent protein, GFP), or no treatment (NT). The transduced cells were incorporated into polymer scaffolds and implanted subcutaneously into severe combined immunodeficient (SCID) mice. The implants were harvested at 3 and 6 weeks for histomorphometric analysis of the newly formed mineralized tissues. Northern blot analysis was performed to determine the expression levels of mineral-associated genes including bone sialoprotein (BSP), OC, and osteopontin (OPN) in the cell-implant specimens at 3 and 6 weeks. RESULTS: The results indicated mineralization was significantly reduced in both the Ad/PDGF-A and Ad/PDGF-1308 treated specimens when compared to the NT or Ad/GFP groups at 3 and 6 weeks (P<0.01). In addition, the size of the implants treated with Ad/PDGF-A and Ad/PDGF-1308 was significantly reduced compared to implants from Ad/GFP and NT groups at 3 weeks (P<0.05). At 6 weeks, the size of implants and mineral formation increased in NT, Ad/GFP, and Ad/PDGF-A groups, while the Ad/PDGF-1308 treated implants continued to decrease in size and mineral formation (P<0.01). Northern blot analysis revealed that in the Ad/PDGF-A treated implants OPN was increased, whereas OC gene expression was downregulated at 3 weeks. In the Ad/PDGF-1308 treated implants, BSP, OC, and OPN were all downregulated at 3 weeks. At 3 weeks, the Ad/PDGF-A treated implants contained significantly higher multinucleated giant cell (MNGC) density compared to NT, Ad/GFP, and Ad/PDGF-1308 specimens. The MNGC density in NT, Ad/GFP, and Ad/PDGF-A treated groups reduced over time, while the Ad/PDGF-1308 transduced implants continued to exhibit significantly higher MNGC density compared with the other treatment groups at 6 weeks. CONCLUSIONS: The results showed that continuous exposure to PDGF-A had an inhibitory effect on cementogenesis, possibly via the upregulation of OPN and subsequent enhancement of MNGCs at 3 weeks. On the other hand, Ad/PDGF-1308 inhibited mineralization of tissue-engineered cementum possibly due to the observed downregulation of BSP and OC and a persistence of stimulation of MNGCs. These findings suggest that continuous exogenous delivery of PDGF-A may delay mineral formation induced by cementoblasts, while PDGF is clearly required for mineral neogenesis.

Animals↗
PubMed2004

Risk factors for graft survival in sensitized recipients of kidney transplantation.

OBJECTIVE: To investigate the independent prognostic factors for graft survival in sensitized recipients undergoing kidney transplantation, so as to identify the individuals at high risk of graft loss before transplantation. METHODS: A retrospective investigation was conducted in 102 sensitized kidney transplant recipients and 31 relative variables were analyzed with SPSS10.0 software. Using log-rank method, the influence of these variables on short- and long-term graft survivals was evaluated, and Kaplan-Meier analysis was performed to estimate the 1-, 3- and 5-year graft survival rates and half-life. Proportional hazards regression analysis (Cox model) was used to assess the relative risks of the potential variables. RESULTS: In the recipients with a mean half-life of 8.9 years, the 1-, 3- and 5-year graft survival rates were 90%, 85%, and 75%, respectively. By log-rank analysis, the factors affecting short- and long-term graft survivals were identified, namely the recipient age, times of transplantation, levels of panel reactive antibody and the post-operative anti-HLA-IgG antibody, HLA mismatch, renal function, time needing for graft function recovery, presence of acute rejection, delay of graft function recovery and infection, which affected the graft survival demonstrated by Cox model multivariate analysis. CONCLUSION: High-quality donor kidney and minimization of the risk factors for graft survival may insure successful kidney transplantation in sensitized recipients.

Adult↗
PubMed2004

[Testing and analyzing the lung functions in the normal population in Hebei province].

OBJECTIVE: To investigate the lung function of the normal subjects living in Hebei province and its correlative factors such as living circumstance, age, height, and body weight. METHODS: The lung volumes and breath capacities of 1,587 normal subjects were tested by portable spirometers (Scope Rotry) from August to October in 2002. The influences of living circumstance, age, gender, height, and body weight on lung functions were observed and analyzed. RESULTS: No significant difference was found between urban and rural areas in all indexes (P > 0.05); however, significant difference existed between male and female subjects (P = 0.000). The change trends of lung function in male and female subjects were similar. Growth spurt appeared at the age of 12-16 years in male subjects and 12-14 years in female subjects. Vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) reached their peaks at the age of 26-34 years and then decreased with age. Peak expiratory flow (PEF), 25% forced expiratory flow (FEF50%), and 75% forced expiratory flow (FEF75%) appeared at the age of 18 and then went down with age. Both height and weight had a correlation with all the indexes of lung functions, although the influence of height is stronger than weight. CONCLUSIONS: All the indexes of lung function have correlations with age, height, and weight. Lung function changes with aging, therefore different expected values shall be available for the adolescence, young adults, and middle-aged and old people. This study provides reference values of lung function for normal population.

