Search PubMed⌕ Search

Biomedical subjects

Wei Yang

Publications and source records attributed to Wei Yang.

At least 73 records · Page 4Linked to original sources

[Adeno-associated viral gene transfer of SERCA2a improves heart function in chronic congestive heart failure rats].

OBJECTIVE: To study the therapy effect of adeno-associated viral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) on chronic congestive heart failure (HF) in 30 days, and the possible mechanism of the therapy effect. METHODS: The rats were divided into four groups: control group, HF group, Group HF + EGFP, and Group HF + SERCA2a. HF rats were obtained by creating descending aortic constriction. 0.9% sodium chloride solution, recombinant adeno-associated virus carrying enhanced green fluorescent protein gene (rAAV2.eGFP) and recombinant adeno-associated virus carrying SERCA2a gene (rAAV2.SERCA2a), were respectively delivered to pericardium of HF rats in different groups by intrapericardial injection with a trans-diaphragmatic approach. 30 days after gene transfer, hemodynamic parameters, SERCA2a protein expression and SERCA2a activity were analyzed. The proteome difference from rat hearts between Groups HF + SERCA2a and HF was detected by expression proteomics. Electrophoretic separation and quantitation of cardiac myosin heavy chain isoforms of hearts in different groups were performed at 30 days. RESULTS: At 30 days, left ventricular function improved significantly in HF rats infected with rAAV2.SERCA2a (LVSP 146.52 +/- 13.86 vs 97.91 +/- 12.13, LVEDP 7.88 +/- 2.88 vs 21.15 +/- 3.57, LV +dp/dt 11 206.16 +/- 1730.11 vs 5948.93 +/- 1283.43, LV -dp/dt -8249.54 +/- 1076.09 vs -4497.50 +/- 652.12; P < 0.05). The recovered cardiac function in Group HF + SERCA2a rats was comparable to control rats, and had lower LV-weight/Body-weight ratio (2.46 +/- 0.17 vs 2.71 +/- 0.24, P < 0.05). Overexpression of SERCA2a increased both the protein content (0.39 +/- 0.11 vs 1.11 +/- 0.18, P < 0.05) and activity (228.62 +/- 25.11 vs 82.55 +/- 14.13, P < 0.05) up to nonfailing levels. Expressions of some energy metabolic enzymes in hearts of Group HF + SERCA2a were much higher than those of HF group. They included creatine kinase-muscle, enolase beta, fructose-bisphosphate aldolase, mitochondrial H(+)-ATP synthase alpha subunit, electron transfer flavoprotein alpha-subunit, H(+)-transporting ATP synthase and heart fatty acid binding protein. Downregulation of alpha-MHC and upregulation of beta-MHC in failing hearts were observed. Gene transfer of SERCA2a could increase the expression of alpha-MHC [(74.48 +/- 3.74)% vs (53.57 +/- 2.30)%, P < 0.05], and decrease the expression of beta-MHC [(25.52 +/- 3.74)% vs (46.43 +/- 2.30)%, P < 0.05] in HF rats. The expression profiles of alpha-MHC and beta-MHC and the ratio of alpha-MHC/beta-MHC were similar to those in controls. CONCLUSIONS: Adeno-associated viral gene transfer of SERCA2a can enhance SERCA2a functions, maintain calcium homeostasis, improve cardiac energy metabolism, and normalize the expression of cardiac myosin heavy chain isoforms in HF rats. As a result, the ventricular systolic and diastolic functions can be improved significantly, and the hypertrophy of the heart may be reduced in clinic. Adeno-associated viral gene transfer of SERCA2a demonstrated good therapy effects on HF rats.

Adenoviridae↗

[Chicken genome project and its application in genetic research].

Chicken is an important model organism for studying all sorts of biological problems due to its unique biological features. Two strains of chicken, the egg-laying layer and meat-producing broiler, which were generated from selective breeding, come to be ideal models for understanding the molecular mechanisms underlying different phenotypes. The Chicken Genome Project provides a large amount of information for research using chicken as the model. This review summarizes the development of the Chicken Genome Project, as well as the strategies for researching the quantitative traits of different chicken strains using the information of the Chicken Genome. We also give a perspective of the developmental and genetic studies that can be conducted using the chicken as a model organism as well as using its genomic information.

