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Biomedical subjects

Min Yao

Publications and source records attributed to Min Yao.

At least 55 records · Page 3Linked to original sources
PubMed2005

Molecular basis of alanine discrimination in editing site.

AlaX is the homologue of the class II alanyl-tRNA synthetase editing domain and has been shown to exhibit autonomous editing activity against mischarged tRNA(Ala). Here, we present the structures of AlaX from the archaeon Pyrococcus horikoshii in apo form, complexed with zinc, and with noncognate amino acid l-serine and zinc. Together with mutational analysis, we demonstrated that the conserved Thr-30 hydroxyl group located near the beta-methylene of the bound serine is responsible for the discrimination of noncognate serine from cognate alanine, based on their chemical natures. Furthermore, we confirmed that the conserved Gln-584 in alanyl-tRNA synthetase, which corresponds to Thr-30 of AlaX, is also critical for discrimination. These observations strongly suggested conservation of the chemical discrimination among trans- and cis-editing of tRNA(Ala).

Acylation↗
PubMed2005

Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects.

The Escherichia coli chromosome encodes toxin-antitoxin pairs. The toxin RelE cleaves mRNA positioned at the A-site in ribosomes, whereas the antitoxin RelB relieves the effect of RelE. The hyperthermophilic archaeon Pyrococcus horikoshii OT3 has the archaeal homologs aRelE and aRelB. Here we report the crystal structure of aRelE in complex with aRelB determined at a resolution of 2.3 A. aRelE folds into an alpha/beta structure, whereas aRelB lacks a distinct hydrophobic core and extensively wraps around the molecular surface of aRelE. Neither component shows structural homology to known ribonucleases or their inhibitors. Site-directed mutagenesis suggests that Arg85, in the C-terminal region, is strongly involved in the functional activity of aRelE, whereas Arg40, Leu48, Arg58 and Arg65 play a modest role in the toxin's activity.

Antitoxins↗
PubMed2005

Structure of the type I L-asparaginase from the hyperthermophilic archaeon Pyrococcus horikoshii at 2.16 angstroms resolution.

The crystal structure of the L-asparaginase from the hyperthermophilic archaeon Pyrococcus horikoshii (PhA) was determined by the multiwavelength anomalous diffraction (MAD) method and was refined to a resolution of 2.16 angstroms with a crystallographic R factor and free R factor of 21.1 and 25.3%, respectively. This is the first report of the three-dimensional structure of a type I L-asparaginase. These enyzmes are known as cytosolic L-asparaginases with lower affinities for substrate than the type II L-asparaginases. Although the overall fold of PhA was closely related to the structure of the well characterized type II L-asparaginase, structural differences were also detected. PhA forms a homodimer that corresponds to half the homotetramer of type II L-asparaginases. Structure comparison at the active site reveals that most catalytic residues are conserved except for two residues that recognize the amino group of the substrate. Additionally, a remarkable structural difference is found in the so-called 'active-site flexible loop'. In PhA this loop is stabilized by beta-hairpin formation and by elaborate interactions with the type-I-specific alpha-helical region derived from the other subunit forming the PhA dimer. The flexible loop of the type II enzyme is considered to serve as a mobile gate to the active site. Therefore, the loop stabilization observed in the PhA structure may cause limitation of the access of the substrate to the active site.

Amino Acid Sequence↗
PubMed2005

Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer.