Adolescent↗
PubMed2004

[Risk factors of acute rejection in sensitized kidney transplant recipients].

OBJECTIVE: To identify the risk factors of acute rejection in sensitized recipients undergoing kidney transplantation. METHODS: The clinical data of 102 sensitized kidney transplant recipients were retrospectively analyzed to evaluate the incidence of acute rejection in relation to panel reactive antibodies (PRA), amino acid residual match, postoperative elevation of PRA level and cytokine genotypes. RESULTS: During the follow-up, acute rejection occurred in totally 33 patients, and the incidence was higher in the recipients with high tumor necrosis factor (TNF)-alpha or high interleukin (IL)-10 producer genotype than in those with low TNF-alpha or low/intermediate IL-10 producer genotype (53.1%, 55.0% vs 22.8%, 20.9%, P(18)0.01 respectively). Acute rejection was even more frequent in the recipients with both high TNF-alpha and high/intermediate IL-10 producer genotypes than in those with low TNF-alpha and IL-10 producer genotype (66.7% vs 10.2%, P<0.01). No relations were found between TGF-beta1, IL-6, IFN-gamma gene polymorphisms and the incidence of acute rejection. The incidence in the recipients with PRA level of more than 40% was also higher than those with lower PRA level (<20%, 53.3% vs 22.7%, P<0.05), and the amino acid residual mismatch with 3-4 MM was responsible for a higher incidence in comparison with a mismatch with 0-1 MM (75.0% vs 24.1%, P<0.01). Postoperative elevation of PRA level also increased the risk of acute rejection (45.4% vs 22.4%, P<0.01). CONCLUSION: TNF-alpha, IL-10 gene polymorphism, PRA, amino acid residual mismatch, and increased postoperative PRA level may significantly influence acute rejection in sensitized kidney transplantation recipient, and preoperative evaluation of these factors may benefit the designing of immunosuppressive protocols for these patients.

Adult↗
PubMed2004

[Clinical value of brachytherapy of malignant biliary obstruction after implanting expandable metallic biliary endoprothesis (EMBE)].

BACKGROUND & OBJECTIVE: For malignant biliary obstruction,drainage is the only procedure to cope with jaundice itself. It does not work for neoplasm. Patient will die of disease progress in a short time.With after-loading radiotherapy,radiofrequency ablation(RFA) and port catheter system(PCS) chemotherapy,we can directly apply these methods to treat neoplasm. This study is to investigate the value of after-loading treatment through biliary drainage and local chemotherapy embolism of PCS and RFA on treatment of malignant biliary obstruction after Expandable Metallic stent placement. Materials and Methods 49 cases with malignant biliary obstruction can not or do not be suit for surgical treatment, including hepatic portal tumor 25 cases (17 with primary hepatocellular carcinoma,8 with metastasis carcinoma), biliary carcinoma 11 cases, pancreatic carcinoma 6 cases, Clastkin tumor 7 cases. These patients were divided into four groups in random sampling. One underwent EMBE, the second underwent both EMBE and after-loading treatment,the third group underwent both EMBE and RFA, The last underwent both EMBE and PCS. EMBE of Percutaneous biliary drainage were placed in these patients first. The second group was given after-loading treatment then. The third group was given RFA after EMBE. PCS were done in the last group. Chemotherapeutic agents were infused through PCS according to characteristics of biology and pharmacokinetics. RESULTS: 49 cases were successfully placed EMBE. In 49, 13 cases underwent EMBE, 16 cases underwent after-loading treatment after EMBE, 9 cases received RFA treatment, 11 cases underwent PCS after EMBE. Follow-up time was 1-12 months. For group EMBE: 6 cases (46.1%) developed re-obstruction in 1-3 months, 8 cases(61.5%)died in 2-6 months ,11 cases (84.6%)died in 12 months; for group after-loading:4 cases (25.0%) reobstructed in 1-3 months, 5 cases(31.25%) died in 2-6 months, 6 cases(37.5%) died in 12 months; for group EMBE and RFA: 2 cases (22.2%) reobstructed in 1-3 months ,2 cases (22.2%) died in 2-6 months, 3 cases (33.3%) died in 12 months;for group EMBE and PCS:3 cases (27.27%) reobstructed in 1-3 months ,5 cases (45.45% ) died in 2-6 months, 6 cases (54.54%) died in 12 months. The four groups have significant difference in reobstruction rate and mortality rate, by T-test (P< 0.01). conclusion EMBE combined with brachytherapy is more effective methods than EMBE in treatment of malignant biliary obstruction.