Animals↗

[Clinical observation on acupuncture combined with medicine for treatment of infantile febrile convulsion].

OBJECTIVE: To explore an effective therapy for treatment of infantile febrile convulsion. METHODS: Seventy infants of febrile convulsion were randomly divided into two groups, a combined acupuncture and drug group (n = 36) were treated with Xingnao Kaiqiao needling method with Shuigou (GV 26) selected as main combined with intramuscular injection of luminal and intravenous perfusion of diazepam; and a drug group (n = 34) treated with simple intramuscular injection of luminal and intravenous perfusion of diazepam. Their therapeutic effects, the time of inducing the stopping convulsion, and the recurrence rate were investigated. RESULTS: The total effective rate was 86.1% in the combined acupuncture and drug group, better than 79.4% in the drug group (P<0.05), and the time of inducing the stopping convulsion in the combined acupuncture and drug group was shorter than that in the drug group (P<0.01), and the recurrence rate in the combined group was lower than that in the drug group (P<0.05). CONCLUSION: Acupuncture combined with intramuscular injection of luminal and intravenous perfusion of diazepam is an effective and safe method for febrile convulsion.

Acupuncture Points↗

[Clinical observation on the method for nourishing blood and moisturizing eye on xerophthalmia].

OBJECTIVE: To observe therapeutic effect of the method for nourishing blood and moisturizing eye on xerophthalmia. METHODS: Fifty-one cases of xerophthalmia were randomly divided into a treatment group and a control group. The treatment group were treated by acupuncture, moxibustion with Chinese medicine, and auricular point pressing, and the control group were treated with dripping of artificial tears. Local symptoms of eyes, tear secretion amount (Schirmer method) and BUT were observed before and after treatment. RESULTS: The total effective rate of 88.5% in the treatment group was better than 52.0% in the control group (P<0.05). CONCLUSION: The method for nourishing blood and moisturizing eye is a better therapy for xerophthalmia.

Acupuncture↗

[Chronic effects of transmyocardial laser revascularization combined with off-pump coronary artery by pass (OPCAB) compared with OPCAB alone in patients with ischemic heart disease: a prospective multicenter follow-up study].

OBJECTIVE: To approach the long term safety and efficacy of transmyocardial laser revascularization (TMLR, holmium: YAG) combined with off-pump coronary artery bypass (OPCAB) compared with OPCAB alone in patients with ischemic cardiac disease. METHODS: Between 1999 and 2005, 80 patients with diffusely diseased target vessels from two centers in Beijing were enrolled to the study and randomized to receive either TMLR/OPCAB (n = 40) or OPCAB (n = 40) operation. Baseline demographics and operative characteristics were similar between groups. Follow-up (mean 3.4 +/- 1.7 years) included CCS angina class and NYHA classification assessments, 6 minutes walking test (6MWT) and echocardiography. RESULTS: Perioperative mortality was 5% in both groups. No death occurred during follow up. At the end of follow-up, patients at both groups experienced significant improvement on angina score compared with baseline, and angina score was also significantly lower (1.21 +/- 0.42 vs. 1.57 +/- 0.87, P = 0.03) and 6MWT-distance significantly increased (518.0 +/- 65.5 m vs. 473.8 +/- 65.8m, P = 0.006) in OPCAB/TMLR group than that in the OPCAB group. Fewer patients developed recurrent severe angina and received re-CABG/PCI in OPCAB/TMLR group than that in the OPCAB (1 vs. 6 cases, P = 0.113). NYHA and LVEF were similar between the groups at the end of follow up. CONCLUSION: Our study showed that the addition of TMLR to OPCAB is superior in improving angina and exercise tolerance, but there is no further improvement in cardiac function compared to OPCAB alone.

Aged↗

[Application of contrast-enhanced ultrasonography in selecting indication of radiofrequency ablation among hepatocellular carcinoma patients].