PURPOSE: To determine whether the nonselective and relatively inexpensive nonsteroidal anti-inflammatory drug ibuprofen would be effective in inhibiting colorectal cancer and might improve mortality in a mouse model. EXPERIMENTAL DESIGN: The effects of ibuprofen on tumor growth inhibition and animal survival have been examined in both mouse and human colorectal cancer tumor models. Angiogenesis was measured by in vitro endothelial cell tube formation and immunohistochemistry. RESULTS: Ibuprofen significantly inhibited cell proliferation in mouse (MC-26) and human (HT-29) colorectal cancer cell lines. In vitro angiogenesis assays also indicated that ibuprofen decreased both cell proliferation and tube formation. The administration of chow containing 1,360 ppm ibuprofen, which achieved an average plasma concentration of ibuprofen lower than the peak level achieved in humans at therapeutic doses, inhibited tumor growth by 40% to 82%. Fewer liver metastases were found in the ibuprofen group compared with the control group. In combination therapy with the standard antineoplastic agents, 5-fluorouracil, or irinotecan (CPT-11), tumor volumes in the groups with ibuprofen +/- CPT-11 or 5-fluorouracil were smaller than in the control group. Ibuprofen was similar to the cyclooxygenase-2 selective inhibitor rofecoxib in its ability to suppress tumor growth and improve overall survival. CONCLUSIONS: Ibuprofen, in part by modulating tumor angiogenesis, decreases both tumor growth and metastatic potential in mice. The ibuprofen doses were in the low range of therapeutic human plasma concentrations. Ibuprofen potentiates the antitumor properties of CPT-11 and improves survival of mice without increasing gastrointestinal toxicity.

Animals↗
PubMed2005

Crystallization and preliminary crystallographic analysis of the cellulose biosynthesis-related protein CMCax from Acetobacter xylinum.

The cellulose biosynthesis-related protein CMCax from Acetobacter xylinum was overexpressed in Escherichia coli, purified and crystallized. Single crystals of selenomethionine (SeMet) substituted CMCax were obtained by the hanging-drop vapour-diffusion method at 293 K, primarily using polyethylene glycol 4000 as a precipitant. The crystals belong to the primitive hexagonal space group P6(1) or P6(5), with unit-cell parameters a = b = 89.1, c = 94.2 A. The predicted Matthews coefficient (VM) value is 3.0 A3 Da(-1) for one CMCax monomer in the asymmetric unit. A single-wavelength anomalous dispersion (SAD) data set was collected to a resolution of 2.3 A using synchrotron radiation.

Bacterial Proteins↗
PubMed2005

Crystallization and preliminary X-ray analysis of alpha-xylosidase from Escherichia coli.

Glycoside hydrolases have been implicated in many biological processes. To date, they have been classified into 93 glycoside hydrolase (GH) families based on amino-acid sequence similarity. alpha-Xylosidase from Escherichia coli belongs to GH family 31 and catalyzes the release of alpha-xylose from the non-reducing terminal side of alpha-xyloside. Single crystals of alpha-xylosidase have been grown by vapour diffusion at 293 K from 10%(w/v) PEG 20K, 2%(v/v) 2-propanol, 2%(v/v) glycerol and 0.1 M 2-morpholinoethanesulfonic acid pH 5.5. These crystals belong to space group P2(1)2(1)2(1) and X-ray diffraction data were collected to a resolution of 2.75 A. Crystals of selenomethionyl-substituted alpha-xylosidase were also obtained, which diffracted to at least 3.0 A. Based on the value of VM, the asymmetric unit in these crystals was assumed to contain six molecules.

Escherichia coli↗
PubMed2005

Long-term quality of life for surgical and nonsurgical treatment of head and neck cancer.

OBJECTIVE: To compare the long-term, health-related quality-of-life outcomes in patients with advanced head and neck cancer (HNC) treated with surgery and postoperative radiation therapy (SRT) or concurrent chemotherapy and radiation therapy (CRT). DESIGN: Matched-pair study comparing patients with advanced HNC treated with SRT or CRT at least 12 months after treatment. Patients completed 2 validated surveys addressing HNC-specific outcomes and depressive symptoms and provided information on employment and tobacco and alcohol use. Results for the 2 groups were compared using paired-sample t test and chi2 analysis. SETTING: University-based study. PATIENTS: Patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, and larynx who underwent SRT or received CRT. MAIN OUTCOME MEASURES: Head and neck cancer-specific health-related quality of life from the Head and Neck Cancer Inventory and level of depressive symptoms from the Beck Depression Inventory. RESULTS: The matching process resulted in 27 patients in each treatment group. The HNC-specific domain scores (with higher scores representing better outcomes) for CRT vs SRT were eating, 37.8 vs 40.8 (P = .69); speech, 65.1 vs 56.0 (P = .23); aesthetics, 80.3 vs 69.2 (P = .14); and social disruption, 69.7 vs 70.6 (P = .90). Overall health-related quality of life was 64.0 with SRT and 55.0 with CRT (P = .142). For the Beck Depression Inventory (with higher scores representing worse outcomes), patients who underwent SRT had a mean score of 9.6 compared with 11.6 for patients who received CRT (P = .42). CONCLUSION: As nonsurgical means of treating HNC have become more aggressive and surgical techniques have become more focused on function preservation and rehabilitation, the overall health-related quality of life resulting from these different approaches is similar.