Adult↗
PubMed2003

Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo.

Bone morphogenetic proteins (BMPs) are required for normal postnatal bone formation and osteoblast differentiation. There is evidence from recent studies that BMP signaling in osteoblasts is controlled by an ubiquitin-proteasome regulatory mechanism involving a cascade of enzymatic reactions. The specificity of protein ubiquitination is determined by E3 ubiquitin ligases, which play a crucial role in defining substrate specificity and subsequent protein degradation by 26S proteasomes. We have examined the role of the E3 ubiquitin ligase Smad ubiquitin regulatory factor 1 (Smurf1), a member of the Hect domain family of E3 ubiquitin ligases in osteoblast function. Smurf1 has been found to interact with BMP-activated Smad1 and -5 and to mediate degradation of these Smad proteins. Recently we have found that Smurf1 mediates the protein degradation of the osteoblast-specific transcription factor Runx2/Cbfa1. To determine the role of Smurf1 in osteoblast differentiation, in the present studies we transfected a Smurf1 expression plasmid into 2T3 osteoblast precursor cells and found that Smurf1 overexpression inhibits BMP signaling and osteoblast differentiation. To further investigate the role of Smurf1 in bone formation in vivo, we generated transgenic mice in which expression of the epitope-tagged Smurf1 transgene was targeted to osteoblasts using the murine 2.3-kb osteoblast-specific type I collagen promoter. In these transgenic mice, bone formation was significantly reduced during postnatal life. Our results demonstrate for the first time that Smurf1 plays a specific role in osteoblast differentiation and bone formation in vivo.

Alkaline Phosphatase↗
PubMed2003

IL-8-mediated cell migration in endothelial cells depends on cathepsin B activity and transactivation of the epidermal growth factor receptor.

Microvascular endothelial cells (HMECs) express both the CXCR1 and the CXCR2, but cell migration is almost entirely mediated by the CXCR2. Similarly, NIH 3T3 cells transfected with the CXCR2 migrated toward IL-8, whereas CXCR1-transfected cells failed to do so. This situation differs from that seen in leukocytes, where chemotaxis is primarily a function of the CXCR1. To define signal transduction pathways that explain this difference in behavior, various inhibitors were used to block cell migration. Apart from inhibitors of phosphatidylinositol 3-kinase, which blocked migration in all cases, inhibition of the epidermal growth factor (EGF) receptor blocked IL-8-mediated cell migration in HMECs and in CXCR2-transfected NIH 3T3 cells, but not in RBL2H3 cells, which do not express an EGFR. Blocking Abs against the EGFR or against heparin-binding EGF-like growth factor similarly blocked IL-8-mediated cell migration and in vitro tubulogenesis in HMECs. Furthermore, inhibition of the EGFR also attenuated focus formation in NIH 3T3 expressing the CXCR2. Immunoprecipitations of the EGFR in HMECs and in NIH 3T3 cells expressing the CXCR2 confirmed that the EGFR was phosphorylated following stimulation with IL-8. However, in contrast to previous reports, e.g., for the thrombin receptor, inhibition of matrix metalloproteases blocked IL-8-mediated cell migration only partially, whereas it was ablated by inhibition of cathepsin B. These results indicate that IL-8-induced transactivation of the EGFR is mediated by the CXCR2 and involves cathepsin B, and that this pathway is important for the migratory and tumorigenic effects of IL-8.

Animals↗
PubMed2003

A rapid and sensitive method for determination of dimethyl benzoylphenyl urea in human plasma by using LC/MS/MS.