OBJECTIVE: To evaluate the clinical value of contrast-enhanced ultrasound (CEUS) in selection of the patients with hepatocellular carcinoma (HCC) indicated to radiofrequency ablation (RFA). METHODS: 164 patients with HCC, 121 males and 43 females, aged 52.4 (38-72), who asked for RFA were randomly divided into 2 groups: 81 patients undergoing CEUS before RFA (CEUS Group), and 83 patients not undergoing CEUS before RFA (Control Group). There were not significant differences in the TNM staging, liver function Child-Pugh classing, and average tumor size between the 2 groups. Follow-up by conventional ultrasonography, enhanced CT and/or enhanced ultrasonography was conducted for 6-36 months. RESULTS: Nine of the 81 patients in CEUS Group (11.8%) were determined by CEUS as unsuitable for RFA; 5 of the 9 patients had more than 5 lesions, 2 of the 9 patients had lesions > 8 cm in diameter, and the tumor had invaded 2 large vessels or intestine in 2 of the 9 patients. The other 72 patients in CEUS Group, with 101 lesions, underwent RFA after CEUS. CEUS discovered 12 lesions < or = 1.7 cm that had not been discovered by conventional ultrasonography and CT in 8 patients, 3 of which were patients with cirrhosis undergoing follow-up, and 2 of which were HCC patients undergoing follow-up after treatment. Of these 8 patients, 3 had 7 newly discovered satellite lesions around the main lesions. The successful rates of CEUS Group and Control Group were 95.0% and 89.6% respectively (P > 0.05). The distant recurrence rate of Control Group was 22.9%, significantly higher than that of CEUS Group (9.7%, P < 0.05). CONCLUSION: Helping find minute tumors, CEUS is useful in selecting HCC patients suitable for RFA, thus decreasing the intrahepatic recurrence after RFA.

Adult↗

High mechanical index post-contrast ultrasonography improves tissue structural display of hepatocellular carcinoma.

BACKGROUND: The advent of second generation agent-SonoVue and low mechanical index real-time contrast enhanced ultrasonography (CEUS) imaging have been shown to improve the diagnostic performance of ultrasonography in hepatocellular carcinoma (HCC). But no report has described the effect of high mechanical index (MI) post-CEUS. This study aimed to investigate the value of post-CEUS in displaying tissue structures of HCC. METHODS: Seventy-six HCCs in 65 patients were included in the study. Each patient underwent three scans, high-MI (MI: 0.15-1.6) pre-contrast ultrasound, low-MI (MI: 0.04-0.08) CEUS with contrast agent SonoVue, and high-MI post-contrast ultrasound, which was performed within 3 minutes after CEUS. The size, boundary, echogenicity, internal echotexture and posterior acoustic enhancement of the HCCs in the conventional scans before and after CEUS were evaluated. According to pathological evidence, diagnosis rates of pre-contrast, CEUS and post-contrast scans were determined and compared. The potential mechanism of post-contrast ultrasound imaging was also discussed. RESULTS: Compared with pre-contrast, post-contrast ultrasound showed improvement in image quality in most HCCs: twenty-six (34.2%) more lesions showed well defined margins and fourteen (18.4%) more nodules showed halo sign; twenty-three (30.3%) lesions demonstrated enlarged in sizes; changes in echogenicity were seen in 30 lesions (39.5%); eighteen (23.7%) more lesions showed heterogenecity and 20 (26.3%) more lesions showed "mosaic" or "nodule-in-nodule" sign; twelve (15.8%) more lesions showed posterior acoustic enhancement. Post-contrast ultrasound showed increased diagnostic accuracy of 93.4% (71/76), compare with 88.2% (67/76) of CEUS alone. CONCLUSIONS: High-MI post-contrast ultrasound utilizes harmonic signals during the rupture of microbubbles, and significantly improves the display of echo-characteristics of HCCs in ultrasound images, which adds diagnostic values for CEUS. Post-contrast ultrasound could play an important role in tissue characterization, and may be included in CEUS protocols.

Adult↗

[Long term (5 years) outcome of radiofrequency ablation for hepatocellular carcinoma in 256 cases].