Combined Modality Therapy↗
PubMed2005

Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice.

Vitamin D deficiency has been associated with increased risk of colon cancer in epidemiologic and prospective clinical studies. In vitro and in vivo studies demonstrated that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its analogs inhibit colon cancer cell proliferation. Few studies have evaluated the effect of vitamin D deficiency on the development and growth of colon cancer. To assess the antiproliferative effects of 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3 in vitro, we cultured MC-26 (a colon cancer cell line) in the presence of 25(OH)D3 and 1,25(OH)2D3 and performed [3H]thymidine incorporation. The proliferation of MC-26 was significantly inhibited by both 25(OH)D3 and 1,25(OH)2D3. To determine the effect of vitamin D deficiency on colon cancer proliferation, Balb/c mice were rendered vitamin D deficient by feeding them a vitamin D-deficient diet for 3 mo. A group of vitamin D-sufficient mice was given the same diet with supplemental vitamin D. The mice were injected with MC-26 colon cancer cells and the tumors were measured daily for 20 d. Vitamin D-sufficient mice had 40% smaller tumors than vitamin D-deficient mice. The tumors were evaluated for mRNA expression of the vitamin D receptor (VDR) and 25-hydroxvitamin D-1alpha-hydroxylase (1alpha-OHase) by quantitative RT-PCR. The expression of the mRNA for the VDR and the 1alpha-OHase was 37- and 6-fold higher, respectively, in the vitamin D-sufficient mice compared with the vitamin D-deficient mice. We conclude that vitamin D deficiency enhances the growth of colon cancer in mice. The tumor expression of VDR and 1alpha-OHase indicates possible autocrine/paracrine cell growth regulation by vitamin D.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2005

Merkel cell carcinoma: two case reports focusing on the role of fluorodeoxyglucose positron emission tomography imaging in staging and surveillance.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare skin neuroendocrine carcinoma frequently occurring in the head and neck area. It is known for being a locally aggressive disease with a high incidence of regional and distant metastases. Accurate initial staging and close surveillance are critical in the management of the disease. METHODS AND RESULTS: Two cases of MCC are reported in which fluorine-18-fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been beneficial in directing management and predicting clinical course. Pretreatment FDG PET scans detected metastatic disease in subcentimeter lymph nodes that were not appreciated in initial computed tomography images. Posttreatment FDG PET scans predicted response to therapy with the level of FDG uptake correlating in both areas of complete response to treatment and areas of residual diseases. Finally, FDG PET imaging also detected the progression of the disease after initial treatment. CONCLUSION: FDG PET imaging is a very sensitive modality in staging, assessment of treatment response, and surveillance of MCC. Because of the rarity of MCC, multicenter study is warranted to accumulate enough cases to determine the sensitivity and specificity of FDG PET in staging and surveillance of MCC, and the impact on the management and treatment outcome.

Aged↗
PubMed2005

Preparation, crystallization and preliminary X-ray diffraction analysis of PH1948, predicted RNA methyltransferase from Pyrococcus horikoshii.

RNA methyltransferase is responsible for transferring methyl and resulting in methylation on the bases or ribose ring of RNA, which existed widely but mostly remains an open question. A recombinant protein PH1948 predicting RNA methyltransferase from Pyrococcus horikoshii OT3 has been crystallized. The crystals of selenomethionyl PH1948 belong to space group C2, with unit-cell parameters a=207.0 A, b=43.1 A, c=118.2 A, b=92.1 degrees , and diffract X-rays to 2.2 A resolution. The V(M) value was determined to be 2.8 A3/Da, indicating the presence of four protein molecules in the asymmetric unit.