Dimethyl benzoylphenyl urea (BPU), a poorly water-soluble benzoylphenyl urea derivative, inhibits tubulin polymerization and causes microtubule depolymerization in vitro with activity against solid tumors. BPU is currently being tested in Phase I clinical trials. A rapid, sensitive and specific method using LC/MS/MS has been developed for the quantitation of BPU in human plasma to perform pharmacokinetic (PK) and pharmacodynamic (PD) studies of BPU administered orally once a week. BPU is extracted from plasma into acetonitrile-n-butylchloride and separated on a Waters X-Terra MS C18 (50 x 2.1 mm, 3.5 microm) column with acetonitrile/water mobile phase (80:20, v/v) containing 0.1% formic acid using isocratic flow at 0.15 ml/min for 5 min. The analyte of interest was monitored by tandem-mass spectrometry with electrospray positive ionization with a cone voltage 15 V for BPU and 30 V for the internal standard, paclitaxel. The detector settings allowed the monitoring of the [MH](+) ion of BPU (m/z 470.3) and the [MH](+) of internal standard paclitaxel (m/z 854.5), with subsequent monitoring of the product ions of BPU (m/z 148.0) and paclitaxel (m/z 286.1). Calibration curves were generated over the range of 0.05-10 ng/ml with values for coefficient of determination of >0.99. The values for precision and accuracy were <20 and < or =15%, respectively. Following administration of BPU 5 mg as a weekly oral dose to a patient with advanced solid tumor malignancies, the maximum plasma concentration was 6.5 ng/ml and concentrations were quantifiable up to 173 h after administration. The lower limit of quantitation (LLOQ) of 0.05 ng/ml allows for successful measurement of plasma concentrations in patients receiving therapy with BPU as a once weekly oral dose.

Gas Chromatography-Mass Spectrometry↗
PubMed2003

Identification, synthesis and bioassay for the metabolites of P6A.

The metabolites Ala-Arg-Pro-Ala-OH, Ala-Arg-Pro-OH, Arg-Pro-Ala-Lys-OH and Pro-Ala-Lys-OH were identified by HPLC/ESI/MS from the in vivo blood of Ala-Arg-Pro-Ala-Lys-OH (P6A) received mice. The in vitro incubation of P6A in the blood of mice the same metabolites were also found by use of the Prep LC System. The protective intermediates of these metabolites were prepared via the solution method using the stepwise synthesis in 77.4, 90, 88, and 80% yield, respectively. After deprotection with catalytic hydrogenation the intermediates were converted into the corresponding sequences Arg-Pro-Ala-Lys-OH, Pro-Ala-Lys-OH, Ala-Arg-Pro-Ala-OH, and Ala-Arg-Pro-OH in 90, 95, 85% and 86% yield, respectively. In the thrombolysis in vivo assay the synthetic Ala-Arg-Pro-Ala-OH, and Ala-Arg-Pro-OH exhibited no activity. On the other hand the thrombolytic activity of Arg-Pro-Ala-Lys-OH was comparable to P6A, and an enhanced thrombolytic activity was observed for Pro-Ala-Lys-OH. In the in vitro fibrinolytic lysis tests the approximate results were obtained and an enhanced activity was also observed for Pro-Ala-Lys-OH. In the euglobulin clot lysis time tests P6A, Arg-Pro-Ala-Lys-OH and Pro-Ala-Lys-OH gave significantly shorter time than that given by UK, demonstrating their fast action.

Animals↗
PubMed2003

Synthesis and bioactivities of nitronyl nitroxide and RGD containing pseudopeptides.

1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetic acid (3), and 1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetyl-RGDS (13), -RGDV (14), -RGDF (15) were synthesized. The ESR measurement gave the same spectroscopy for 3 and 13-15. The NO scavenging tests in vitro, anti-platelet aggregation tests in vitro and the anti-thrombosis assay in vivo indicated that introducing 3 into the N-terminal of RGDS, RGDV and RGDF the corresponding bioactivities for both of 3 and RGD peptides can be remained completely. The present combinations provided a beneficial strategy for simultaneous scavenging NO and anti-thrombosis, and for the use of spin label of RGD peptides in the conformational researches.

Amino Acid Sequence↗
PubMed2003

Structure of pteridine reductase (PTR1) from Leishmania tarentolae.

The protozoan parasites Leishmania utilize a pteridine-reducing enzyme, pteridine reductase (PTR1), to bypass antifolate inhibition. The crystal structure of PTR1 from L. tarentolae has been solved as a binary complex with NADPH at 2.8 A resolution. The structure was solved by molecular-replacement techniques using the recently reported L. major PTR1 structure as a search model. Comparisons of the present structure with the L. major PTR1 allowed us to identify regions of flexibility in the molecule. PTR1 is a member of the growing family of short-chain dehydrogenases (SDR) which share the characteristic Tyr(Xaa)(3)Lys motif in the vicinity of the active site. The functional enzyme is a tetramer and the crystallographic asymmetric unit contains a tetramer with 222 point-group symmetry.

Amino Acid Sequence↗