A total of 267 patients with hepatocellular carcinoma underwent ultrasound-guided radiofrequency ablation (RFA) in Peking University School of Oncology between 1999 and 2005 (421 RFA sessions). Among them, 254 patients were candidates for RFA treatment and the selective criteria were: (1) the greatest diameter of tumor 5 cm, respectively. According to tumor size, shape and location, we adopted a defined treatment strategy, which consisted of a mathematical protocol, an individualized protocol and adjunctive measures. And several methods were also used to prevent and deal with complications in tumors with different features. In this series the tumor complete necrosis rate (CR)was 95.2% (356/374 tumors). It was higher in 3.5 cm tumors with a CR of 91.3% (156/171 tumors). CR were 95.6% (44/46 tumors) for tumors near the gallbladder, 92.9%(79/85 tumors) for tumors near the diaphragm, 90.9%(40/44 tumors) for tumors near the gastrointestinal tract, 91.2% (31/34 tumors) for tumors near large vessel. In a follow-up period of 2-69 months, the local recurrence rates were 11.7% for HCC and 12.5% for recurrent HCC. The incidence of complications was 2.4% (10/409 sessions), including intraperitoneal hemorrhage (n=2), biliary duct stricture (n=1), hemothorax (n=1), bowel perforation (n=1) and needle tract seeding (n=5). Of these cases, only 3 required operation and the mortality related to RFA was zero in this series. We used Kaplain-Meier method and log-rank test to estimate and compare the survival rate. The 1-, 3-, and 5-year survival rates after RFA were 83.3%, 66.9%, 41.2%, respectively for all HCC patients and 74.6%, 41.3%, 33.6%, respectively for recurrent HCC. Survivals based on TNM stage, Child-Pugh grade, tumor number and tumor size are shown in Table 1. In conclusion, RFA with standard protocol has evolved as a minimally invasive local treatment that could achieve satisfactory outcomes for small liver tumors, and has become an effective and relatively safe alternative for the treatment of advanced tumors and recurrent tumors, which are not suitable for traditional therapy. RFA has broaded the treatment threshold for hepatic malignancies and might become one of the regular treatment methods in focal liver tumor and find wide application.

Adult↗

Heritable alteration in DNA methylation pattern occurred specifically at mobile elements in rice plants following hydrostatic pressurization.

Intrinsic DNA methylation pattern is an integral component of the epigenetic network in many eukaryotes. Exploring the extent to which DNA methylation patterns can be altered under a specific condition is important for elucidating the biological functions of this epigenetic modification. This is of added significance in plants wherein the newly acquired methylation patterns can be inherited through organismal generations. We report here that DNA methylation patterns of mobile elements but not of cellular genes were specifically altered in rice plants following hydrostatic pressurization. This was evidenced by methylation-sensitive gel-blot analysis, which showed that 10 out of 10 studied low-copy transposons and retrotransposons manifested methylation alteration in at least one of the 8 randomly chosen pressure-treated plants, whereas none of the 16 studied low-copy cellular genes showed any change. Both gel-blotting and genome-wide fingerprinting indicated that the methylation alteration in mobile elements was not accompanied by a general genetic instability. Progeny analysis indicated retention of the altered methylation patterns in most progeny plants, underscoring early occurrence of the alterations, and their faithful epigenetic inheritance.

Cytosine↗

Endothelial nitric oxide synthase (NOS3) genetic variants, maternal smoking, vitamin use, and risk of human orofacial clefts.

Orofacial clefts have been associated with maternal cigarette smoking and lack of folic acid supplementation (which results in higher plasma homocysteine concentrations). Because endothelial nitric oxide synthase (NOS3) activity influences homocysteine concentration and because smoking compromises NOS3 activity, genetic variation in NOS3 might interact with smoking and folic acid use in clefting risk. The authors genotyped 244 infants with isolated cleft lip with or without cleft palate (CL/P), 99 with isolated cleft palate, and 588 controls from a California population-based case-control study (1987-1989 birth cohort) for two NOS3 polymorphisms: A(-922)G and G894T. Analyses of gene-only effects for each polymorphism revealed a 60% increased risk of CL/P among NOS3 A(-922)G homozygotes (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.6). There was some evidence for higher risk of CL/P with maternal periconceptional smoking in infants with an NOS3 -922G allele (for homozygotes, OR = 2.5, 95% CI: 1.2, 5.6) but not in those with an 894T allele. For CL/P risk, odds ratios were over 4 among mothers who smoked, who did not use vitamins, and whose infants had at least one variant allele for each NOS3 polymorphism (for A(-922)G, OR = 4.6, 95% CI: 2.1, 10.2; for 894T, OR = 4.4, 95% CI: 1.8, 10.7). No similar patterns were observed for risk of cleft palate.