Crystallization↗
PubMed2005

[Coronary angiography by transradial approach with 5F universal catheter].

OBJECTIVE: To probe the efficacy and feasibility of the transradial approach for diagnostic coronary angiography with 5F universal catheter. METHODS: Transradial coronary angiography was performed in 3094 consecutive patients, 2396 men and 698 women, aged 30 - 81 years, mean age (56.1 +/- 9.8) years, from July 2000 to April 2004. Patients were divided into 5F improved Terumo catheter group (improved Terumo group, n = 985), 5F universal Terumo catheter group (Terumo group, n = 1024) and 5F universal Medtronic catheter group (Medtronic group, n = 1085). The procedure success rate, duration of operation and fluoroscopy between groups were compared. RESULTS: The procedure success rate was 98.4% in improved Terumo group, 98.0% in Terumo group, and 96.0 % in Medtronic group, respectively. The success rate was higher in improved Terumo group than in Medtronic group (P < 0.05). The average duration of operation and fluoroscopy in improved Terumo group was (17.9 +/- 5.8) min and (4.8 +/- 1.8) min, in Terumo group was (18.2 +/- 5.5) min and (5.0 +/- 1.7) min, but (21.1 +/- 7.2) min and (5.2 +/- 1.9) min in Medtronic group. There were significant differences among group (P < 0.05). CONCLUSIONS: (1) Transradial coronary angiography with small diameter universal catheter is safe and easy to perform with a higher success rate and allow earlier patient ambulation, and should be strongly encouraged and recommended. (2) Option of angiographic catheter plays a key role in the safety, efficacy and quality of transradial coronary angiography. Seemingly, the improved Terumo group was excellent and shoud be popularized.

Adult↗
PubMed2005

[The influence of diabetes mellitus on the procedural and in-hospital outcomes after selective percutaneous coronary intervention].

OBJECTIVE: To compare the procedural and in-hospital outcomes in a large series of diabetic and non-diabetic patients undergoing selective percutaneous coronary intervention (PCI) and to evaluate the influence of diabetes mellitus on the procedural and in-hospital outcomes. METHODS: 1294 consecutive patients underwent selective PCI from January to December 2002 in this institution were analyzed retrospectively. Baseline clinical, in-lab and in-hospital outcome information were recorded. Rates of procedural success, device success and clinical success were analyzed and logistic regression was performed to model the association between diabetes status and outcomes. RESULTS: Two hundred and sixty-nine patients (20.8%) complicated with diabetes. Type C lesion, double and triple vessel diseases were more prevalent in diabetics than those in non-diabetics. The pre-PCI diameter stenosis of diabetics was significantly more severe than that of non-diabetics (91.00 +/- 6.62 vs 89.81 +/- 6.64, P < 0.01). The balloon length, maximum balloon diameter and maximum balloon inflation pressure, maximum inflation duration were larger in diabetics than those in non-diabetics [(17.07 +/- 6.31) mm vs (16.07 +/- 7.28) mm, (2.30 +/- 1.11) mm vs (2.12 +/- 0.94) mm, (9.86 +/- 4.40) atm vs (9.05 +/- 4.75) atm, (20.94 +/- 14.69) s vs (18.26 +/- 14.65) s, respectively, P < 0.05]. The stent diameter was smaller in diabetics than that in non-diabetics [(3.15 +/- 0.47) mm vs (3.23 +/- 0.43) mm, P < 0.05]. The procedural success rate showed no significant difference between two groups (89.6% vs 90.3%, P > 0.05). But a higher incidence of acute/subacute stent thrombosis was observed in diabetics compared with that in non-diabetics (1.9% vs 0.5%, P < 0.05). The rate of clinical success was similar between diabetics and non-diabetics (99.3% vs 99.2%, P > 0.05). Diabetes was not an independent predictor of acute outcomes in the regression model. CONCLUSIONS: A higher incidence of acute/subacute stent thrombosis was observed in diabetics. The incidence of procedural and in-hospital major adverse cardiac events and the rate of clinical success were similar between diabetics and non-diabetics. Diabetes was not an independent predictor of in-hospital outcomes after selective PCI.

Aged↗