Adult↗

An egg apparatus-specific enhancer of Arabidopsis, identified by enhancer detection.

Despite a central role in angiosperm reproduction, few gametophyte-specific genes and promoters have been isolated, particularly for the inaccessible female gametophyte (embryo sac). Using the Ds-based enhancer-detector line ET253, we have cloned an egg apparatus-specific enhancer (EASE) from Arabidopsis (Arabidopsis thaliana). The genomic region flanking the Ds insertion site was further analyzed by examining its capability to control gusA and GFP reporter gene expression in the embryo sac in a transgenic context. Through analysis of a 5' and 3' deletion series in transgenic Arabidopsis, the sequence responsible for egg apparatus-specific expression was delineated to 77 bp. Our data showed that this enhancer is unique in the Arabidopsis genome, is conserved among different accessions, and shows an unusual pattern of sequence variation. This EASE works independently of position and orientation in Arabidopsis but is probably not associated with any nearby gene, suggesting either that it acts over a large distance or that a cryptic element was detected. Embryo-specific ablation in Arabidopsis was achieved by transactivation of a diphtheria toxin gene under the control of the EASE. The potential application of the EASE element and similar control elements as part of an open-source biotechnology toolkit for apomixis is discussed.

Arabidopsis↗

Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications.

AIM: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic malignant tumor and the relevant complications. METHODS: A total of 338 patients with 763 hepatic tumors underwent ultrasound-guided RFA (565 procedures). There were 204 cases of hepatic cellular carcinoma (HCC) with 430 tumors, the mean largest diameter was 4.0 cm. Of them, 48 patients (23.5%) were in stages I-II (UICC Systems) and 156 (76.5%) in stages III-IV There were 134 cases of metastatic liver carcinoma (MLC), with 333 metastases in the liver, the mean diameter was 4.1 cm, the liver metastases of 96 patients (71.6%) came from gastrointestinal tract. Ninety-three percent of the 338 patients were treated using the relatively standard protocol. Crucial attention must be paid to monitor the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structures injury in time. The tumors were considered as ablated completely, if no viability was found on enhanced CT within 24 h or at 1 mo after RFA. These patients were followed up for 3-57 mo. RESULTS: The ablation success rate was 93.3% (401/430 tumors) for HCC and was 96.7% (322/333 tumors) for MLC. The local recurrence rate for HCC and MLC was 7.9% (34/430 tumors) and 10.5% (35/333 tumors), respectively. A total of 137 patients (40.5%) underwent 2-11 times of repeated ablations because of tumor recurrence or metastasis. The 1st, 2nd, and 3rd year survival rate was 84.6%, 66.6%, and 63.1%, respectively; the survival rate from 48 patients of I-II stage HCC was 93.7%, 80.4%, and 80.4%, respectively. The major complication rate in this study was 2.5% (14 of 565 procedures), which consisted of 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages, and 1 skin burn. CONCLUSION: RFA, as a minimally invasive local treatment, has become an effective and relatively safe alternative for the patients of hepatic malignant tumor, even of advanced liver tumor, tumor recurrence, and liver metastases. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.

Adult↗

A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida.

Folate binding protein 1 (Folr1) knockout mice with low maternal folate concentrations have been shown to be excellent animal models for human folate-responsive neural tube defects (NTDs). Previous studies using the Folr1 knockout mice revealed that maternal folate supplementation up-regulates the expression of the PCMT1 gene in Folr1 nullizygous neural tube tissue during neural tube closure. PCMT1 encodes the protein repair enzyme l-isoaspartate (d-aspartate) O-methyltransferase (PIMT) that converts abnormal d-aspartyl and l-isoaspartyl residues to the normal l-aspartyl form. PIMT is known to protect certain neural cells from Bax-induced apoptosis. Pcmt1-deficient mice present with abnormal AdoMet/AdoHcy homeostasis. We hypothesized that a known functional polymorphism (Ile120Val) in the human PCMT1 gene is associated with an increased risk of folate-responsive human NTDs. A case-control study was conducted to investigate a possible association between this polymorphism and risk of spina bifida. Compared to the Ile/Ile and Ile/Val genotypes, the homozygous Val/Val genotype showed decreased risk for spina bifida (adjusted odds ratio=0.6, 95% confidence interval: 0.4-0.9). Our results showed that the Ile120Val polymorphism of PCMT1 gene is a genetic modifier for the risk of spina bifida. Val/Val genotype was associated with a reduction in risk for spina bifida.

Adult↗

A structure-based model for the synthesis and hydrolysis of ATP by F1-ATPase.

Many essential functions of living cells are performed by nanoscale protein motors. The best characterized of these is F(o)F1-ATP synthase, the smallest rotary motor. This rotary motor catalyzes the synthesis of ATP with high efficiency under conditions where the reactants (ADP, H2PO4(-)) and the product (ATP) are present in the cell at similar concentrations. We present a detailed structure-based kinetic model for the mechanism of action of F1-ATPase and demonstrate the role of different protein conformations for substrate binding during ATP synthesis and ATP hydrolysis. The model shows that the pathway for ATP hydrolysis is not simply the pathway for ATP synthesis in reverse. The findings of the model also explain why the cellular concentration of ATP does not inhibit ATP synthesis.

Adenosine Triphosphate↗

[Intraperitoneal hemorrhage during and after percutaneous radiofrequency ablation of hepatic tumors: reasons and management].

BACKGROUND: Intraperitoneal hemorrhage is one of the most common complications of radiofrequency (RF) ablation of hepatic tumors. This study was designed to investigate the reason and management of intraperitoneal hemorrhage occurred during or after percutaneous RF ablation of hepatic tumors. METHODS: Three hundred and fifty-six patients with hepatic tumors have been treated at 592 procedures of ultrasound guided RF ablation. Intraperitoneal hemorrhage occurred in 5 patients (0.8%). The reasons and management of intraperitoneal hemorrhage in these 5 cases were retrospectively analyzed. RESULTS: Two patients with liver metastasis and one hepatocellular carcinoma (HCC) patient suffered from hemorrhage during the RF treatment. Two patients with recurrent HCC after surgery developed hemorrhage 20 minutes or 4 hours after RF treatment. One case of hemorrhage was due to the inappropriate electrode positioning induced liver laceration while treating a 1 cm liver metastasis near the liver capsule. One was due to the injury of a small vessel by the RF needle in another liver metastasis patient. Three cases were due to tumor rupture with two cases induced by cough or position change after treating large protruding HCC lesions. Four (80%) of the 5 cases of hemorrhage were rapidly identified by ultrasound. The causes and sites of bleeding during the RF treatment in three cases were confirmed through ultrasound, which were successfully treated using RF coagulation to achieve hemostasis of the bleeding site. Two patients with post-ablation hemorrhage recovered in one hour and 24 hours, respectively after given blood transfusion and other conservative measures. No surgical intervention was required. Two patients died of wide spread metastasis 23 - 36 months afterwards and the other three patients have lived for 18 - 25 months to date. CONCLUSIONS: It is important to perform close monitoring during and after RF ablation in order to identify intraperitoneal hemorrhage in time. RF ablation of the bleeding sites was a simple and effective management when the bleeding site could be confirmed by ultrasound. The hemorrhage due to the rupture of large and protruding liver tumors could be serious and should be considered as contraindication for RF treatment.

Adult↗

[Early diagnosis of small hepatocellular carcinoma by new contrast-enhanced ultrasound technique].

OBJECTIVE: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS) enhancement patterns of hepatocellular carcinoma (HCC) smaller than 2 cm. METHODS: From 392 cases with focal liver lesions undergoing CEUS with SonoVue and Contrast Tuned Imaging (CnTI) technique, thirty six cirrhotic patients with thirty eight HCCs with histopathological diagnosis were retrospectively analyzed in this study. Surgery or needle biopsy was performed within fifteen days after CEUS. Twenty two tumors were finally diagnosed as moderately differentiated HCC, twelve as well differentiated HCC, and four as clear cell carcinomas using Edmondson Grade system. The enhancement patterns of different histopathological HCCs were analyzed. RESULTS: Before CEUS, only 16 lesions (42.1%) were diagnosed as malignant or possibly malignant. After CEUS, 38 HCCs were enhanced in different degrees following contrast administration,of which, all the 22 moderately differentiated HCCs presented typical "fast-in and fast-out" pattern with fast enhancement in arterial phase and then a quick wash-out in the parenchymal phase. Nine (75.0%) of the 12 well differentiated HCCs presented "fast-in and slow-out" pattern. One of the 4 clear cell carcinomas presented "fast-in and fast-out", one presented "fast-in and slow-out" and the other 2 presented "slightly slow-in and slow-out" pattern. According to the enhancement patterns, 76.3% (29 tumors) were considered as malignant, while 18.4% (7 tumors) as possibly malignant, only 5.3% (2 tumors smaller than 1.5 cm) could not be diagnosed by CEUS. CONCLUSION: The identification of different enhancement patterns of various histological types of small HCCs could improve the diagnostic ability of ultrasound in cirrhotic liver. CEUS might be also helpful in detecting small HCCs. Thus CEUS could be a complementary method of enhanced CT and other imaging methods in early diagnosis of HCCs.

Adolescent↗

MutH complexed with hemi- and unmethylated DNAs: coupling base recognition and DNA cleavage.

MutH initiates mismatch repair by nicking the transiently unmethylated daughter strand 5' to a GATC sequence. Here, we report crystal structures of MutH complexed with hemimethylated and unmethylated GATC substrates. Both structures contain two Ca2+ ions jointly coordinated by a conserved aspartate and the scissile phosphate, as observed in the restriction endonucleases BamHI and BglI. In the hemimethylated complexes, the active site is more compact and DNA cleavage is more efficient. The Lys residue in the conserved DEK motif coordinates the nucleophilic water in conjunction with the phosphate 3' to the scissile bond; the same Lys is also hydrogen bonded with a carbonyl oxygen in the DNA binding module. We propose that this Lys, which is conserved in many restriction endonucleases and is replaced by Glu or Gln in BamHI and BglII, is a sensor for DNA binding and the linchpin that couples base recognition and DNA cleavage.

Amino Acid Motifs↗

Inhibitory effect of ganglioside GD1b on K+ current in hippocampal neurons and its involvement in apoptosis suppression.

Gangliosides are endogenous membrane components enriched in neuronal cells. They have been shown to play regulatory roles in many cellular processes. Here, we show for the first time that ganglioside GD1b plays an antiapoptotic role in cultured hippocampal neurons. GD1b inhibited the voltage-dependent outward delayed rectifier current (I(K)) but not the transient outward A-type current in a dose-dependent manner, with an IC50 value of 15.2 microM. This effect appears to be somehow specific, because GD1b, but not GM1, GM2, GM3, GD1a, GD3, or GT1b, was effective in inhibiting I(K). Intracellular application of staurosporine (STS; 0.1 microM) resulted in rapid activation of I(K), which was partially reversed upon addition of the K+ channel blocker tetraethylammonium (TEA; 5 mM) and GD1b (10 microM). Furthermore, GD1b (10 microM) attenuated STS-induced neuronal apoptosis by nearly the same amount as 5 mM TEA. In addition, GD1b suppressed the apoptosis-associated caspase 3 activation that was activated by STS. Collectively, these findings suggest that GD1b plays an antiapoptotic role in cultured hippocampal neurons through its inhibitory effect on the I(K) and caspase activity.

Animals↗